Monofluorophore-based Two-Photon Ratiometric Fluorescent Probe for the Quantitative Imaging of Fatty Acid Amide Hydrolase in Live Neurons and Mouse Brain Tissues.

Fatty acid amide hydrolase (FAAH) plays a crucial role in the metabolism of the endocannabinoid system by hydrolyzing a series of bioactive amides, whose abnormal levels are associated with neuronal disorders including Alzheimer's disease (AD). However, due to the lack of suitable quantitative sensing tools, real-time and accurate monitoring of the activity of FAAH in living systems remains unresolved. Herein, a novel enzyme-activated near-infrared two-photon ratiometric fluorescent probe (CANP) based on a naphthylvinylpyridine monofluorophore is successfully developed, in which the electron-withdrawing amide moiety is prone to be hydrolyzed to an electron-donating amine group under the catalysis of FAAH, leading to the activation of the intramolecular charge transfer process and the emergence of a new 80 nm red-shifted emission, thereby achieving a ratiometric luminescence response. Benefiting from the high selectivity, high sensitivity, and ratiometric response to FAAH, the probe CANP is successfully used to quantitatively monitor and image the FAAH levels in living neurons, by which an amyloid ß (Aß)-induced upregulation of endogenous FAAH activity is observed. Similar increases in FAAH activity are found in various brain regions of AD model mice, indicating a potential fatty acid amide metabolite-involved pathway for the pathological deterioration of AD. Moreover, our quantitative FAAH inhibition experiments further demonstrate the great value of CANP as an efficient visual probe for in situ and precise assessment of FAAH inhibitors in complex living systems, assisting the discovery of FAAH-related therapeutic agents.

Application effect of gastrointestinal bundle nursing on the protection of gastrointestinal function in patients with gastric cancer.

Evidence-based nursing practice was used to formulate the enhanced recovery surgery bundle nursing strategy and apply it to patients with gastric cancer, to explore its safety, effectiveness and feasibility in perioperative gastrointestinal function protection in patients with gastric cancer. Selected the clinical medical records of 100 gastric cancer patients treated in our hospital from June 2019 to June 2021 as the research objects, and divided them into the control group and the observation group with 50 cases in each group according to the random number table. Among them, the control group was given routine nursing measures for nursing intervention, and the observation group was given gastrointestinal enhanced recovery surgery cluster nursing on the basis of the control group. The differences in stress response, gastrointestinal function protection, negative emotions and pain scores of gastric cancer patients before and after nursing were compared between the 2 groups. The postoperative bowel sounds recovery time, first anal exhaust, and first defecation time in the observation group were lower than those in the control group, and the differences were statistically significant (P < .05). Before nursing, there was no significant difference in the scores of stress response changes between the 2 groups (P > .05). After nursing, heart rate (HR), mean arterial pressure (MAP), norepinephrine (NE), and epinephrine (E2) in the observation group were lower than those in the control group, and the difference was statistically significant (P < .05). The pain scores of the 2 groups were significantly improved at different time points, and the observation group was significantly less than the control group, and the difference was statistically significant (P < .05). Gastrointestinal enhanced recovery surgery bundle nursing can effectively improve the gastrointestinal function of patients with gastric cancer, improve the emotional response and stress response of patients, and has certain reference value for the nursing of patients with gastric cancer.

Fc-competent multispecific PDL-1/TIGIT/LAG-3 antibodies potentiate superior anti-tumor T cell response.

The landscape of current cancer immunotherapy is dominated by antibodies targeting PD-1/PD-L1 and CTLA-4 that have transformed cancer therapy, yet their efficacy is limited by primary and acquired resistance. The blockade of additional immune checkpoints, especially TIGIT and LAG-3, has been extensively explored, but so far only a LAG-3 antibody has been approved for combination with nivolumab to treat unresectable or metastatic melanoma. Here we report the development of a PDL1 × TIGIT bi-specific antibody (bsAb) GB265, a PDL1 × LAG3 bsAb GB266, and a PDL1 × TIGIT × LAG3 tri-specific antibody (tsAb) GB266T, all with intact Fc function. In in vitro cell-based assays, these antibodies promote greater T cell expansion and tumor cell killing than benchmark antibodies and antibody combinations in an Fc-dependent manner, likely by facilitating T cell interactions (bridging) with cancer cells and monocytes, in addition to blocking immune checkpoints. In animal models, GB265 and GB266T antibodies outperformed benchmarks in tumor suppression. This study demonstrates the potential of a new generation of multispecific checkpoint inhibitors to overcome resistance to current monospecific checkpoint antibodies or their combinations for the treatment of human cancers.

Relationship Between Plasma Growth Differentiation Factor 15 Levels and Complications of Type 2 Diabetes Mellitus: A Cross-sectional Study.

OBJECTIVE: Our aim in this study was to identify the associations between growth differentiation factor 15 (GDF15) and type 2 diabetes mellitus (T2DM) complications in a community-based population in China. METHODS: Based on a cross-sectional study registered in the National Basic Public Health Service for disease management of Changshu in China, a total of 1,689 T2DM patients were enrolled and tested further for plasma GDF15 levels. Macrovascular (cardiovascular disease and diabetic foot) and microvascular (diabetic kidney disease [DKD], diabetic retinopathy, and neuropathy) complications were evaluated. Logistic regression models were conducted to identify the associations of GDF15 with the risk of diabetes complications, and linear regression models were used to assess relationships between GDF15 and other clinical features. RESULTS: Overall, 459 of the 1,689 T2DM patients (27.18%) had complications. GDF15 levels were significantly higher in patients with any type of complication compared with their counterparts. With each standard deviation increase of base 10 logarithms of GDF15 (lg-GDF15), the risk of overall complications increased by 1.17-fold (95% confidence interval [CI], 1.03 to 1.32). In contrast to macrovascular complications, associations of GDF15 with microvascular complications appeared to be stronger (adjusted odds ratio [OR], 1.24; 95% CI, 1.08 to 1.43), especially for DKD (adjusted OR, 1.51; 95% CI, 1.19 to 1.93). Subgroup analyses showed that the strength of association between GDF15 and complications varied by distinct age and T2DM duration subgroups. Patients with 2 or more types of complications had higher levels of GDF15 than those with fewer types of complications. Also, linear relationships were identified between GDF15 and several liver and kidney function indices. CONCLUSION: Higher GDF15 levels were associated with T2DM complications, especially DKD. GDF15 may serve as a biomarker for monitoring the deterioration of T2DM.

A novel IgG Fc by computer-aided design enhances heavy-chain heterodimerization in bi- or trispecific antibodies.

The classical `knob-into-holes' (KIH) strategy (knob(T366Y)/hole (Y407T)) has successfully enhanced the heterodimerization of a bispecific antibody (BsAb) resulting in heterodimer formation up to 92% of protein A (ProA)-purified protein pool. However, it does not show high efficiency for every BsAb. KIH was initially applied to a CD20/CD3 BsAb. After in silico modeling, two additional new mutations, S354Y in knob-heavy chain (HC) and Q347E in hole-HC, together with KIH named `ETYY', were introduced in the Fc. The CD20/CD3 BsAb hybrid only represented ~ 50% of the ProA-purified protein pool when KIH was applied. With ETYY, the percentage of CD20/CD3 hybrid increased to 93.8%. CD20/CD3-v4b (containing ETYY) retains the original activity of the BsAb at both Fab and Fc regions, and also shows good developability. These results indicate that the computer-aided novel ETYY design has the potential to improve the development of next-generation BsAbs with higher yields and simpler purification.

Biological activity validation of a computationally designed Rituximab/CD3 T cell engager targeting CD20+ cancers with multiple mechanisms of action.

BACKGROUND: Bispecific T cell engaging antibodies (TEAs) with one arm targeting a cancer antigen and another arm binding to CD3 have demonstrated impressive efficacy in multiple clinical studies. However, establishing a safety/efficacy balance remains challenging. For instance, some TEAs have severe safety issues. Additionally, not all patients or all cancer cells of one patient respond equally to TEAs. METHODS: Here, we developed a next-generation bispecific TEA with better safety/efficacy balance and expanded mechanisms of action. Using the computer-aided antibody design strategy, we replaced heavy chain complementarity-determining regions (HCDRs) in one Rituximab arm with HCDRs from a CD3 antibody and generated a novel CD20/CD3 bispecific antibody. RESULTS: After series of computer-aided sequence optimization, the lead molecule, GB261, showed great safety/efficacy balance both in vitro and in animal studies. GB261 exhibited high affinity to CD20 and ultra-low affinity to CD3. It showed comparable T cell activation and reduced cytokine secretion compared with a benchmark antibody (BM). ADCC and CDC caused by GB261 only killed CD20+ cells but not CD3+ cells. It exhibited better RRCL cell killing than the BM in a PBMC-engrafted, therapeutic treatment mouse model and good safety in cynomolgus monkeys. CONCLUSIONS: Thus, GB261 is a promising novel TEA against CD20+ cancers.

[Effect of triple antibiotic paste on microorganisms in root canals of deciduous teeth].

PURPOSE: To analyze the effect of triple antibiotic paste on root canal microorganisms in periapical periodontitis of different stages. METHODS: Eighty-nine children with periapical periodontitis of deciduous teeth in Department of Stomatology, Children's Hospital of Nanjing Medical University from April 2017 to April 2020 were enrolled, and divided into two groups according to the clinical symptoms and root X-ray films, i.e., acute inflammation group and chronic inflammation group. Samples of infected root canals were collected for bacterial identification, isolation and purification. The detection of microorganisms in the infected root canal and the composition of anaerobic microorganisms were analyzed in both groups. Disk diffusion method was used to observe antimicrobial effects of triple antibiotic paste and calcium hydroxide against common anaerobic bacteria, and the sensitivity of different anaerobic bacteria to triple antibiotic paste. Statistical analysis was completed by SPSS 20.0 software package. RESULTS: The microorganisms in both groups were mainly anaerobic bacteria. The detection rates of aerobes and anaerobic bacteria in the infected root canals had no significant difference between the two groups (P>0.05). The top five anaerobes detected in infected root canals were Peptostreptococcus, Bacteroidetes, Enterococcus faecalis, Porphyromonas gingivalis and Fusobacterium nucleatum. The detection rates of Porphyromonas gingivalis, Fusobacterium nucleatum and Bacteroidetes in infected root canal of acute inflammation group were significantly higher than those of chronic inflammation group, and the detection rate of Enterococcus faecalis was significantly lower than that of chronic inflammation group(P<0.05). The bacteriostatic circle diameter of triple antibiotic paste against Peptostreptococcus, Bacteroidetes, Enterococcus faecalis, Porphyromonas gingivalis and Fusobacterium nucleatum was significantly larger than that of calcium hydroxide(P<0.05). The sensitivity of different anaerobic bacteria to triple antibiotic paste was highest in Enterococcus faecalis, followed by Peptostreptococcus, Porphyromonas gingivalis, Fusobacterium nucleatum, and Bacteroidetes(P<0.05). CONCLUSIONS: Triple antibiotic paste has good antimicrobial effect on the common bacteria in the infected root canal of acute and chronic periapical periodontitis.

Correlation between CYP1A1 polymorphisms and susceptibility to glyphosate-induced reduction of serum cholinesterase: A case-control study of a Chinese population.

Glyphosate (GLP) is one of the most common herbicides worldwide. The serum cholinesterase (ChE) may be affected when exposed to glyphosate. Reduction of serum ChE by herbicides is probably related to cytochrome P450 (CYP450) family polymorphisms. We suspect that the abnormal ChE caused by GLP could be correlated with the CYP family members. To determine whether CYP1B1 (rs1056827 and rs1056836) and CYP1A1 (rs1048943) gene polymorphisms and individual susceptibility to GLP-induced ChE abnormalities were interrelated in the Chinese Han population, we performed this genetic association study on a total of 230 workers previously exposed to GLP, including 115 cases with reduced serum ChE and 115 controls with normal serum ChE. Two even groups of cases and controls were enrolled. The CYP1A1 and CYP1B1 polymorphisms in both groups were genotyped using TaqMan. Subjects with the CYP1A1 rs619586 genotypes showed an increased risk of GLP-induced reduction of serum ChE, which was more evident in the following subgroups: female, > 35 years old, history of GLP exposure time <10 years and >10 years, nonsmoker and nondrinker. The results show that CYP1A1 rs619586 was significantly associated with the GLP-induced reduction in serum ChE and could be a biomarker of susceptibility for Chinese GLP exposed workers. Because of a large number of people exposed to glyphosate, this study has a significance in protecting their health.

[Association of DNMT3a's single nucleotide polymorphisms with susceptibility to noise-induced hearing loss in Chinese workers].

OBJECTIVE: To investigate the potential association of DNMT3a's single nucleotide polymorphism with susceptibility to noise-induced hearing loss( NIHL) in Chinese noise-exposed workers. METHODS: A case-control study was performed, and 998 noise-exposed workers from a chemical fibre factory and an energy company, who underwent occupational health examination in 2015, were enrolled as study subjects. Then, general information and noise exposure of the study subjects were obtained through questionnaire survey and on-site noise detection. According to the result of audiological evaluation, they were divided into case group( n = 498, high-frequency threshold shift >25 dB) and man-matched control group( n = 500, high-frequency threshold shift ≤25 dB). At last, genotyping of DNMT3a rs7590760 was conducted with TaqMan-PCR technique. RESULTS: In the dominant model, the distribution of rs7590760 genotypes between the case group and the control group was statistically significant( P = 0. 001). The NIHL risk of subjects with CC/CG genotype is 1. 56 times the risk of those carrying GG genotype, with an adjusted OR = 1. 56( 95% CI 1. 22-2. 01). After the noise exposure period and noise exposure intensity were stratified, the adjusted OR values for noise exposure period ≤16 years, > 16 years and noise intensity ≤85, 86-92 and >92 dB were respectively 1. 67( 95% CI 1. 17-2. 38), 1. 52( 95% CI 1. 06-2. 17), 1. 56( 95% CI 1. 06-2. 30), 1. 67( 95% CI 0. 94-2. 99) and 1. 51( 95% CI 1. 01-2. 26). CONCLUSION: The CC/CG genotype of rs7590760 in DNMT3a gene is a potential risk factor for noise-induced hearing loss in Chinese noise-exposed workers.

Genetic variation in KCNQ4 gene is associated with susceptibility to noise-induced hearing loss in a Chinese population.

Noise-induced hearing loss (NIHL), one of the most widespread occupational health risks worldwide, is a kind of complex disorder resulting from both genetic and environmental factors. KCNQ4 channels are crucial to the internal ear potassium recycling. To explore whether KCNQ4 polymorphism is associated with individual susceptibility to NIHL, we performed this genetic association study on 571 NIHL cases and 639 normal hearing controls selected from about 2700 Chinese noise-exposed workers. General information and audiometric data were obtained through questionnaires and pure-tone audiometry (PTA). DNA samples were collected and genotyping for three selected SNPs (rs709688, rs2769256 and rs4660468) was performed. Significant differences were observed between cases and controls for the genotype frequency and allele frequency in rs4660468, suggesting that rs4660468 CT/TT genotype and T allele may be risk factors for NIHL. In subjects exposed to noise for more than 16 years (OR = 1.23, 95% CI = 1.09-1.53) and those who exposed to noise >92 dB (OR = 1.29, 95% CI = 1.08-1.69), increased risks of NIHL were found after stratified analysis for rs4660468. Our results suggest that rs4660468 T allele of KCNQ4 involves with a higher risk of NIHL and could be one biomarker of susceptibility for Chinese noise exposed workers.

Effect of simvastatin and microRNA-21 inhibitor on metastasis and progression of human salivary adenoid cystic carcinoma.

Salivary adenoid cystic carcinoma (SACC) is a common malignancy of the salivary glands. Epithelial-mesenchymal transition (EMT) and P53 signaling pathway are associated with SACC metastasis and progression. Although simvastatin (SIM) is effective against the growth of many cancer types, its side effects limit its use. microRNA-21 (miR-21) is highly expressed in a variety of tumors and has a role in promoting tumor development. Therefore, the aim of the present study was to evaluate the effect of SIM in combination with miR-21 inhibitor (miR-21i) against lung metastatic SACC cells (SACC-LM). Our results showed that miR-21i was effective in reducing the resistance of SACC-LM to SIM, resulting in SACC-LM acquisition of epithelial traits, cell migration and invasion reduction, growth inhibition and induction of apoptosis. The expression of proteins associated to metastasis and tumor progression were regulated by the combined use of SIM and miR-21i. Thus, our findings demonstrated that such combination was effective in inhibiting SACC-LM progression, suggesting that multi-target therapy against SACC might represent a potentially successful approach in clinical treatment.

Effect of survivin downregulation by simvastatin on the growth and invasion of salivary adenoid cystic carcinoma.

Simvastatin, an inhibitor of 3­hydroxy­3-methylglutaryl­coenzyme A reductase, is been used in the clinic due to its pleiotropic effects, such as breast cancer, prostate cancer, pancreatic cancer. Simvastatin has recently been demonstrated to serve a potential role in the prophylaxis and therapeutics of a number of human cancers. The majority of reports concerning simvastatin treatment in the majority of human cancers have demonstrated that survivin is significantly decreased as a result and has been implicated in tumorigenesis. However, only a limited number of studies have investigated the use of simvastatin for the treatment of salivary gland adenoid cystic carcinoma (SACC). Therefore, this agent is a candidate for further investigation. The aim of the present study was to investigate the effects of simvastatin on the proliferation, invasion and apoptosis of the human salivary adenoid cystic carcinoma cell line, SACC­83, as well as survivin expression in the cells. The Cell Counting kit­8 assay results revealed that simvastatin inhibited the proliferation of SACC­83 cells in a dose­dependent (10 to 50 µM) and time­dependent (24 to 48 h) manner when compared with the untreated cells. Flow cytometry analysis indicated that simvastatin increased the percentage of cells in early and late apoptosis. Invasion assays revealed that simvastatin treatment inhibited the invasiveness of SACC­83 cells in a dose­dependent manner. In addition, simvastatin downregulated survivin expression in SACC­83 cells. In conclusion, simvastatin significantly inhibited the proliferation and invasion of SACC­83 cells, induced apoptosis, and reduced the expression of survivin, which suggests that simvastatin may be a novel target for SACC therapy.

Role of miR-21 in the growth and metastasis of human salivary adenoid cystic carcinoma.

Aberrant microRNA (miRNA/miR) expression has been reported in various cancer types. miR­21, which is considered to be a proto-oncogene and is frequently overexpressed in certain cancer types, has been implicated in tumorigenesis. The aim of the present study was to investigate the effect of miR­21 degradation on tumor progression and its potential mechanisms in human salivary adenoid cystic carcinoma (SACC) development. Results of reverse transcription­quantitative polymerase chain reaction analysis indicated that SACC cells with high metastatic potential (SACC­LM cells) exhibited a significantly higher expression of miR­21 compared with SACC cells with a lower metastatic potential (SACC­83 cells). In addition, following transfection of SACC­LM cells with miR­21 inhibitor, cell viability was reduced, which may be a result of reduced cell proliferation and metastasis, and the induction of apoptosis, as determined by Cell Counting Kit­8, wound healing, Matrigel invasion and flow cytometry assays. Furthermore, bioinformatics analysis indicated that programmed cell death 4 (PDCD4), phosphatase and tensin homolog deleted on chromosome ten (PTEN) and B­cell lymphoma (Bcl)­2 are potential target genes of miR­21. Therefore, western blotting was performed to investigate the expression of these proteins, and the results demonstrated that miR­21 expression level was negatively associated with PDCD4 and PTEN protein expression, and positively associated with Bcl­2 protein expression, in SACC­LM cells, indicating that miR­21 may promote SACC progression via PDCD4, PTEN and Bcl­2. In conclusion, the present study indicates that miR­21 may be a novel target for SACC therapy and provide a novel basis for the clinical treatment of SACC.

Hearing Loss Characteristics of Workers with Hypertension Exposed to Occupational Noise: A Cross-Sectional Study of 270,033 Participants.

OBJECTIVES: This study investigated the hearing loss characteristics among occupational noise exposure workers with hypertension and the link between hypertension and hearing loss when exposed to occupational noise. METHODS: A total of 267,766 occupational noise-exposed workers were enrolled, including 29,868 workers with hypertension and 240,165 without hypertension. Hypertension was diagnosed according to WHO criteria. Hypertension was classified into four grades based on blood pressure. Assessment of hearing was performed through measurement of an unadulterated tone threshold at different frequencies, which ranged between 250 and 8,000 Hz. RESULTS: A substantial link was observed to exist between hypertension and the increment in the hearing limit. The increase in the hearing threshold was substantially higher among those having grade 2 hypertension. CONCLUSION: The current investigation suggested patients with hypertension exhibit a substantial rise in hearing loss in comparison with patients without hypertension. The rise in hearing loss was significant in patients with grade 2 hypertension. Efficient and practicable measures are required to decrease the hearing loss in workers with hypertension and work-related noise exposure.

Association of genetic variations in FOXO3 gene with susceptibility to noise induced hearing loss in a Chinese population.

Noise induced hearing loss (NIHL), a multifactorial disease involving both genetic and environmental factors, is one of the most important occupational health hazards. Nonetheless, the influence of FOXO3 variants on NIHL risk have not been illuminated. This research was conducted to explore the effects of FOXO3 polymorphisms on individual susceptibility to NIHL. A total of 2689 industrial workers from one textile factory of east China were recruited to participate in the current research. Venous blood was collected, questionnaire and pure-tone audiometry (PTA) was conducted by specialist physicians. Then, we performed genotyping of three selected SNPs (rs2802292, rs10457180, and rs12206094) in FOXO3 gene in 566 NIHL patients and 566 controls. Subsequently, the main effects of genotype and its interactions were evaluated. Our results revealed that individuals with the G allele of rs2802292, G allele of rs10457180, T allele of rs12206094 (OR = 1.43, 1.43, and 1.31 respectively) and the haplotype GAC and others (TGT/GGT/GGC/GAT) (rs2802292-rs10457180-rs12206094) (OR = 1.49 and 2.09 respectively) are associated with an increased risk of NIHL in a Chinese population. Stratified analysis showed that an increased NIHL risk was found in the subjects who exposed to noise >16 years with rs2802292 GG/GT and rs10457180 AG/GG genotype with an OR of 1.62 and 1.66 respectively. Multifactor dimensionality reduction analysis indicated that rs10457180, rs2802292, and rs12206094 have interactions and are related to increased NIHL risk (OR = 1.53). The genetic polymorphism rs2802292, rs10457180, and rs12206094 within FOXO3 gene are associated with an increased risk of NIHL in a Chinese population and have potential to be biomarkers for noise exposed workers.

MiR-92a and miR-486 are potential diagnostic biomarkers for mercury poisoning and jointly sustain NF-κB activity in mercury toxicity.

Occupational and environmental exposure to mercury is a public health concern worldwide. Although the altered epigenetic regulatory features, such as microRNA, have been associated with mercury exposure, the underlying molecular mechanism is not well illuminated. This study aimed to confirm that hsa-miR-92a and hsa-miR-486 are novel diagnostic biomarkers of occupational mercury poisoning, and to explore the underlying mechanism of miR-92a and miR-486 in mercury toxicity. RT-qPCR assays and receiver operating characteristics curve analyses were conducted to confirm the diagnostic value of miR-92a and miR-486 as biomarkers of occupational mercury poisoning. Dual-luciferase assay was applied to confirm the target gene of miR-92a and miR-486 in vitro. Then, we established an in-vitro model where miR-92a and miR-486 were overexpressed or knocked down in HEK-293 and HUVEC cells. RT-qPCR and western blotting were used to analyze gene and protein expression levels. Cell apoptosis was determined by flow cytometry. Results show that miR-92a and miR-486 expression levels were up-regulated in workers exposed to occupational mercury. Upregulation of miR-92a and miR-486 may play a crucial role in mercury toxicity by jointly activating the NF-κB signaling pathway via targeting KLF4 and Cezanne, respectively.

miR-200c regulates endothelin-1 induced PASMCs abnormal proliferation and apoptosis.

miR-200c is an antioncogene in multiple tumors. However, its function in the pathogenesis of pulmonary arterial hypertension (PAH) has not been thoroughly investigated nor understood. In this study, we discovered that miR-200c was able to substantially upregulate in pulmonary arterial smooth muscle cells (PASMCs) treated with endothelin-1 (ET-1). miR-200c also induced cell proliferation and suppressed cell apoptosis in PASMCs in vitro. However, miR-200c had no effect on G1/S/G2 transitions during the cell cycle. Furthermore, we identified miR-200c as a new regulator of the microtubule associated protein 2 (MAP-2) and zinc finger E-box binding homeobox1 (ZEB-1) in PASMCs. miR-200c inhibited MAP-2 and ZEB-1 expression by directly binding to their 3'-untranslated regions(3'UTR) according to luciferase assay results. Our findings provide novel insights into the mechanisms of PAH pathogenesis and potential molecular biomarkers for PAH diagnosis and treatment. © 2017 IUBMB Life, 69(11):877-886, 2017.

Effects of glyphosate exposure on sperm concentration in rodents: A systematic review and meta-analysis.

BACKGROUND: Correlation between exposure to glyphosate and sperm concentrations is important in reproductive toxicity risk assessment for male reproductive functions. Many studies have focused on reproductive toxicity on glyphosate, however, results are still controversial. We conducted a systematic review of epidemiological studies on the association between glyphosate exposure and sperm concentrations of rodents. The aim of this study is to explore the potential adverse effects of glyphosate on reproductive function of male rodents. METHODS: Systematic and comprehensive literature search was performed in MEDLINE, TOXLINE, Embase, WANFANG and CNKI databases with different combinations of glyphosate exposure and sperm concentration. 8 studies were eventually identified and random-effect model was conducted. Heterogeneity among study results was calculated via chi-square tests. Ten independent experimental datasets from these eight studies were acquired to synthesize the random-effect model. RESULTS: A decrease in sperm concentrations was found with mean difference of sperm concentrations(MDsperm)=-2.774×106/sperm/g/testis(95%CI=-0.969 to -4.579) in random-effect model after glyphosate exposure. There was also a significant decrease after fitting the random-effect model: MDsperm=-1.632×106/sperm/g/testis (95%CI=-0.662 to -2.601). CONCLUSIONS: The results of meta-analysis support the hypothesis that glyphosate exposure decreased sperm concentration in rodents. Therefore, we conclude that glyphosate is toxic to male rodent's reproductive system.