Correlation between anti-müllerian hormone in polycystic ovarian syndrome with metformin: a systematic review and meta-analysis.

OBJECTIVE: This study aims to examine the short-term effects of oral metformin (MET) on serum anti-müllerian hormone (AMH) levels and to verify its impact on AMH concentrations in women with polycystic ovary syndrome (PCOS). METHODS: The literature search, extending from January 2000 to April 2023, was conducted using databases such as PubMed, Embase, and the Cochrane Central, resulting in the inclusion of 20 studies. These selected studies, evaluated for quality using the Newcastle-Ottawa Scale, investigated changes in AMH levels before and after treatment, with durations ranging from less than three months to over six months. The reported outcomes were quantified as standardized mean differences (SMD) with 95% confidence intervals (CI). This comprehensive systematic review and meta-analysis was registered with the International Prospective Register of Systematic Reviews (PROSPERO) under the registration number CRD42023420705. The statistical analyses were performed using Review Manager 5.4.1. RESULTS: ① The study incorporated 20 articles, consisting of 12 prospective studies, 7 randomized controlled trials (RCT), and 1 cross-sectional study. ② Serum AMH levels in patients with PCOS diminish subsequent to the oral administration of MET. ③ Across the spectrum of studies analyzed, a pronounced degree of heterogeneity is evident, potentially ascribed to differential parameters including body mass index (BMI), daily pharmacological dosages, the temporal extent of treatment regimens, criteria of PCOS, and detection Methods. ④ The impact of MET on AMH levels exhibits a dose-responsive trend, with escalating doses of MET being associated with progressively greater declines in AMH concentrations in the patient population. ⑤ For women with PCOS receiving MET therapy, a minimum treatment duration of three months may be necessary to observe a reduction in serum AMH levels. CONCLUSIONS: The results of this meta-analysis indicate that MET treatment exerts a suppressive effect on serum AMH levels in women with PCOS. It appears that a treatment duration of at least three months is required to achieve a significant decrease in AMH concentrations. Furthermore, the influence of MET on AMH is dose-dependent, with higher doses correlating with more pronounced reductions in AMH levels among the patients studied.

Help or punishment: acute stress moderates basal testosterone's association with prosocial behavior.

The gonadal hormone testosterone is well-recognized to facilitate various behaviors for obtaining social status. A good reputation (i.e. competitive, generous, and trustworthy) is of crucial importance for acquiring high social status. It is unclear which type of reputation is preferred by individuals under the influence of testosterone. Given that the recent dual-hormone hypothesis emphasizes the modulating effect of stress (cortisol) on the influence of testosterone, it would be intriguing to test the role of stress-induced cortisol in testosterone-related reputation seeking. To test this hypothesis, we induced acute stress in 93 participants with cold pressor test (CPT) paradigm (vs. control condition), and then they were instructed to play a third-party intervention game, in which they made decisions as an uninvolved, outside the third party to punish a violator, help a victim, or do nothing. Salivary samples were obtained to assess participants' testosterone and cortisol levels. We split the testosterone concentration by median to low endogenous testosterone (LT) and high endogenous testosterone (HT). We found that HT individuals' prosocial preferences did not affect by acute stress. They were more likely to choose punishment than helping under both stress and control conditions. In contrast, individuals with low testosterone were more inclined to help than punish under control conditions. Interestingly, acute stress brought behavior patterns of LT individuals closer to those of HT individuals, that is, they reduced their helping behavior and increased the intensity of punishments. In this preliminary study on the preference inducement of testosterone for different types of prosocial behaviors, we discuss the physiological mechanism of the relationship between testosterone and reputation and the implications of these results for the dual-hormone hypothesis.HIGHLIGHTSLow testosterone (LT) individuals were more inclined to help than punish.High testosterone (HT) individuals were more inclined to punish than help.The HT individuals' preferences for prosocial types were not affected by acute stress.Acute stress brought the behavior patterns of LT individuals closer to those of HT individuals.

4D-quantitative proteomics signature of asthenozoospermia and identification of extracellular matrix protein 1 as a novel biomarker for sperm motility.

Asthenozoospermia (AZS), diagnosed by reduced sperm motility, is one of the major causes of male infertility. However, AZS has no effective therapeutic treatment and the underlying molecular mechanism remains largely unclear. In this study, state-of-the-art 4D-quantitative proteomics analysis was used to compare the protein profiling between 7 normozoospermic and 11 asthenozoospermic sperm samples. Overall, 4718 proteins were identified and 1430 differential abundant proteins were found in the two groups. The differentially expressed proteins were analyzed by GO and KEGG. The core deregulated proteins and pathways associated sperm motility dysfunction included energy metabolism and the sperm structure. Integrative analysis further identified extracellular matrix protein 1 (ECM1) as a novel biomarker related to AZS. Our study could provide new insights into the molecular basis of low sperm motility. The mass spectrometric data are available via ProteomeXchange with identifier PXD027637.

Lysates of Lactobacillus acidophilus combined with CTLA-4-blocking antibodies enhance antitumor immunity in a mouse colon cancer model.

Previous reports have suggested that many gut microbiomes were associated with the development of colorectal cancer (CRC), and could modulate response to numerous forms of cancer therapy, including checkpoint blockade immunotherapy. Here we evaluated the protective efficacy of Lactobacillus acidophilus (L. acidophilus) cell lysates combined with an anti-CTL antigen-4 blocking antibody (CTLA-4 mAb) in syngeneic BALB/c mice CRC models induce by a single intraperitoneal injection of 10 mg/kg azoxymethane (AOM), followed by three cycles of 2% dextran sulfate sodium (DSS) in drinking water. In contrast to CTLA-4 mAb monotherapy, L. acidophilus lysates could attenuate the loss of body weight and the combined administration significantly protected mice against CRC development, which suggested that the lysates enhanced antitumor activity of CTLA-4 mAb in model mice. The enhanced efficacy was associated with the increased CD8 + T cell, increased effector memory T cells (CD44 + CD8 + CD62L+), decreased Treg (CD4 + CD25 + Foxp3+) and M2 macrophages (F4/80 + CD206+) in the tumor microenvironment. In addition, our results revealed that L. acidophilus lysates had an immunomodulatory effect through inhibition the M2 polarization and the IL-10 expressed levels of LPS-activated Raw264.7 macrophages. Finally, the 16S rRNA gene sequencing of fecal microbiota demonstrated that the combined administration significantly inhibited the abnormal increase in the relative abundance of proteobacteria and partly counterbalance CRC-induced dysbiosis in model mice. Overall, these data support promising clinical possibilities of L. acidophilus lysates with CTLA-4 mAb in cancer patients and the hypothesis that probiotics help shape the anticancer immune response.

Identification of genes and signaling pathways associated with arthrogryposis­renal dysfunction­cholestasis syndrome using weighted correlation network analysis.

The present study aimed to identify the molecular basis of the arthrogryposis­renal dysfunction­cholestasis (ARC) syndrome, which is caused by mutations in the vacuolar protein sorting 33 homolog B (VPS33B) gene. The microarray dataset GSE83192, which contained six liver tissue samples from VPS33B knockout mice and four liver tissue samples from control mice, was downloaded from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) were screened by the Limma package in R software. The DEGs most relevant to ARC were selected via weighted gene co­expression network analysis to construct a protein­protein interaction (PPI) network. In addition, module analysis was performed for the PPI network using the Molecular Complex Detection function. Functional and pathway enrichment analyses were also performed for DEGs in the PPI network. Potential drugs for ARC treatment were predicted using the Connectivity Map database. In total, 768 upregulated and 379 downregulated DEGs were detected in the VPS33B knockout mice, while three modules were identified from the PPI network constructed. The DEGs in module 1 (CD83, IL1B and TLR2) were mainly involved in the positive regulation of cytokine production and the Toll­like receptor (TLR) signaling pathway. The DEGs in module 2 (COL1A1 and COL1A2) were significantly enriched with respect to cellular component organization, extracellular matrix­receptor interactions and focal adhesion. The DEGs in module 3 (ABCG8 and ABCG3) were clearly associated with sterol absorption and transport. Furthermore, mercaptopurine was identified to be a potential drug (connectivity score=­0.939) for ARC treatment. In conclusion, the results of the current study may help to further understand the pathology of ARC, and the DEGs identified in these modules may serve as therapeutic targets.

A comparative analysis for the development and recovery processes of different types of clogging in lab-scale vertical flow constructed wetlands.

Clogging is a major operational and maintenance issue associated with the use of constructed wetlands. In this study, four lab-scale vertical flow constructed wetlands (VFCW) were used to fully understand the development mechanisms of various types of clogging and their recovery characteristics. The VFCWs were fed with glucose solution, starch suspension with and without bacteriostat, glucose, and starch mixed solution, respectively, to simulate Bio-clogging, organic particle clogging (Op-clogging), inert particle clogging (Ip-clogging), and the combination of Bio-clogging and Op-clogging (C-clogging). Resting operations with water decline were applied to relieve the clogging in the VFCWs. The results indicate that Op-clogging occurred first, followed by C-clogging and Bio-clogging. Ip-clogging took the longest time to develop and did not occur by the end of this study. The microscope analysis found that the extracellular polymeric substances (EPS) bonded the starch particles together to form a dense membrane-like structure and promoted the clogging process. In addition, surface clogging was observed in all four experimental beds. Op-clogging occurred much closer to the surface than those caused by soluble organic matter and inert particles. Furthermore, the growth of biofilm caused significant decline in hydraulic conductivity, whereas its influence on porosity was relatively slight. Moreover, applying resting operation with water decline was effective for recovery from Bio-clogging, Op-clogging, and C-clogging in VFCWs except for Ip-clogging. The results also implied the recovery rates through applying resting operation with water decline were much higher than that with constant water level.

Clogging development and hydraulic performance of the horizontal subsurface flow stormwater constructed wetlands: a laboratory study.

The horizontal subsurface constructed wetland (HSSF CW) is a highly effective technique for stormwater treatment. However, progressive clogging in HSSF CW is a widespread operational problem. The aim of this study was to understand the clogging development of HSSF CWs during stormwater treatment and to assess the influence of microorganisms and vegetation on the clogging. Moreover, the hydraulic performance of HSSF CWs in the process of clogging was evaluated in a tracer experiment. The results show that the HSSF CW can be divided into two sections, section I (circa 0-35 cm) and section II (circa 35-110 cm). The clogging is induced primarily by solid entrapment in section I and development of biofilm and vegetation roots in section II, respectively. The influence of vegetation and microorganisms on the clogging appears to differ in sections I and II. The tracer experiment shows that the hydraulic efficiency (λ) and the mean hydraulic retention time (t mean) increase with the clogging development; although, the short-circuiting region (S) extends slightly. In addition, the presence of vegetation can influence the hydraulic performance of the CWs, and their impact depends on the characteristics of the roots.

Coxsackievirus B3 Induces Autophagic Response in Cardiac Myocytes in vivo.

Viral myocarditis is a common disease that contributes to dilated cardiomyopathy or heart failure. Coxsackievirus B (CVB) is one of the major causative pathogens of viral myocarditis. Previous studies have shown that autophagy is exploited to promote CVB replication in cell lines. To study whether cardiac myocytes respond to CVB infection in a similar way, viral myocarditis was established by the inoculation of 3-week-old BALB/c mice with CVB3. Electron microscopic observation showed that autophagosome-like vesicles were induced in the cardiac myocytes of mice infected by CVB3 at 3, 5, and 7 days after viral infection. The lipidated microtubule-associated protein 1 light chain 3 (LC3), LC3-II, was also significantly increased in both myocardium and the cardiac myocytes extracted from the ventricles of mice infected with CVB3. The increased LC3-II coincided with high level of viral RNA and proteins in both myocardium and isolated cardiac myocytes. Moreover, viral protein synthesis was significantly decreased in primary cardiac myocytes by the treatment with 3-methyladenine, an inhibitor of autophagy. The expression and the phosphorylation of extracellular signal regulated kinase (ERK) were also increased in both myocardium and in the isolated cardiac myocytes of the virus-infected mice, while the interplay of ERK with autophagic response remains to be studied. This study demonstrated that cardiac myocytes respond to CVB3 infection by increased formation of autophagosomes in vivo, which might be exploited for viral replication.

A functional nuclear localization sequence in the VP1 capsid protein of coxsackievirus B3.

The capsid proteins of some RNA viruses can translocate to the nucleus and interfere with cellular phenotypes. In this study we found that the VP1 capsid protein of coxsackievirus B3 (CVB3) was dominantly localized in the nucleus of the cells transfected with VP1-expressing plasmid. The VP1 nuclear localization also occurred in the cells infected with CVB3. Truncation analysis indicated that the VP1 nuclear localization sequence located near the C-terminal. The substitution of His220 with threonine completely abolished its translocation. The VP1 proteins of other CVB types might have the nuclear localization potential because this region was highly conserved. Moreover, the VP1 nuclear localization induced cell cycle deregulation, including a prolonged S phase and shortened G2-M phase. Besides these findings, we also found a domain between Ala72 and Phe106 that caused the VP1 truncates dotted distributed in the cytoplasm. Our results suggest a new pathogenic mechanism of CVB.

Allografts of the acellular sciatic nerve and brain-derived neurotrophic factor repair spinal cord injury in adult rats.

OBJECTIVE: We aimed to investigate whether an innovative growth factor-laden scaffold composed of acellular sciatic nerve (ASN) and brain-derived neurotrophic factor (BDNF) could promote axonal regeneration and functional recovery after spinal cord injury (SCI). METHODS: Following complete transection at the thoracic level (T9), we immediately transplanted the grafts between the stumps of the severed spinal cords. We evaluated the functional recovery of the hindlimbs of the operated rats using the BBB locomotor rating scale system every week. Eight weeks after surgery, axonal regeneration was examined using the fluorogold (FG) retrograde tracing method. Electrophysiological analysis was carried out to evaluate the improvement in the neuronal circuits. Immunohistochemistry was employed to identify local injuries and recovery. RESULTS: The results of the Basso-Beattie-Bresnahan (BBB) scale indicated that there was no significant difference between the individual groups. The FG retrograde tracing and electrophysiological analyses indicated that the transplantation of ASN-BDNF provided a permissive environment to support neuron regeneration. CONCLUSION: The ASN-BDNF transplantation provided a promising therapeutic approach to promote axonal regeneration and recovery after SCI, and can be used as part of a combinatory treatment strategy for SCI management.

[Effect of a novel tyrosine kinase inhibitor HHGV678 on growth inhibition of Bcr-Abl wild type and IM-resistant cell lines in vitro].

This study was aimed to compare HHGV678 with imatinib (IM) in growth inhibition of Bcr-Abl wild type and IM-resistant cell lines, investigate the possibility of replacing IM with HHGV678 in treatment of chronic myeloid leukemia (CML) and IM-resistant CML patients. Viability of two Bcr-Abl wild type cell lines (K562 and 32Dp210) and 16 IM-resistant cell lines (K562R and 15 Bcr-Abl point mutant cell lines) treated with HHGV678 and IM was analyzed by MTT. The apoptosis of those cells was identified by flow cytometry with Annexin V staining and DNA ladder analysis. Western blot was applied for detecting the expression of Bcr-Abl and phosphotyrosine protein levels. The results indicated that HHGV678 significantly inhibited the growth of two Bcr-Abl wild types and IM-resistant cell lines in dose-dependent manner except cell line of T315I point mutant. IC(50) results showed that the growth inhibition of HHGV678 was 15.5 and 28-fold higher than that of IM in K562, 32Dp210 and 1.4 to 124.3-fold higher than that of IM in 15 IM-resistant cell lines respectively. Compared with IM, HHGV678 more significantly inhibited phosphotyrosine kinase protein of the cells mentioned above at different concentrations. With most importance, HHGV678 of 10.0 micromol/L induced cell apoptosis of 40.06% and 33.32% in K562R and 32Dp210(T315I) cell lines, which were much higher than that of IM (19.77% and 10.68%). It is concluded that HHGV678 is more effective than IM in the growth inhibition of Bcr-Abl wild type cell lines and IM-resistant cell lines, especially in strongest IM-resistant cell lines. Further studies are needed to show whether HHGV678 may be a novel targeting drug in treatment of CML and IM-resistant CML patients.