The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway was discovered more than a quarter-century ago. As a fulcrum of many vital cellular processes, the JAK/STAT pathway constitutes a rapid membrane-to-nucleus signaling module and induces the expression of various critical mediators of cancer and inflammation. Growing evidence suggests that dysregulation of the JAK/STAT pathway is associated with various cancers and autoimmune diseases. In this review, we discuss the current knowledge about the composition, activation, and regulation of the JAK/STAT pathway. Moreover, we highlight the role of the JAK/STAT pathway and its inhibitors in various diseases.

The JAK/STAT signaling pathway: from bench to clinic.

Pathological pain can be initiated after inflammation and/or peripheral nerve injury. It is a consequence of the pathological functioning of the nervous system rather than only a symptom. In fact, pain is a significant social, health, and economic burden worldwide. Flavonoids are plant derivative compounds easily found in several fruits and vegetables and consumed in the daily food intake. Flavonoids vary in terms of classes, and while structurally unique, they share a basic structure formed by three rings, known as the flavan nucleus. Structural differences can be found in the pattern of substitution in one of these rings. The hydroxyl group (-OH) position in one of the rings determines the mechanisms of action of the flavonoids and reveals a complex multifunctional activity. Flavonoids have been widely used for their antioxidant, analgesic, and anti-inflammatory effects along with safe preclinical and clinical profiles. In this review, we discuss the preclinical and clinical evidence on the analgesic and anti-inflammatory proprieties of flavonoids. We also focus on how the development of formulations containing flavonoids, along with the understanding of their structure-activity relationship, can be harnessed to identify novel flavonoid-based therapies to treat pathological pain and inflammation.

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Therapeutic Potential of Flavonoids in Pain and Inflammation: Mechanisms of Action, Pre-Clinical and Clinical Data, and Pharmaceutical Development.

Catechin, the name of which is derived from catechu of the extract of Acacia catechu L [...].

https://www.mdpi.com/1420-3049/24/3/528/pdf

Catechin in Human Health and Disease

Neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS), currently affect more than 6 million people in the United States. Unfortunately, there are no treatments that slow or prevent disease development and progression. Regardless of the underlying cause of the disorder, age is the strongest risk factor for developing these maladies, suggesting that changes that occur in the aging brain put it at increased risk for neurodegenerative disease development. Moreover, since there are a number of different changes that occur in the aging brain, it is unlikely that targeting a single change is going to be effective for disease treatment. Thus, compounds that have multiple biological activities that can impact the various age-associated changes in the brain that contribute to neurodegenerative disease development and progression are needed. The plant-derived flavonoids have a wide range of activities that could make them particularly effective for blocking the age-associated toxicity pathways associated with neurodegenerative diseases. In this review, the evidence for beneficial effects of multiple flavonoids in models of AD, PD, HD, and ALS is presented and common mechanisms of action are identified. Overall, the preclinical data strongly support further investigation of specific flavonoids for the treatment of neurodegenerative diseases.

https://www.mdpi.com/1422-0067/20/12/3056/pdf

The Potential of Flavonoids for the Treatment of Neurodegenerative Diseases

Japanese matcha is a type of powdered green tea, grown in a traditional way. Shading of the plants during the growth period enhances the processes of synthesis and accumulation of biologically active compounds, including theanine, caffeine, chlorophyll and various types of catechins. Green tea contains four main catechins, i.e., (−)-epicatechin (EC), (−)-epicatechin-3-gallate (ECG), (−)-epigallocatechin (EGC) and (−)-epigallocatechin-3-gallate (EGCG), of which the latter is the most active and abundant and matcha is their best condensed source. Due to its unique chemical composition and prized flavour, which sets it apart from other tea beverages, it is considered the highest quality tea. Its health-promoting properties are attributed to the high content of antioxidant and anti-inflammatory substances. Studies confirming the high antioxidant potential of tea beverages claim that it originates from the considerable content of catechins, a type of phenolic compound with beneficial effects on human health. Due to its potential for preventing many diseases and supporting cognitive function, regular consumption of matcha may have a positive effect on both physical and mental health. The aim of this review was to compile the health benefits of matcha tea. It is the first such review to be undertaken, and presents its main bioactive compounds in a systematic manner.

https://www.mdpi.com/1420-3049/26/1/85/pdf

Health Benefits and Chemical Composition of Matcha Green Tea: A Review

Acquired immunodeficiency syndrome (AIDS) complicated with tuberculosis (TB) is a global public issue. Due to the paucity of bacteria in AIDS/TB, blood-based biomarkers that reflect disease severity are desired. Plasma levels of matricellular proteins, such as osteopontin (OPN) and galectin-9 (Gal-9), are known to be elevated in AIDS and TB. Therefore, full-length (FL)-Gal9 and FL-OPN, and their truncated forms (Tr-Gal9, Ud-OPN), and 38 cytokines/chemokines were measured in the plasma of 24 AIDS (other than TB), 49 TB, and 33 AIDS/TB patients. Receiver-operating characteristic analysis was used to screen molecules that could distinguish either between disease and normal group, among each disease group, or between deceased patients and survivors. Selected molecules were further analyzed for significant differences. Tr-Gal9 had the highest ability to differentiate TB from AIDS or AIDS/TB, while Ud-OPN distinguished multidrug resistance (MDR)-TB from non-MDR TB, and extra-pulmonary TB from pulmonary TB. Molecules significantly elevated in deceased patients included; FL-Gal9, Tr-Gal9, interleukin (IL)-1 receptor antagonist, IL-17A and transforming growth factor-α in AIDS; IL-6, granulocyte colony-stimulating factor and monocyte chemotactic protein-1 in TB; and macrophage inflammatory protein-1β in AIDS/TB. From the sensitivity, specificity, and significant elevation, Tr-Gal9 is the best biomarker of inflammation and severity in AIDS and AIDS/TB.

https://www.mdpi.com/2218-273X/10/11/1495/pdf

Plasma Levels of a Cleaved Form of Galectin-9 Are the Most Sensitive Biomarkers of Acquired Immune Deficiency Syndrome and Tuberculosis Coinfection.

The Effect of Tea Catechins on Natural Killer Cell Activity in the Elderly: A Pilot Study

Green tea catechin ingestion or gargling exhibit anti-viral activity against upper respiratory infection. We hypothesized that retention in the oral cavity could improve the anti-viral effects of catechins. The present study investigated the oral retention of catechins in humans and the effect of catechin beverage viscosity on oral retention. Two intervention studies with different test beverages, beverage-C (40 mL, containing 73.4 mg of catechins) and beverage-XT (40 mL, beverage-C containing 100 mg xanthan gum) were conducted in 20 healthy volunteers (mean age 38.7 years). Catechin concentrations were measured in buccal mucosa samples collected at 10 min, 40 min, and 60 min after ingesting test beverages, and the catechin variability of the tissue after intake was compared between test beverages. As a result, the mean (SEM) concentrations of EGCG were 99.9 (27.2), 58.2 (16.6), and 22.3 (5.7) ng/mg-mucosa at 10, 40, and 60 min, respectively, after ingestion of beverage-XT. Similarly, the catechin concentrations were 86.1 (20.3), 32.2 (5.3), and 27.8 (5.9) ng/mg-mucosa after ingestion of beverage-C. The total retention volume over 60 min tended to be slightly higher after ingestion of beverage-XT, though the difference was not statistically significant. Additional studies are needed to confirm the effect of xanthan gum on improving oral retention of catechins.

Investigation of the Oral Retention of Tea Catechins in Humans: An Exploratory Interventional Study.

This retrospective cohort study was performed to investigate the association between risperidone and deteriorating performance in walking and dressing in subjects with Parkinson's disease using the Japanese Diagnosis Procedure Combination data. These data include inpatient claims including information from the time of admission to discharge from 89 acute phase National Hospitals in Japan. The data were evaluated by implementing the inverse probability of treatment weighting, using propensity scores estimated from the clinical characteristics of subjects prescribed risperidone or quetiapine. The generalized estimation equation was used to estimate the adjusted risk ratios (aRRs) and 95% confidence intervals (CIs). In total, 304 subjects were eligible for participation, and were hospitalized between April 2012 and March 2017 (108 and 196 for risperidone and quetiapine groups, respectively). The performance of walking deteriorated at discharge, with 22.2% and 10.2% recorded at admission for the risperidone and quetiapine groups (aRR, 1.7; 95% CI, 0.9 to 3.4), respectively. The performance of dressing also deteriorated: 24.1% and 10.7% in the risperidone and quetiapine groups (aRR, 1.9; 95% CI, 1.04 to 3.7), respectively. These results suggest an association between risperidone and deteriorating performance in dressing in subjects with Parkinson's disease in comparison with quetiapine.

Comparison of the association of risperidone and quetiapine with deteriorating performance in walking and dressing in subjects with Parkinson's disease: a retrospective cohort study using administrative claims data.

Risk stratification for physical morbidity using factors associated with atypical antipsychotic treatment in Parkinson's disease: A retrospective observational study using administrative claims data.

Daisuke Furushima

Papers

Plasma Levels of a Cleaved Form of Galectin-9 Are the Most Sensitive Biomarkers of Acquired Immune Deficiency Syndrome and Tuberculosis Coinfection.

The Effect of Tea Catechins on Natural Killer Cell Activity in the Elderly: A Pilot Study

Investigation of the Oral Retention of Tea Catechins in Humans: An Exploratory Interventional Study.

Comparison of the association of risperidone and quetiapine with deteriorating performance in walking and dressing in subjects with Parkinson's disease: a retrospective cohort study using administrative claims data.

Risk stratification for physical morbidity using factors associated with atypical antipsychotic treatment in Parkinson's disease: A retrospective observational study using administrative claims data.