Given that the PI3K/AKT pathway has manifested its compelling influence on multiple cellular process, we further review the roles of hyperactivation of PI3K/AKT pathway in various human cancers. We state the abnormalities of PI3K/AKT pathway in different cancers, which are closely related with tumorigenesis, proliferation, growth, apoptosis, invasion, metastasis, epithelial-mesenchymal transition, stem-like phenotype, immune microenvironment and drug resistance of cancer cells. In addition, we investigated the current clinical trials of inhibitors against PI3K/AKT pathway in cancers and found that the clinical efficacy of these inhibitors as monotherapy has so far been limited despite of the promising preclinical activity, which means combinations of targeted therapy may achieve better efficacies in cancers. In short, we hope to feature PI3K/AKT pathway in cancers to the clinic and bring the new promising to patients for targeted therapies.

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Role of PI3K/AKT pathway in cancer: the framework of malignant behavior.

Summary Background Previous studies on the pneumonia outbreak caused by the 2019 novel coronavirus disease (COVID-19) were based on information from the general population. Limited data are available for pregnant women with COVID-19 pneumonia. This study aimed to evaluate the clinical characteristics of COVID-19 in pregnancy and the intrauterine vertical transmission potential of COVID-19 infection. Methods Clinical records, laboratory results, and chest CT scans were retrospectively reviewed for nine pregnant women with laboratory-confirmed COVID-19 pneumonia (ie, with maternal throat swab samples that were positive for severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) who were admitted to Zhongnan Hospital of Wuhan University, Wuhan, China, from Jan 20 to Jan 31, 2020. Evidence of intrauterine vertical transmission was assessed by testing for the presence of SARS-CoV-2 in amniotic fluid, cord blood, and neonatal throat swab samples. Breastmilk samples were also collected and tested from patients after the first lactation. Findings All nine patients had a caesarean section in their third trimester. Seven patients presented with a fever. Other symptoms, including cough (in four of nine patients), myalgia (in three), sore throat (in two), and malaise (in two), were also observed. Fetal distress was monitored in two cases. Five of nine patients had lymphopenia ( Interpretation The clinical characteristics of COVID-19 pneumonia in pregnant women were similar to those reported for non-pregnant adult patients who developed COVID-19 pneumonia. Findings from this small group of cases suggest that there is currently no evidence for intrauterine infection caused by vertical transmission in women who develop COVID-19 pneumonia in late pregnancy. Funding Hubei Science and Technology Plan, Wuhan University Medical Development Plan.

Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records

INTRODUCTION
The role of testosterone supplementation (TS) as a treatment for male sexual dysfunction remains questionable.


AIM
The aim of this study was to attempt a meta-analysis on the effect of TS on male sexual function and its synergism with the use of phosphodiesterase type 5 inhibitor (PDE5i).


METHODS
An extensive Medline, Embase, and Cochrane search was performed.


MAIN OUTCOME MEASURES
All randomized controlled trials (RCTs) comparing the effect of TS vs. placebo or the effect of TS as add on to PDE5is on sexual function were included. Data extraction was performed independently by two of the authors (A. M. Isidori and G. Corona), and conflicts resolved by the third investigator (M. Maggi).


RESULTS
Out of 1,702 retrieved articles, 41 were included in the study. In particular, 29 compared TS vs. placebo, whereas 12 trials evaluated the effect of TS as add on to PDE5is. TS is able to significantly ameliorate erectile function and to improve other aspects of male sexual response in hypogonadal patients. However, the presence of possible publication bias was detected. After applying "trim and fill" method, the positive effect of TS on erectile function and libido components retained significance only in RCTs partially or completely supported by pharmaceutical companies (confidence interval [0.04-0.53] and [0.12; 0.52], respectively). In addition, we also report that TS could be associated with an improvement in PDE5i outcome. These results were not confirmed in placebo-controlled studies. The majority of studies, however, included mixed eugonadal/hypogonadal subjects, thus imparting uncertainty to the statistical analyses.


CONCLUSIONS
TS plays positive effects on male sexual function in hypogonadal subjects. The role of TS is uncertain in men who are not clearly hypogonadal. The apparent difference between industry-supported and independent studies could depend on trial design more than on publication bias. New RCTs exploring the effect of TS in selected cases of PDE5i failure that persistently retain low testosterone levels are advisable.

Testosterone supplementation and sexual function: a metaanalysis study

1822 Recent reports show that AR is the key determinant for the molecular changes required for resistance to apoptosis and for driving prostate cancer cells from an androgen-dependent to androgen depletion, independent (ADI) state. Further recent publications suggest that downregulation of AR expression should therefore be considered the main strategy for the treatment of ADI disease. However, there is little data about how androgen-dependent cancer cells respond to apoptosis-inducing agents after knocking down AR expression. We therefore investigated whether downregulation of AR expression using siRNA AR (si-AR) would be effective for inducing apoptosis in combination with apoptosis-inducing agents. si-AR prevented apoptosis induced by the DNA damage inducing drugs doxorubicin (DOX) and camptothecin (Campt). These agents activate, i.e. phosphorylate, p53, which in turn regulates the expression of a variety of apoptosis-related genes, including microRNA-34a and 34b/c. We investigated 7 phosphorylation sites of p53 after DOX treatment and found that DOX induced 5 of them (Ser15, 20, 37, 46, and 392); phosphorylation of all 5 sites was inhibited by si-AR. This suggests that at least two kinases are involved in AR-mediated suppression of p53. We have also found that three kinases (SPAK, NFBD1, and CaMKII) are under AR control and participate in events upstream of p53 that result in p53 inhibition. Using q PCR we then investigated miRNA-34a and -34c expression. The level of miRNA-34a increased 3X after DOX treatment but no increase was found in si-AR cells; the level of miRNA-34c increased 27X after DOX and only by 2X with si-AR. The data suggest that AR-dependent inhibition of p53 results in suppression of microRNA-34a and -34c that in turn inhibits DOX-induced apoptosis. To directly investigate the role of microRNA-34 in apoptosis, we transfected cells with anti-microRNA-34 oligonucleotides or with microRNA-34, and found that anti-microRNA-34a/c inhibited DOX-mediated apoptosis whereas microRNA-34a/c enhanced DOX-mediated apoptosis; even without DOX treatment microRNA-34 transfection itself induced caspase activity. Taken together, our data indicate that microRNA-34a and 34c play important roles in AR-dependent p53-mediated apoptosis in prostate cancer.

MicroRNA-34 mediates AR-dependent p53-induced apoptosis in prostate cancer

To date, seven identified coronaviruses (CoVs) have been found to infect humans; of these, three highly pathogenic variants have emerged in the 21st century. The newest member of this group, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first detected at the end of 2019 in Hubei province, China. Since then, this novel coronavirus has spread worldwide, causing a pandemic; the respiratory disease caused by the virus is called coronavirus disease 2019 (COVID-19). The clinical presentation ranges from asymptomatic to mild respiratory tract infections and influenza-like illness to severe disease with accompanying lung injury, multiorgan failure, and death. Although the lungs are believed to be the site at which SARS-CoV-2 replicates, infected patients often report other symptoms, suggesting the involvement of the gastrointestinal tract, heart, cardiovascular system, kidneys, and other organs; therefore, the following question arises: is COVID-19 a respiratory or systemic disease? This review aims to summarize existing data on the replication of SARS-CoV-2 in different tissues in both patients and ex vivo models.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): a Systemic Infection.

Background Since SARS-CoV-2 infection was first identified in December 2019, the novel coronavirus-induced pneumonia COVID-19 spread rapidly and triggered a global pandemic Recent bioinformatics evidence suggested that angiotensin-converting enzyme 2-the main cell entry target of SARS-CoV-2-was predominantly enriched in spermatogonia, Leydig and Sertoli cells, which suggests the potential vulnerability of the male reproductive system to SARS-CoV-2 infection Objectives To identify SARS-CoV-2 RNA in seminal plasma and to determine semen characteristics from male patients in the acute and recovery phases of infection Methods From February 26 to April 2, 2020, 23 male patients with COVID-19 were recruited The clinical characteristics, laboratory findings and chest computed tomography scans of all patients were recorded in detail We also investigated semen characteristics and the viral RNA load in semen from these patients in the acute and recovery phases of SARS-CoV-2 infection using approved methods Results The age range of the 23 patients was 20-62 years All patients tested negative for SARS-CoV-2 RNA in semen specimens Among them, the virus had been cleared in 11 patients, as they tested negative The remaining 12 patients tested negative for SARS-CoV-2 RNA in semen samples, but were positive in sputum and fecal specimens The median interval from diagnosis to providing semen samples was 32 days, when total sperm counts, total motile sperm counts, and sperm morphology of the patients were within normal ranges Discussion and conclusion In this cohort of patients with a recent infection or recovering from COVID-19, there was no SARS-CoV-2 RNA detected in semen samples, which indicates the unlikely possibility of sexual transmission through semen at about 1 month after first detection

https://onlinelibrary.wiley.com/doi/pdf/10.1111/andr.12848

Absence of SARS-CoV-2 in semen of a COVID-19 patient cohort.

Prostate cancer (PCa) is the second most frequently diagnosed male cancer, and no treatments exist for effective inhibition of metastatic spread of PCa. Long non-coding RNA (lncRNA) plays key roles in pathogenesis and development of various cancers through competing with endogenous RNAs (ceRNAs), but at present research on lncRNA functions in PCa is still very limited. Hence, this aspect was investigated using bioinformatics methods. Firstly, the functional lncRNA-mediated ceRNA network associated with PCa was constructed by the multi-step computational approach. Then the cytoscape software was used to analyze the node degree and betweenness centrality (BC) value of lncRNAs and mRNAs in the interaction. Finally, the lncRNAs were screened in the central region of the network by the node degree and BC value, and the functional enrichment of mRNAs was evaluated with the Gene Ontology (GO) database. In our results, LINC00476, MALAT1, SNHG11, LINC00649, and ILF3-AS1 are the lncRNAs which have the most nodes and higher BC values and considered as prognostic markers in PCa. GO analysis suggested that the function of screened lncRNAs was obviously focused on intracellular receptor signaling pathway, which indicated these lncRNAs might be potential biomarkers for diagnosis, evaluation and gene-targeted therapy of PCa.

/pdf/identification-of-prognostic-biomarkers-of-prostate-cancer-4shd8q31hf.pdf

Identification of prognostic biomarkers of prostate cancer with long non-coding RNA-mediated competitive endogenous RNA network

Erectile dysfunction (ED) is a common complication of pelvic fractures. To identify the vascular and neurogenic factors associated with ED, 120 patients admitted with ED after traumatic pelvic fracture between January 2009 and June 2013 were enrolled in this study. All patients answered the International Index of Erectile Function (IIEF-5) questionnaire. Nocturnal penile tumescence (NPT) testing confirmed the occurrence of ED in 96 (80%) patients on whom penile duplex ultrasound and neurophysiological testing were further performed. Of these ED patients 29 (30%) were demonstrated only with vascular abnormality, 41 (42.7%) were detected only with neural abnormality, 26 (27.1%) revealed mixed abnormalities. Of the 55 patients (29+26) with vascular problems, 7 patients (12.7%) with abnormal arterial response to intracavernous injection of Bimix (15mg papaverine and 1mg phentolamine), 31 (56.4%) with corporal veno-occlusive dysfunction and 17 (30.9%) had both problems. Of the 67 (41+26) patients with abnormal neurophysiological outcomes, 51 (76.1%) with abnormal bulbocavernosus re?ex (BCR), 20 (29.9%) with pathological pudendal nerve evoked potentials (PDEPs) and 25 (37.3%) with abnormal posterior tibial somatosensory nerve evoked potentials (PTSSEPs). Our observation indicated that neurogenic factors are important for the generation of ED in patients with pelvic fracture; venous impotence is more common than arteriogenic ED.

/pdf/the-vascular-and-neurogenic-factors-associated-with-erectile-p6tnk13gkq.pdf

The vascular and neurogenic factors associated with erectile dysfunction in patients after pelvic fractures

General control non-derepressible 5 (GCN5) is ectopically expressed in different types of human cancer and association with the carcinogenesis, development, and poor prognosis of cancers. The present study was aimed to investigate the potential role and related mechanisms of GCN5 in IL-6–treated prostate cancer (PCa) cell. The results showed that an elevated GCN5 expression was stimulated by IL-6. Knockdown of GCN5 significantly inhibited IL-6–driven proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT). Moreover, early growth response-1 (Egr-1) expression was elevated by IL-6 treatment and GCN5 siRNA down-regulated the expression of Egr-1. Furthermore, overexpression of Egr-1 attenuated the effects of GCN5 silence on cell proliferation, migration, invasion, and EMT in PCa. Besides, knockdown of GCN5 resulted in the down-regulation of p-Akt and up-regulation of PTEN, which was partly impeded by Egr-1 overexpression. The effects of GCN5 overexpression on cell proliferation and invasion were suppressed by LY294002, In conclusion, these data demonstrated the negative effect of up-regulated GCN5 in IL-6-induced metastasis and EMT in PCa cells through PI3K/PTEN/Akt signaling pathway down-regulating Egr-1 expression.

/pdf/gcn5-inhibition-prevents-il-6-induced-prostate-cancer-1dhbhww790.pdf

Mingzhen Yuan

Papers

Absence of SARS-CoV-2 in semen of a COVID-19 patient cohort.

Identification of prognostic biomarkers of prostate cancer with long non-coding RNA-mediated competitive endogenous RNA network

The vascular and neurogenic factors associated with erectile dysfunction in patients after pelvic fractures

GCN5 inhibition prevents IL-6-induced prostate cancer metastases through PI3K/PTEN/Akt signaling by inactivating Egr-1.

Outcomes of Microscopic Subinguinal Varicocelectomy With and Without the Assistance of Doppler Ultrasound: A Randomized Clinical Trial.