Showing papers in "Journal of basic and clinical physiology and pharmacology in 2021"

Characterization of cardiac autonomic function in COVID-19 using heart rate variability: a hospital based preliminary observational study.

Abstract: OBJECTIVES: The novel corona virus disease, which was initially reported in China in late 2019, has become a global pandemic affecting 330 million cases. COVID-19 affects predominantly the respiratory system, in addition to other organ systems, mainly the cardiovascular system. One of the hypotheses is that virus entering the target cells by binding to angiotensin converting enzyme 2 affecting hypothalamic pituitary axis could lead to dysautonomia which is measured by heart rate variability (HRV). HRV is a non-invasive measure of autonomic function that facilitates identification of COVID-19 patients at the risk of developing cardiovascular complications. So, we aimed to assess HRV in COVID patients and compare between COVID patients and normal controls. METHODS: In a case control design, we compared 63 COVID-19 infected patients with 43 healthy controls matched for age and gender. Along with clinical characterization, heart rate variability was evaluated using ambulatory 5 min ECG in lead II and expressed in frequency and time domain measures. Statistical analysis was performed using SPSS 17.0. RESULTS: Mean age of the study population was 49.1 ± 14.2 years and 71 (66.9%) were males. Frequency domain measures high (HF) and low (LF) frequency powers were significantly decreased in COVID-19 patients compared to controls. HF/LF and LF/HF ratios were not different between groups. Time domain measures rMSSD (root mean square of successive RR interval differences) and SDNN (standard deviation of NN intervals) were significantly increased among COVID-19 subjects. COVID-19 infection was associated with increased parasympathetic activity as defined by rMSSD>40 {adjusted odds ratio 7.609 (95% CI 1.61-35.94); p=0.01} and SDNN>60 {adjusted odds ratio 2.620 (95% CI 1.070-6.44); p=0.035} after adjusting for age, gender and comorbidities. CONCLUSIONS: Our study results showed increased parasympathetic tone in COVID patients. Early diagnosis of autonomic imbalance in COVID patients is needed to plan management and limit progression of disease.

6-OHDA mediated neurotoxicity in SH-SY5Y cellular model of Parkinson disease suppressed by pretreatment with hesperidin through activating L-type calcium channels.

Abstract: Objectives Parkinson's disease (PD) is a neurological condition with selective progressive degeneration of dopaminergic neurons. Routine therapies are symptomatic and palliative. Although, hesperidin (Hsd) is known for its neuroprotective effects, its exact cellular mechanism is still a mystery. Considering the important role of calcium (Ca2+) in cellular mechanisms of neurodegenerative diseases, the present study aimed to investigate the possible effects of Hsd on Ca2+ channels in cellular model of PD and the possible association between the selective vulnerability of neurons in cellular models of PD and expression of the physiological phenotype that changes Ca2+ homeostasis. Methods SH-SY5Y cell line was used in this study; cell damage was induced by 150 µM 6-OHDA and the cells' viability was examined using MTT assay. Intracellular calcium, reactive oxygen species (ROS) and mitochondrial membrane potential were determined by the fluorescence spectrophotometry method. The expressions of calcium channel receptors were determined by gel electrophoresis and immunoblotting. Results Loss of cell viability and mitochondrial membrane potential were confirmed in 6-OHDA treated cells. In addition, intracellular ROS and calcium levels, calcium channel receptors significantly increased in 6-OHDA-treated cells. Incubation of SH-SY5Y cells with hesperidin showed a protective effect, reduced the biochemical markers of cell damage/death, and balanced calcium hemostasis. Conclusions Based on our findings, it seems that hesperidin could suppress the progression of the cellular model of PD via acting on intracellular calcium homeostasis. Further studies are needed to confirm the potential benefits of preventive and therapeutic effects of stabilizing cellular calcium homeostasis in neurodegenerative disease.

Moringa oleifera seed oil partially abrogates 2,3-dichlorovinyl dimethyl phosphate (Dichlorvos)-induced cardiac injury in rats: evidence for the role of oxidative stress.

Abstract: OBJECTIVES Cardiovascular diseases are major causes of non-infectious diseases globally. The use of pesticides has been linked with the high global burden of non-communicable diseases. Despite the indiscriminate exposure to dichlorvos (DDVP) by inhalation, no report exists on its possible cardiotoxic effect. This study investigated the cardiotoxicity of DDVP exposure by inhalation and the possible role of Moringa oleifera seed oil. METHODS Twenty-one male rats were randomly assigned into 3 groups. Group A (control) received only standard rat diet and water ad' libitum, group B (DDVP) was exposed to DDVP via inhalation for 15 min daily in addition to rat diet and water, and group C (DDVP + M. oleifera seed oil) received treatment as group B as well as 300 mg/kg of M. oleifera seed oil p.o for 28 days. RESULTS Significant reductions in body weight gain and cardiac weight were observed in DDVP-exposed animals (p<0.05). Similarly, 28 days of exposure to DDVP led to a significant increase in lactate dehydrogenase, creatinine kinase and troponin (p<0.05). DDVP-exposed rats also showed a significant increase in malondialdehyde, and a significant decline in superoxide dismutase and glutathione peroxidase (p<0.05). However, catalase was comparable in DDVP-exposed and control rats. Histopathological observations of the cardiac tissue revealed that DDVP caused marked fat degeneration and necrosis of the myocardial layer. The changes in DDVP-exposed rats were significantly, though not completely, restored by M. oleifera seed oil administration. CONCLUSIONS This study provides novel mechanistic information on the cardiotoxicity of DDVP inhalation, and the antioxidant potential of M. oleifera seed oil.

Update of hypothyroidism and its management in Unani medicine.

Abstract: Hypothyroidism is a clinical syndrome caused by thyroid hormone deficiency due to reduced production, deranged distribution, or lack of effects of thyroid hormone. The prevalence of hypothyroidism in developed countries is around 4-5%, whereas it is about 11% in India, only 2% in the UK, and 4·6% in the USA. It is more common in women than in men. Hypothyroidism has multiple etiologies and manifestations. The most common clinical manifestations are weight gain, loss of hair, cold intolerance, lethargy, constipation, dry skin, and change in voice. The signs and symptoms of hypothyroidism differ with age, gender, severity of condition, and some other factors. The diagnosis is based on clinical history, physical examination and serum level of FT3, FT4, and thyroid-stimulating hormone, imaging studies, procedures, and histological findings. The treatment of choice for hypothyroidism is levothyroxine, however; in this review article, we have discussed the epidemiology, etiology, clinical sign and symptoms, diagnosis, complications, and management of hypothyroidism in modern medicine and a comparative treatment by the Unani system of medicine (USM). In the USM, the main emphasis of the principle of treatment (Usool-e-Ilaj) is to correct the abnormal constitution (Su-e-Mizaj) and alter the six prerequisites for existence (Asbab-e-Sitta Zarooriya) to restore normal health. It is a packaged treatment, that is, different components of treatment are given as a package form which includes different drugs, dosages form, and regimens.

The complex relationship between physical activity and diabetes: an overview.

Abstract: Diabetes mellitus (DM) is a widespread condition, representing a challenging disease to manage. Exercise is being increasingly recommended as part of the therapeutic regimen for DM but the management of different forms of physical activity is difficult for individuals with diabetes, trainers, and physicians. Regular exercise can improve health and well-being, helping individuals to achieve their target lipid profile, body composition, cardio-respiratory fitness, and glycemic goals. People with diabetes tend to be as inactive as the general population, with a large percentage of individuals not achieving the minimum amount of recommended physical activity levels. Indeed, several barriers to exercise exist for persons with diabetes, including sports eligibility, multi-modality management of diabetic athletes, and inadequate knowledge about adequate type and intensity of exercise. The aim of the present review is to provide the current understanding of mechanisms, recommendations, and beneficial effects of different modalities of exercise for the treatment of DM.

Modulation of sleep using electrical vestibular nerve stimulation prior to sleep onset: a pilot study.

Abstract: OBJECTIVES Electrical stimulation of the vestibular system (VeNS) has been shown to improve Insomnia Severity Index (ISI) when delivered during sleep. We hypothesize that repeated electrical vestibular stimulation, when delivered prior to sleep onset, will improve ISI scores. The primary aim of this study was to assess the effect that VeNS had on ISI scores when delivered prior to sleep onset. A secondary aim was to provide initial data indicating "length of time to effect" that will allow more appropriate design of a larger randomized control trial (RCT). METHODS The present study was an experimental study (pre and post without control). The participants acted as self-controls. After recording the baseline values, electrical vestibular nerve stimulation was administered as intervention once in a day for 30 min, 1 h prior to sleep onset using ML1000 device (Neurovalens, UK) for 14 days. RESULTS There was significant decrease in the ISI scores followed by the electrical vestibular nerve stimulation. Further, participants reported a significant increase in well-rested sleep post the intervention period. CONCLUSIONS This study supports our hypothesis that VeNS has a positive impact on ISI scores when delivered on a regular basis prior to sleep onset.

Evidence that Ginkgo Biloba could use in the influenza and coronavirus COVID-19 infections.

Abstract: Coronavirus COVID-19 pandemic invades the world. Public health evaluates the incidence of infections and death, which should be reduced and need desperately quarantines for infected individuals. This article review refers to the roles of Ginkgo Biloba to reduce the risk of infection in the respiratory tract, the details on the epidemiology of corona COVID-19 and influenza, and it highlights how the Ginko Biloba could have been used as a novel treatment.Ginkgo Biloba can reduce the risk of infection by several mechanisms; these mechanisms involve Ginkgo Biloba contains quercetin and other constituents, which have anti-inflammatory and immune modulator effects by reducing pro-inflammatory cytokines concentrations. Cytokines cause inflammation which have been induced the injuries in lung lining.Some observational studies confirmed that Ginkgo Biloba reduced the risk of asthma, sepsis and another respiratory disease as well as it reduced the risk of cigarette smoking on respiratory symptoms. While other evidences suggested the characters of Ginkgo Biloba as an antivirus agent through several mechanisms. Ginkgolic acid (GA) can inhibit the fusion and synthesis of viral proteins, thus, it inhibit the Herpes Simplex Virus type1 (HSV-1), genome replication in Human Cytomegalovirus (HCMV) and the infections of the Zika Virus (ZIKV). Also, it inhibits the wide spectrum of fusion by inhibiting the three types of proteins that have been induced fusion as (Influenza A Virus [IAV], Epstein Barr Virus [EBV], HIV and Ebola Virus [EBOV]).The secondary mechanism of GA targeting inhibition of the DNA and protein synthesis in virus, greatly have been related to its strong effects, even afterward the beginning of the infection, therefore, it potentially treats the acute viral contaminations like (Measles and Coronavirus COVID-19). Additionally, it has been used topically as an effective agent on vigorous lesions including (varicella-zoster virus [VZV], HSV-1 and HSV-2). Ginkgo Biloba may be useful for treating the infected people with coronavirus COVID-19 through its beneficial effect. To assess those recommendations should be conducted with random control trials and extensive population studies.

Predicting the molecular mechanism of glucosamine in accelerating bone defect repair by stimulating osteogenic proteins.

Abstract: Objectives Bone defect is serious condition that is usually caused by traffic accident. Chitosan is a polymer developed as a scaffold to treat bone defect. However, the mechanism by which chitosan can accelerate bone growth in defect area is still unclear. This study aims to identify proteins which are crucial to the osteogenic properties of chitosan monomer using an in silico study. Methods Molecular docking was carried out on chitosan monomer, which are d-glucosamine and glucosamine 6-phosphate units against bone morphogenetic protein 2 (BMP-2), fibronectin, fibroblast growth factor (Fgf), and phosphate transporter (PiT) using AutoDock Vina. Ligand preparation was carried out using Chem3D version 15.0.0.106, while protein preparation was performed using AutoDockTools version 1.5.6. Results The results showed that glucosamine 6-phosphate had the best binding affinity with fibronectin and PiT, which was -5.7 kcal mol-1 on both proteins, while d-glucosamine had the best binding affinity with PiT (-5.2 kcal mol-1). Conclusions This study suggests that the osteogenic properties of chitosan may be due to the presence of bonds between glucosamine units and fibronectin and/or PiT. However, in vitro studies need to be done to prove this.

Correlation between biofilm formation and antimicrobial susceptibility pattern toward extended spectrum β-lactamase (ESBL)- and non-ESBL-producing uropathogenic bacteria.

Abstract: Background Urinary tract infections (UTIs) are the most common bacterial infection encountered worldwide and are associated with significant morbidity and mortality. Methods The present study was undertaken to investigate the biofilm-forming ability, antibiotic susceptibility patterns and extended spectrum β-lactamase (ESBL) production of seven uropathogenic isolates comprising both Escherichia coli and Klebsiella pneumoniae. The morphological, cultural and biochemical tests for the identification of the isolates, antibiotic susceptibility test, detection of ESBL production, biofilm formation on 96-well microtiter plate and Congo red agar (CRA) media are performed. Results The antimicrobial susceptibility profiles obtained in this study showed that the most active drugs gentamicin, amikacin and imipenem (100% sensitivity) were followed by amoxicillin-clavulanic acid (85% sensitivity), co-trimoxazole, ciprofloxacin (57% sensitivity) ceftazidime and kanamycin (50% sensitivity). All the isolates showed resistance to amoxicillin followed by ceftriaxone and cefotaxime (71% resistance), and the scenario gets more complicated because of the production of ESBL by five isolates (three E. coli isolates and two K. pneumoniae). The strains were also able to form biofilm as tested on CRA medium and by microtiter plate assay. The correlation between ESBL, non-ESBL and biofilm-producing E. coli and K. pneumonia was determined along with the multiple drug resistance patterns of E. coli and K. pneumonia. Conclusions The findings of the study indicate that the emergence and rapid spread of such multidrug-resistant pathogens are of great concern. Early detection of ESBL-producing pathogen is of paramount clinical importance; therefore, strict infection control practices as well as therapeutic guidance for confirmed infection can be rapidly initiated.

Caffeic and chlorogenic acids modulate altered activity of key enzymes linked to hypertension in cyclosporine-induced hypertensive rats.

Abstract: OBJECTIVES This study aimed to explore the protective mechanism of caffeic acid (CAA) and chlorogenic acid (CHA) on cyclosporine (CSA) induced hypertensive rats. METHODS Effect of CAA and CHA on diastolic blood pressure (DBP), mean arterial pressure (MAP), angiotensin-converting enzyme (ACE), e-nucleotide triphosphate dephosphorylase (e-NTPDase), 5' nucleotidase and adenosine deaminase (ADA) activity in CSA-induced hypertensive rats were determined. RESULTS CAA and CHA administration stabilized hypertensive effect caused by CSA administration. Also, altered activity of ACE (lung), e-NTPDase, 5' nucleotidase, ADA as well as elevated malondiadehyde (MDA) level was restored in all the treated hypertensive rats in comparison with the untreated hypertensive rats. CONCLUSION Hence, these observed results could underlie some of the mechanisms through which CAA and CHA could offer antihypertensive effect.

Effects of date seeds administration on anxiety and depressive symptoms in streptozotocin-induced diabetic rats: biochemical and behavioral evidences.

Abstract: OBJECTIVES Several epidemiological data indicate that chronic hyperglycemia is associated with behavioral changes such as anxiety and depressive symptoms. Date seeds, one of the most potent products with potential antioxidant activities and possess many benefits against hyperglycemia and its complication. The aim of the current study was to explore the potential effect of date seeds extract on biochemical and behavioral changes (anxiety and depression) in streptozotocin (STZ)-diabetic rats. METHODS Rats were divided into four groups as follows: normal control, diabetic control, diabetic treated with the lyophilized aqueous extract of the date seed (2,000 mg/kg) (LAE-DS) and diabetics treated with insulin (4 UI/day). Experimental diabetes was induced by a single intraperitoneal injection of STZ (60 mg/kg). After 24 days treatment period, anxiety and depressive behaviors were evaluated using four behavioral tests. After sacrifice, blood samples were collected to evaluate lipid parameters. In addition, rat organs (kidney, liver and brain) were dissected out in order to estimate lipid peroxidation levels as oxidative stress marker. RESULTS Oral administration of the lyophilized aqueous extract of date seeds and insulin injection for 30 days significantly decreased blood glucose levels in STZ-diabetic rats and protected them against undesirable changes in lipid parameters, including cholesterol, triglycerides, LDL cholesterol, VLDL cholesterol and atherosclerosis index. Compared to untreated diabetic rat, a significant decrease in lipid peroxidation levels in kidney, liver and brain (Hippocampus and prefrontal cortex) were observed after treatment with insulin or LAE-DS in diabetic rats. Furthermore, insulin and LAE-DS administration prevented anxiety-related behaviors in STZ-diabetic rats. CONCLUSIONS Therefore, it would be possible to combine this extract with insulin and use it as an antioxidant supplement for type 1 diabetic patients.

Fabrication and characterization of bovine hydroxyapatite-gelatin-alendronate scaffold cross-linked by glutaraldehyde for bone regeneration.

Abstract: Objectives Alendronate are widely used in the treatment of bone disorders characterized by inhibit osteoclast-mediated bone resorption such as Paget's disease, fibrous dysplasia, myeloma, bone metastases and osteoporosis. In recent studies alendronate improves proliferation and differentiation of osteoblasts, thereby facilitating for bone regeneration. The disadvantages of this class are their poor bioavailability and side effects on oral and intravenous application such as stomach irritation and osteonecrosis in jaw. Thus, local treatment of alendronate is needed in order to achieve high concentration of drug. Bovine hydroxyapatite-gelatin scaffold with alendronate was studied. Glutaraldehyde was used as cross-linking agent, increase the characteristics of this scaffold. The objectives of this study were to manufacture and characterize alendronate scaffold using bovine hydroxyapatite-gelatin and crosslinked by glutaraldehyde. Methods Preparation of cross-linked bovine hydroxyapatite-gelatin and alendronate scaffold with different concentration of glutaraldehyde (0.00, 0.50, 0.75, and 1.00%). The scaffolds were characterized for compressive strength, porosity, density, swelling ratio, in vitro degradation, and cytotoxicity (the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assay, shorted as MTT assay). Results Bovine hydroxyapatite-gelatin-alendronate scaffold cross-linked with glutaraldehyde showed lower density than without glutaraldehyde. As glutaraldehyde concentration increased, porosity also increased. Eventually, it reduced compressive strength. Swelling ratio and in vitro degradation was negatively dependent on glutaraldehyde concentration. In addition, the scaffold has a good safety by MTT assay. Conclusions Bovine hydroxyapatite-gelatin-alendronate scaffold was fabricated with various concentrations of glutaraldehyde. The presence of glutaraldehyde on bovine hydroxyapatite-gelatin-alendronate is safe and suitable candidate scaffold for bone regeneration.

Pharmacological investigations on efficacy of Phlorizin a sodium-glucose co-transporter (SGLT) inhibitor in mouse model of intracerebroventricular streptozotocin induced dementia of AD type.

Abstract: Objectives The study has been commenced to discover the potential of Phlorizin (dual SGLT inhibitor) in streptozotocin induced dementia of Alzheimer's disease (AD) type. Material and methods Injection of Streptozotocin (STZ) was given via i.c.v. route (3 mg/kg) to induce dementia of Alzheimer's type. In these animals learning and memory was evaluated using Morris water maze (MWM) test. Glutathione (GSH) and thiobarbituric acid reactive species (TBARS) level was quantified to evaluate the oxidative stress; cholinergic activity of brain was estimated in term of acetylcholinesterase (AChE) activity; and the levels of myeloperoxidase (MPO) were measured as inflammation marker. Results The mice model had decreased performance in MWM, representing impairment of cognitive functions. Biochemical evaluation showed rise in TBARS level, MPO and AChE activity, and fall in GSH level. The histopathological study revealed severe infiltration of neutrophils. In the study, Phlorizin/Donepezil (serving as positive control) treatment mitigate streptozotocin induced cognitive decline, histopathological changes and biochemical alterations. Conclusions The results suggest that Phlorizin decreased cognitive function via its anticholinesterase, antioxidative, antiinflammatory effects and probably through SGLT inhibitory action. It can be conferred that SGLTs can be an encouraging target for the treatment of dementia of AD.

In silico approach: docking study of oxindole derivatives against the main protease of COVID-19 and its comparison with existing therapeutic agents.

Abstract: Objectives Presently, the pandemic of COVID-19 has worsened the situation worldwide and received global attention. The United States of America have the highest numbers of a patient infected by this disease followed by Brazil, Russia, India and many other countries. Moreover, lots of research is going on to find out effective vaccines or medicine, but still, no potent vaccine or drug is discovered to cure COVID-19. As a consequence, many types of research have designated that computer-based studies, such as protein-ligand interactions, structural dynamics, and chembio modeling are the finest choice due to its low cost and time-saving features. Here, oxindole derivatives have been chosen for docking because of their immense pharmacological applications like antiviral, antidiabetic, anti-inflammatory, and so on. Molecular docking of 30 oxindole derivatives done on the crystallized structure of the protein (COVID-19 Mpro). Methods The process of docking, interaction, and binding the structure of ligand with protein has executed using Molegro Virtual Docker v.7.0.0 (MVD) and visualized the usage by Molegro Molecular Viewer v.7.0.0 (MMV). Results Among the 30 derivatives, the outcomes depicted better steric interaction and hydrogen bonding amongst OD-22 ligand, OD-16 ligand, OD-4 ligand, and OD-9 ligand (oxindole derivatives) with COVID-19. In addition to this, the comparative study of these four compounds with existing drugs that are under clinical trials shows comparatively good results in terms of its MolDock scores, H-bonding and steric interactions. Conclusions Hence, It is proposed that these four oxindole derivatives have good potential as a new drug against coronavirus as possible therapeutic agents.

The impact of glutaraldehyde on the characteristics of bovine hydroxyapatite-gelatin based bone scaffold as gentamicin delivery system.

Abstract: Objectives Biomaterials are widely used as drug delivery systems targeting bone tissue, such as to treat bone infectious disease. However, the addition of drugs to biomaterials weakens their mechanical properties. Crosslinkers are compounds that improve the mechanical properties of biomaterials. This study aims to determine the effect of glutaraldehyde (GTA) as a crosslinker on the characteristics of bovine hydroxyapatite-gelatin-based bone scaffold with gentamicin as antibiotics (BHA-GEL-GEN-GTA). Methods BHA-GEL-GEN-GTA scaffold with GTA solid content ranging from 0.1 to 1.4 wt% was made by direct compression. The compressive strength test was carried out using autograph. Scaffold degradation test was carried out by dissolving the scaffolds in PBS. Scaffold toxicity was performed by MTT assay using BHK-21 fibroblast cells. Results There was a significant difference in the scaffolds' compressive strength due to differences in GTA volume. Scaffold crosslinked using GTA with solid content 0.1 and 0.2 wt% in 2 mL solution had higher compressive strength than those in 1 mL solution. Furthermore, GTA with solid content 0.6, 1, 1.2, and 1.4 wt% showed higher compressive strength than those without GTA. Degradation test results showed that GTA increased the percentage of weight loss and swelling of the scaffold. The scaffold exhibited a nontoxic profile in MTT assay. Conclusions GTA with optimum solid content shows great compressive strength, stable swelling profile with low percentage of scaffold's weight loss, and is considered as nontoxic.

The effects of quercetin on the expression of SREBP-1c mRNA in high-fat diet-induced NAFLD in mice

Abstract: Objectives The study aimed to determine the effect of quercetin on the expression of primary regulator gene involved in lipogenesis and triglycerides synthesis in the liver, and the sterol regulatory binding protein-1c (SREBP-1c) mRNA in non-alcoholic fatty liver disease (NAFLD) with a high-fat diet (HFD) model. Methods Fifty-six Balb/c mice were divided into seven groups: standard feed; HFD; HFD and quercetin 50 mg/kg for 28 days; HFD and quercetin 100 mg/kg BW for 28 days; HFD and quercetin 50 mg/kg for 14 days; HFD and quercetin 100 mg/kg for 14 days; HFD and repaired fed for 14 days. Quercetin was administered intraperitoneally. The animals were sacrificed 24 h after the last treatment; the liver was taken for macroscopic, histopathological staining using hematoxylin-eosin and reverse transcription-PCR analysis sample. Results HFD significantly increased the expression of SREBP-1c mRNA; meanwhile, quercetin and repaired feed significantly reduced the expression of SREBP-1c mRNA in the liver. Quercetin at a dose of 50 mg/kg and 100 mg/kg also improved liver cells' pathological profile in high-fat diet NAFLD. Conclusions The present study suggests that quercetin has an inhibitory effect on SREBP-1c expression and improved liver pathology in NAFLD mice.

Apelin-13 protects human neuroblastoma SH-SY5Y cells against amyloid-beta induced neurotoxicity: Involvement of anti oxidant and anti apoptotic properties.

Abstract: OBJECTIVES We investigated the effect of apelin-13 on the cellular model of AD, amyloid-β (Aβ) treated SH-SY5Y cells in rats. METHODS The SH-SY5Y cells were pretreated with different doses of apelin-13 (1, 2.5, 5, and 10 μg/mL), half an hour before adding 50% Aβ treatment. After 24 h, cells were evaluated for survival, oxidative stress, mitochondrial calcium release, caspase-3, and cytochrome c levels, compared to control group (beta-actin). Statistical analysis was performed by SPSS 16. RESULTS Apelin-13 at the dose of 2.5 μg/mL protected against IC50 Aβ (p<0.001). Apelin-13 at doses of 1, 2.5, and 5 μg/mL showed protective effects against the reactive oxygen species (ROS) produced by Aβ (p<0.001). Apelin-13 at doses of 2.5 and 5 μg/mL reduced calcium release, caspase-3, and cytochrome c (all p<0.001). CONCLUSIONS Apelin-13 prevented apoptosis, oxidative stress, and mitochondrial toxicity and can be a suitable option for treatment of AD. The appropriate treatment strategy for humans has to be investigated in future studies.

COVID-19 disease in clinical setting: impact on gonadal function, transmission risk, and sperm quality in young males.

Abstract: Objectives We want to evaluate the possible presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in semen samples and semen quality, looking for a possible relationship between the infectious disease and fertility. Methods In this prospective study, we enrolled 15 consecutive men (age 18-50 years) with positive oropharyngeal swab to SARS-CoV-2 and classified, according to WHO criteria, in mild to moderate disease. A semen sample was collected to detect SARS-CoV viral RNA by the automated Real-Time PCR ELITe InGenius® system and the GeneFinderTM COVID-19 Plus RealAmp Kit assay (ELITechGroup, France). Analysis of semen characteristics was performed according to WHO laboratory manual 5th ed. for the examination and processing of human semen. Blood samples for the dosage of hormonal assay, procalcitonin, interleukin 6, C-reactive protein were obtained. Results SARS-CoV-2 RNA has not been detected in semen samples from any of the subjects analysed. Sperm analysis exhibited abnormal seminal values in 14 out of 15 patients (93.3%). Furthermore, no difference was detected regarding sperm quality between mild and moderate SARS-CoV-2 patients. No alteration in the inflammatory indices was observed in the studied population, as well gonadotropins and testosterone levels. Conclusions COVID patients studied exhibits alteration of the seminal fluid both in microscopic and macroscopic characteristics such as hypoposia and increased viscosity, which have not been detected in previous studies. The presence of viral RNA within the seminal fluid was excluded.

Heart rate variability during cardiovascular reflex testing: the importance of underlying heart rate.

Abstract: OBJECTIVES Heart rate variability (HRV) is often measured during clinical and experimental cardiovascular reflex tests (CRT), as a reflection of cardiac autonomic modulation, despite limited characterization of the rapid responses that occur. Therefore, we evaluated the responsiveness of HRV indices in 20 healthy young adults (age, 27 ± 6 y; mass, 76.9 ± 16.8 kg; height, 1.79 ± 0.12 m) during four separate established CRT. METHODS These included the [I] orthostatic challenge, [II] isometric handgrip, [III] cold pressor and [IV] cold diving reflex tests. Electrocardiogram was recorded throughout, with HRV derived from RR intervals at rest and from each CRT. On a separate day, a subgroup of participants (n=9) completed the same protocol for a second time. RESULTS The maximal slope of heart rate change (dTdt) was significantly different between all CRT, with the orthostatic challenge producing the fastest increase (2.56 ± 0.48) and the cold pressor the fastest reduction (-1.93 ± 0.68) in heart rate. Overall HRV, reflected by Poincare plot ratio (SD1:SD2), was significantly reduced during all CRT ([I], -0.41 ± 0.12; [II], -0.19 ± 0.05; [III], -0.36 ± 0.12; [IV], -0.44 ± 0.11; p<0.05) relative to baseline and this was reproducible in time-series. However, when HRV indices were correlated to mean-RR an exponential growth-like relationship was evident (R2 ranging from: 0.52-0.62). CONCLUSIONS These unique outcomes demonstrate that short-term alterations in HRV are evident during CRT, while indicating the importance of adjusting for, or at least reporting, underlying heart rate when interpreting such measures.

Nitric oxide mediates the antidepressant-like effect of modafinil in mouse forced swimming and tail suspension tests.

Abstract: Objectives Previous studies have suggested antidepressant properties for modafinil; however, the underlying mechanisms mediating the antidepressant effect of modafinil have not been well recognized in clinical and animal studies. Nitric oxide (NO) is involved in the pathophysiology of depression. We attempted to investigate the possible role of NO in the antidepressant-like effect of modafinil in mouse forced swimming test (FST) and tail suspension test (TST). Methods The antidepressant-like effect of modafinil (25, 50 and 75 mg/kg), alone and in combination with l-arginine, l-arg, (100 mg/kg) and NG-l-arginine methyl ester, l-NAME (5 mg/kg), was evaluated using FST and TST. Following behavioral tests, the hippocampi were dissected out to measure nitrite levels. Results Findings suggested that administration of modafinil at doses of 50 and 75 mg/kg significantly reduced immobility time in the FST and TST. Furthermore, administration of l-arg and l-NAME increased and decreased, respectively, the immobility time in the FST and TST. We showed that co-administration of a sub-effective dose of modafinil (25 mg/kg) plus l-NAME potentiated the antidepressant-like effect of the sub-effective dose of modafinil. In addition, co-treatment of an effective dose of modafinil (75 mg/kg) with l-arg attenuated the antidepressant-like effect of the effective dose of modafinil. We showed that the antidepressant-like effect of modafinil is associated with decreased nitrite levels in the hippocampus. Conclusions Our findings for the first time support that the modulation of NO, partially at least, is involved in the antidepressant-like effect of modafinil in mouse FST and TST.

Correlation between the exposure time to mobile devices and the prevalence of evaporative dry eyes as one of the symptoms of computer vision syndrome among Senior High School students in East Java, Indonesia.

Abstract: Objectives Computer vision syndrome (CVS) is a group of various eye and vision-related problems from prolonged use of mobile devices. Symptoms include dry eyes, blurred vision, eye strain, headache, and also neck and shoulder pain. This study was carried out to analyze the correlation between the exposure time of High Energy Visible (HEV) from mobile devices' use and the prevalence of evaporative dry eyes in young age. Methods An observational cross-sectional study was done using quota sampling method for 100 High School students. Data collection was performed using questionnaire to identify daily use of mobile devices (hours) and duration for using mobile devices (years). A classification was determined as mild, moderate, and heavy HEV exposure. Evaporative dry eyes were diagnosed using tear break-up time test (TBUT) of less than 10 s for both eyes. Results Ninety-four students participated in this study. A total of 82 students (87.2%) experienced evaporative dry eyes. There were 11 students (11.7%) who had dry eyes with mild exposure, 18 students (19.1%) had dry eyes with moderate exposure, and 53 students (56.4%) had dry eyes with heavy exposure. A chi square analysis showed all HEV exposures have similar risk to the prevalence of dry eyes among High School students (p Conclusions The risk of developing evaporative dry eyes, as one of the symptoms of CVS in young age with normal tear production, could be induced even with minimal exposure to mobile devices.

Evaluation of heart rate variability, blood pressure and lipid profile alterations from dual transceiver mobile phone radiation exposure.

Abstract: Objectives Electromagnetic fields have been reported to alter electrical activities in the brain and heart. However, there is paucity of information on the potential functional alterations that magnetic fields from mobile phone could cause to the heart. This study investigated heart rate variability (HRV), blood pressure (BP) and lipid profile in Wistar rats exposed to electromagnetic field radiation from a dual transceiver mobile phone (DTrMP). Methods Twenty-one male albino Wistar rats (140-180 g) were randomly assigned to two major groups positioned 5 m apart as follows: control: no phone (n=7) and treatment group (n=14) continuously exposed to electromagnetic field from Tecno T312 DTrMP 900/1800 MHz set in silence mode. Experimental treatment consisted in 10 min calls/day, directed to this device for a period of six weeks. Seven animals from the treatment group were allowed to recover for a period of two weeks after exposure. HRV, systolic, diastolic and mean arterial BP were noninvasively investigated, while serum lipid profile and heart tissue nitric oxide (NO) activities were determined using standard procedures. Results There was significant (p<0.05) increase in systolic, diastolic, mean arterial BP and a decrease in HRV. Serum high density lipoproteins decreased, while total cholesterol, atherogenic indices, and heart NO levels increased significantly in the radiation exposed animals. The alterations observed in exposed animals remained unchanged even after the recovery period. Conclusions These results suggest that exposure to electromagnetic radiation from dual transceiver mobile phones could be a risk factor to increase in blood pressure.

Pathophysiological effects of cadmium(II) on human health-a critical review.

Abstract: Cadmium(II) is an omnipresent environmental toxicant emitted from various industrial sources and by anthropogenic sources such as smoking. Cadmium(II) enters our body through various sources including contaminated food and drinks and from active or passive smoking. It spares no organs in our body and the calamities it invites include primarily nephrotoxicity, osteotoxicity, teratogenicity, endocrine disruption, hepatotoxicity and carcinogenicity above all. It brings about a bolt from the blue in the cellular biochemistry by generating reactive oxygen species (ROS), disrupting the factors involved in the repair of DNA lesions and many other toxic nuisances otherwise by modulating the cell signalling machinery and acting as a potent carcinogen above all. In this review, we have tried to decipher some of the mechanisms played by cadmium(II) in exhibiting its toxic effects on various system of our body.

Paradoxical sleep deprivation induces oxidative stress in the submandibular glands of Wistar rats.

Abstract: Objectives Paradoxical sleep deprivation has been associated with impaired salivary secretion in rats. However, the mechanism that underlies this is not known. Therefore, this study assessed salivary and serum oxidative stress levels following paradoxical sleep deprivation in rats. Methods Twenty-one male Wistar rats randomly divided into three groups of seven rats each as; Control (C); partial sleep-deprived (PSD); and total sleep-deprived (TSD) were used. Malondialdehyde (MDA) concentration, Superoxide dismutase (SOD), and catalase activities were evaluated in saliva, serum, and submandibular glands after seven days of sleep deprivation. Data were expressed as mean ± standard error of the mean and analyzed using one-way ANOVA, Tukey HSD post hoc, and Pearson's correlation tests. Results Serum MDA levels were significantly higher in both the TSD and PSD groups compared to the control group whereas only the TSD group showed higher submandibular MDA levels compared to the PSD group and the control group. Submandibular SOD activity was significantly lower in both the TSD and PSD groups compared to the control group. Serum catalase activity was significantly lower in the TSD group only compared to the control group. Conclusions These results have demonstrated for the first time that paradoxical sleep deprivation was associated with changes in the oxidant/antioxidant defense system in the submandibular salivary glands of male Wistar rats which may contribute to impairment in salivary secretion.

Conditioned medium from the human umbilical cord-mesenchymal stem cells stimulate the proliferation of human keratinocytes.

Abstract: Objectives Wound healing is a complex process with a sequence of restoring and inhibition events such as cell proliferation, differentiation, migration as well as adhesion. Mesenchymal stem cells (MSC) derived conditioned medium (CM) has potent therapeutic functions and promotes cell proliferation, anti-oxidant, immunosuppressive, and anti-apoptotic effects. The main aim of this research is to study the role of human umbilical cord-mesenchymal stem cells (UC-MSCs) derived CM in stimulating the proliferation of human keratinocytes (HaCaT). Methods Firstly, MSC were isolated from human umbilical cords (UC) and the cells were then cultured in proliferative medium. We prepared and collected the CM after 72 h. Morphological changes were observed after the treatment of HaCaT cells with CM. To validate the findings, proliferation rate, clonal efficiency and also gene expression studies were performed. Results Increased proliferation rate was observed and confirmed with the expression of Proliferating Cell Nuclear Antigen (PCNA) after treatment with HaCaT cells. Cell-cell strap formation was also observed when HaCaT cells were treated with CM for a period of 5-6 days which was confirmed by the increased expression of Collagen Type 1 Alpha 1 chain (Col1A1). Conclusions Our results from present study depicts that the secretory components in the CM might play a significant role by interacting with keratinocytes to promote proliferation and migration. Thus, the CM stimulates cellular proliferation, epithelialization and migration of skin cells which might be the future promising application in wound healing.

Intracellular signaling molecules of nerve tissue progenitors as pharmacological targets for treatment of ethanol-induced neurodegeneration.

Abstract: Objectives The development of approaches to the treatment of neurodegenerative diseases caused by alcohol abuse by targeted pharmacological regulation of intracellular signaling transduction of progenitor cells of nerve tissue is promising We studied peculiarities of participation of NF-кB-, сАМР/РКА-, JAKs/STAT3-, ERK1/2-, p38-pathways in the regulation of neural stem cells (NSC) and neuronal-committed progenitors (NCP) in the simulation of ethanol-induced neurodegeneration in vitro and in vivo Methods In vitro, the role of signaling molecules (NF-кB, сАМР, РКА, JAKs, STAT3, ERK1/2, p38) in realizing the growth potential of neural stem cells (NSC) and neuronal-committed progenitors (NCP) in ethanol-induced neurodegeneration modeled in vitro and in vivo was studied To do this, the method of the pharmacological blockade with the use of selective inhibitors of individual signaling molecules was used Results Several of fundamental differences in the role of certain intracellular signaling molecules (SM) in proliferation and specialization of NSC and NCP have been revealed It has been shown that the effect of ethanol on progenitors is accompanied by the formation of a qualitatively new pattern of signaling pathways Data have been obtained on the possibility of stimulation of nerve tissue regeneration in ethanol-induced neurodegeneration by NF-кB and STAT3 inhibitors It has been found that the blockage of these SM stimulates NSC and NCP in conditions of ethanol intoxication and does not have a «negative» effect on the realization of the growth potential of intact progenitors (which will appear de novo during therapy) Conclusions The results may serve as a basis for the development of fundamentally new drugs to the treatment of alcoholic encephalopathy and other diseases of the central nervous system associated with alcohol abuse

Molecular docking studies of Nigella sativa L and Curcuma xanthorrhiza Roxb secondary metabolites against histamine N-methyltransferase with their ADMET prediction.

Abstract: Objectives Histamine N-methyltransferase (HNMT) is an enzyme that plays a crucial role in the inactivation of histamine in central nervous system, kidneys and bronchi. Inhibition of HNMT is known to have a potential role in treating attention-deficit hyperactivity disorder, memory impairment, mental illness and neurodegenerative illnesses. Therefore, to find potential compounds that could be developed as novel HNMT inhibitors, this study conducted an in silico study of the secondary metabolites of Nigella sativa L and Curcuma xanthorrhiza Roxb. Methods In this study, we conducted a molecular docking study of 36 secondary metabolites of N. sativa L and 26 secondary metabolites of C. xanthorrhiza Roxb using an in silico approach targeting HNMT protein (PDB ID: 2AOT) using AutoDockVina software. The prediction of ADMET characteristics was done using the pkCSM Online Tool. Results This study obtained one metabolite from N. sativa L (longifolene) and seven metabolites from C. xanthorrhiza Roxb {(+)-beta-atlantone, humulene epoxide, (-)-beta-curcumene, (E)-caryophyllene, germacrone, (R)-(-)-xanthorrhizol, and (-)-beta-caryophyllene epoxide} which were predicted to have potential to be developed as HNMT inhibitors. Conclusions This study found several secondary metabolites of N. sativa L and C. xanthorrhiza Roxb which had activity as HNMT inhibitors. This research can likewise be utilized as a basis for further research, both in vitro, in vivo, and clinical trials related to the development of secondary metabolites from N. sativa L and C. xanthorrhiza Roxb as novel HNMT inhibitor compounds.

Climate change and declining fertility rate in Malaysia: the possible connexions.

Abstract: Climate change is an incessant global phenomenon and has turned contentious in the present century. Malaysia, a developing Asian country, has also undergone significant vicissitudes in climate, which has been projected with significant deviations in forthcoming decades. As per the available studies, climate changes may impact on the fertility, either via direct effects on the gonadal functions and neuroendocrine regulations or via several indirect effects on health, socioeconomic status, demeaning the quality of food and water. Malaysia is already observing a declining trend in the Total fertility rate (TFR) over the past few decades and is currently recorded below the replacement level of 2.1 which is insufficient to replace the present population. Moreover, climate changes reportedly play a role in the emergence and cessation of various infectious diseases. Besides its immediate effects, the long-term effects on health and fertility await to be unveiled. Despite the huge magnitude of the repercussion of climate changes in Malaysia, research that can explain the exact cause of the present reduction in fertility parameters in Malaysia or any measures to preserve the national population is surprisingly very scarce. Thus, the present review aims to elucidate the possible missing links by which climate changes are impairing fertility status in Malaysia.