Direct trafficking pathways from the Golgi apparatus to the plasma membrane.

In eukaryotic cells, protein sorting is a highly regulated mechanism important for many physiological events. After synthesis in the endoplasmic reticulum and trafficking to the Golgi apparatus, proteins sort to many different cellular destinations including the endolysosomal system and the extracellular space. Secreted proteins need to be delivered directly to the cell surface. Sorting of secreted proteins from the Golgi apparatus has been a topic of interest for over thirty years, yet there is still no clear understanding of the machinery that forms the post-Golgi carriers. Most evidence points to these post-Golgi carriers being tubular pleomorphic structures that bud from the trans-face of the Golgi. In this review, we present the background studies and highlight the key components of this pathway, we then discuss the machinery implicated in the formation of these carriers, their translocation across the cytosol, and their fusion at the plasma membrane.

Accumulation of 3-aminopropylphosphonate in the ex vivo brain observed by phosphorus-31 nuclear magnetic resonance.

3-aminopropylphosphonate (3-APP) is known for its use as an exogenous indicator of extracellular volume and pH in phosphorus-31 nuclear magnetic resonance (31 P NMR) studies. We used 3-APP for estimating the extracellular volume in NMR studies of several ex vivo preparations including retrograde perfused mouse heart (n = 4), mouse liver slices (n = 2), xenograft breast cancer tumors (n = 7, MCF7), and rat brain slices (n = 4). In the former three preparations, the 3-APP signal was stable in lineshape and intensity for hours and the chemical shift of the signal in the presence of the biological sample was the same as in the perfusion medium without the biological sample. However, in studies of brain slices, the 3-APP signal appeared split into two, with an upfield component (0.7 ± 0.1 ppm to the left) increasing with time and showing a wider linewidth (66.7 ± 12.6 vs. 39.1 ± 7.6 Hz, the latter is of the perfusion medium signal). This finding suggests that 3-APP inadvertently accumulated in brain slices, most likely as a membrane bound form. This observation limits the use of 3-APP as an inert biochemical indicator in brain preparations and should be taken into account when using 3-APP in vivo.

Cardioprotective effects of sinomenine in myocardial ischemia/reperfusion injury in a rat model.

Background: Ischemia reperfusion (I/R) play an imperative role in the expansion of cardiovascular disease. Sinomenine (SM) has been exhibited to possess antioxidant, anticancer, anti-inflammatory, antiviral and anticarcinogenic properties. The aim of the study was scrutinized the cardioprotective effect of SM against I/R injury in rat. Methods: Rat were randomly divided into normal control (NC), I/R control and I/R + SM (5, 10 and 20 mg/kg), respectively. Ventricular arrhythmias, body weight and heart weight were estimated. Antioxidant, inflammatory cytokines, inflammatory mediators and plasmin system indicator were accessed. Results: Pre-treated SM group rats exhibited the reduction in the duration and incidence of ventricular fibrillation, ventricular ectopic beat (VEB) and ventricular tachycardia along with suppression of arrhythmia score during the ischemia (30 and 120 min). SM treated rats significantly (P < 0.001) altered the level of antioxidant parameters. SM treatment significantly (P < 0.001) repressed the level of creatine kinase MB (CK-MB), creatine kinase (CK) and troponin I (Tnl). SM treated rats significantly (P < 0.001) repressed the tissue factor (TF), thromboxane B2 (TXB2), plasminogen activator inhibitor 1 (PAI-1) and plasma fibrinogen (Fbg) and inflammatory cytokines and inflammatory mediators. Conclusion: Our result clearly indicated that SM plays anti-arrhythmia effect in I/R injury in the rats via alteration of oxidative stress and inflammatory reaction.

Magnetic particles for integrated nucleic acid purification, amplification and detection without pipetting.

Nucleic acid amplification based detection plays an important role in food safety, environmental monitoring and clinical diagnosis. However, traditional nucleic acid detection process involves transferring liquid from one tube to another by pipetting. It requires trained persons, equipped labs and consumes lots of time. The ideal nucleic acid detection is integrated, closed, simplified and automated. Magnetic particles actuated by magnetic fields can efficiently adsorb nucleic acids and promote integrated nucleic acid assays without pipetting driven by pumps and centrifuges. We will comprehensively review magnetic particles assisted integrated system for nucleic acid detection and hope it can inspire further related study.

Non-pharmacological Interventions for Intractable Epilepsy.

In 30% of epileptic individuals, intractable epilepsy represents a problem for the management of seizures and severely affects the patient's quality of life due to pharmacoresistance with commonly used antiseizure drugs (ASDs). Surgery is not the best option for all resistant patients due to its post-surgical consequences. Therefore, several alternative or complementary therapies have scientifically proven significant therapeutic potential for the management of seizures in intractable epilepsy patients with seizure-free occurrences. Various non-pharmacological interventions include metabolic therapy, brain stimulation therapy, and complementary therapy. Metabolic therapy works out by altering the energy metabolites and include the ketogenic diets (KD) (that is restricted in carbohydrates and mimics the metabolic state of the body as produced during fasting and exerts its antiepileptic effect) and anaplerotic diet (which revives the level of TCA cycle intermediates and this is responsible for its effect). Neuromodulation therapy includes vagus nerve stimulation (VNS), responsive neurostimulation therapy (RNS) and transcranial magnetic stimulation therapy (TMS). Complementary therapies such as biofeedback and music therapy have demonstrated promising results in pharmacoresistant epilepsies. The current emphasis of the review article is to explore the different integrated mechanisms of various treatments for adequate seizure control, and their limitations, and supportive pieces of evidence that show the efficacy and tolerability of these non-pharmacological options.

Physiological Functions of Glial Cell Hemichannels.

The brain performs exceptionally complex and dynamic tasks that depend on the coordinated interaction of neurons, glial cells, endothelial cells, pericytes, smooth muscle cells, ependymal cells, and circulating blood cells. Among these cells, glial cells have emerged as crucial protagonists in the regulation of synaptic transmission and neural function. Indeed, these cells express a wide range of receptors that enable them to sense changes in neuronal activity and the microenvironment by responding locally via the release of bioactive molecules known as gliotransmitters. In the central nervous system (CNS), a novel mechanism that allows gliotransmission via the opening of hemichannels has been proposed. These channels are composed of six protein subunits consisting of connexins or pannexins, which are two highly conserved protein families that are encoded by 21 and 3 genes, respectively, in humans. Typically, glial cell hemichannels exhibit low levels of activity, but this activity is sufficient to ensure the release of a broad spectrum of gliotransmitters, including ATP, D-serine, glutamate, adenosine, and glutathione. Here, we briefly review the current findings regarding the effects of the hemichannel-dependent release of gliotransmitters on the physiology of the CNS.

Corrigendum: 1270 nm near-infrared light as a novel vaccine adjuvant acts on mitochondrial photoreception in intradermal vaccines.

[This corrects the article DOI: 10.3389/fimmu.2022.1028733.].

Human papillomavirus expression in relation to biological behavior, Ki-67 proliferative marker, and P53 prognostic marker in Schneiderian papilloma.

Various malignant and benign tumors can arise in the sinonasal cavity, including inverted papilloma (IP), a benign neoplasm with unique clinical characteristics. However, the mechanisms involved in the recurrence, occurrence, and malignant transformation of IP remain debatable. This study aimed to investigate the impact of human papillomavirus (HPV) infections on IP by comparing the number of infections in cases with epithelial tissue dysplasia and explore the predictive role of proliferative and prognostic markers in dysplasia. Tissue blocks from 35 cases of sinonasal papilloma, collected between 2015 and 2021 from the laboratory archives of the Medical City of Ghazi Al-Hererri Hospital in Baghdad, Iraq, were immunohistochemically stained with monoclonal antibodies (mAbs) to detect Ki-67 and p53. A quantitative immunohistochemical analysis was conducted to analyze the results. Polymerase chain reaction (PCR) was performed to detect HPV genotypes 16/18 and 6/11 in the tissues. There was an insignificant increase in Ki-67 and p53 expression in inverted papillomas with dysplasia. HPV11 was the most prevalent genotype in 34.3% of the patients, followed by HPV16 and HPV18 in 31.4% of the patients for each virus. The least common virus detected was human papillomavirus 6 (8.6%), which did not show any significant association with the degree of dysplasia. Viral detection proliferation and apoptosis had no impact on tumor dysplasia amongst all the patients, showing no relationship with the evaluated cases.

Adipocytes in obesity: A perfect reservoir for SARS-CoV-2?

Research evidence suggests that adipocytes in obesity might facilitate SARS-CoV-2 replication, for it was only found in adipose tissue of individuals with overweight or obesity but not lean individuals who died from COVID-19. As lipid metabolism is key to adipocyte function, and viruses are capable of exploiting and manipulating lipid metabolism of host cells for their own benefit of infection, we hypothesize that adipocytes could not only impair host immune defense against viral infection, but also facilitate SARS-CoV-2 entry, replication and assembly as a reservoir to boost the viral infection in obesity. The latter of which could mainly be mediated by SARS-CoV-2 hijacking the abnormal lipid metabolism in the adipocytes. If these were to be confirmed, an approach to combat COVID-19 in people with obesity by taking advantage of the abnormal lipid metabolism in adipocytes might be considered, as well as modifying lipid metabolism of other host cells as a potential adjunctive treatment for COVID-19.

Hybrid computational models of multicellular tumour growth considering glucose metabolism.

Cancer cells metabolize glucose through metabolic pathways that differ from those used by healthy and differentiated cells. In particular, tumours have been shown to consume more glucose than their healthy counterparts and to use anaerobic metabolic pathways, even under aerobic conditions. Nevertheless, scientists have still not been able to explain why cancer cells evolved to present an altered metabolism and what evolutionary advantage this might provide them. Experimental and computational models have been increasingly used in recent years to understand some of these biological questions. Multicellular tumour spheroids are effective experimental models as they replicate the initial stages of avascular solid tumour growth. Furthermore, these experiments generate data which can be used to calibrate and validate computational studies that aim to simulate tumour growth. Hybrid models are of particular relevance in this field of research because they model cells as individual agents while also incorporating continuum representations of the substances present in the surrounding microenvironment that may participate in intracellular metabolic networks as concentration or density distributions. Henceforth, in this review, we explore the potential of computational modelling to reveal the role of metabolic reprogramming in tumour growth.

Focal segmental glomerulosclerosis with a mutation in the mitochondrially encoded NADH dehydrogenase 5 gene: A case report.

NADH dehydrogenase 5 (ND5) is one of 44 subunits composed of Complex I in mitochondrial respiratory chain. Therefore, a mitochondrially encoded ND5 (MT-ND5) gene mutation causes mitochondrial oxidative phosphorylation (OXPHOS) disorder, resulting in the development of mitochondrial diseases. Focal segmental glomerulosclerosis (FSGS) which had podocytes filled with abnormal mitochondria is induced by mitochondrial diseases. An MT-ND5 mutation also causes FSGS. We herein report a Japanese woman who was found to have proteinuria and renal dysfunction in an annual health check-up at 29 years old. Because her proteinuria and renal dysfunction were persistent, she had a kidney biopsy at 33 years of age. The renal histology showed FSGS with podocytes filled with abnormal mitochondria. The podocytes also had foot process effacement and cytoplasmic vacuolization. In addition, the renal pathological findings showed granular swollen epithelial cells (GSECs) in tubular cells, age-inappropriately disarranged and irregularly sized vascular smooth muscle cells (AiDIVs), and red-coloured podocytes (ReCPos) by acidic dye. A genetic analysis using peripheral mononuclear blood cells and urine sediment cells detected the m.13513 G > A variant in the MT-ND5 gene. Therefore, this patient was diagnosed with FSGS due to an MT-ND5 gene mutation. Although this is not the first case report to show that an MT-ND5 gene mutation causes FSGS, this is the first to demonstrate podocyte injuries accompanied with accumulation of abnormal mitochondria in the cytoplasm.

Expression, regulating mechanism and therapeutic target of KIF20A in multiple cancer.

Kinesin family member 20A (KIF20A) is a member of the kinesin family. It transports chromosomes during mitosis, plays a key role in cell division. Recently, studies proved that KIF20A was highly expressed in cancer. High expression of KIF20A was correlated with poor overall survival (OS). In this review, we summarized all the cancer that highly expressed KIF20A, described the role of KIF20A in cancer. We also organized phase I and phase II clinical trials of KIF20A peptides vaccine. All results indicated that KIF20A was a promising therapeutic target for multiple cancer.

Identifying Novel Genes and Variants in Immune and Coagulation Pathways Associated with Macular Degeneration.

Purpose: To select individuals and families with a low genetic burden for age-related macular degeneration (AMD), to inform the clinical diagnosis of macular disorders, and to find novel genetic variants associated with maculopathies. Design: Genetic association study based on targeted and whole-exome sequencing. Participants: A total of 758 subjects (481 individuals with maculopathy and 277 controls), including 316 individuals in 72 families. Methods: We focused on 150 genes involved in the complement, coagulation, and inflammatory pathways. Single-variant tests were performed on 7755 variants shared among ≥ 5 subjects using logistic regression. Gene-based tests were used to evaluate aggregate effects from rare and low-frequency variants (at minor allele frequency [MAF] ≤ 5% or ≤ 1%) in a gene using burden tests. For families whose affected members had a low burden of genetic risk based on known common and rare variants related to AMD, we searched for rare variants (MAF < 0.001) whose risk alleles occurred in ≥ 80% of affected individuals but not in controls. Immunohistochemistry was performed to determine the protein expression of a novel gene (coagulation factor II thrombin receptor-like 2 [F2RL2]) in retinal tissues. Main Outcome Measures: Genotypes and phenotypes of macular degeneration. Results: We confirmed the association of a synonymous variant in complement factor H (Ala473, rs2274700, proxy to intronic rs1410996, r 2  = 1) with maculopathy (odds ratio, 0.64; P = 4.5 × 10-4). Higher AMD polygenic risk scores (PRSs) were associated with intermediate and advanced AMD. Among families with low PRSs and no known rare variants for maculopathy, we identified 2 novel, highly penetrant missense rare variants in ADAM15, A disintegrin and metalloprotease, metallopeptidase domain 15 (p.Arg288Cys) and F2RL2 (p.Leu289Arg). Immunohistochemistry analyses revealed F2RL2 protein expression in cone photoreceptor outer segments and Müller glia cells of human and pig retinas. Coagulation factor II thrombin receptor-like 2 expression appeared increased in fibrotic areas in advanced AMD samples with neovascularization, suggesting that F2RL2 may play a role in the progression to advanced macular disease. Conclusions: New missense rare variants in the genes ADAM15 and F2RL2 were associated with maculopathies. Results suggest that novel genes related to the coagulation and immune pathways may be involved in the pathogenesis of macular diseases.

Dietary fat types consumption association with obesity and coronary indices.

This article aims to study the different dietary fat types associated with obesity and coronary indices. A sample of 491 healthy adults was included in a cross-sectional manner. Dietary fats intake, obesity indices (conicity index (CI), body adiposity index (BAI), abdominal volume index (AVI), body roundness index (BRI), and weight-adjusted-waist index (WWI)), and cardiovascular indices (cardiometabolic index (CMI), lipid accumulation product (LAP), and atherogenic index of plasma (AIP)) were calculated and studied. Participants with an acceptable intake of omega-3 had a higher BRI score (1⋅90 ± 0⋅06 v. 1⋅70 ± 0⋅06). Participants with an unacceptable intake of cholesterol had a higher CI (1⋅31 ± 0⋅11 v. 1⋅28 ± 0⋅12; P = 0⋅011), AVI (20⋅24 ± 5⋅8 v. 18⋅33 ± 6⋅0; P < 0⋅001), BRI (2⋅00 ± 1⋅01 v. 1⋅70 ± 1⋅00; P = 0⋅003), WWI (11⋅00 ± 0⋅91 v. 10⋅80 ± 0⋅97; P = 0⋅032), and lower AIP (0⋅46 ± 0⋅33 v. 0⋅53 ± 0⋅33; P = 0⋅024). Total fat, saturated fat (SFA), and polyunsaturated fat (PUFA) intake had a significant moderate correlation with AVI and BRI. The monounsaturated fat (MUFA) intake had a significantly weak correlation with CI, AVI, BRI, WWI, and AIP. Cholesterol and omega-6 had weak correlations with all indices. Similar correlations were seen among male and female participants. The different types of fat intake significantly affected obesity and coronary indices, especially SFA and PUFA, as well as omega-3 and cholesterol. Gender and the dietary type of fat intake have a relationship to influence the indicators of both obesity and coronary indices.

Computational tools for exploring peptide-membrane interactions in gram-positive bacteria.

The vital cellular functions in Gram-positive bacteria are controlled by signaling molecules known as quorum sensing peptides (QSPs), considered promising therapeutic interventions for bacterial infections. In the bacterial system QSPs bind to membrane-coupled receptors, which then auto-phosphorylate and activate intracellular response regulators. These response regulators induce target gene expression in bacteria. One of the most reliable trends in drug discovery research for virulence-associated molecular targets is the use of peptide drugs or new functionalities. In this perspective, computational methods act as auxiliary aids for biologists, where methodologies based on machine learning and in silico analysis are developed as suitable tools for target peptide identification. Therefore, the development of quick and reliable computational resources to identify or predict these QSPs along with their receptors and inhibitors is receiving considerable attention. The databases such as Quorumpeps and Quorum Sensing of Human Gut Microbes (QSHGM) provide a detailed overview of the structures and functions of QSPs. The tools and algorithms such as QSPpred, QSPred-FL, iQSP, EnsembleQS and PEPred-Suite have been used for the generic prediction of QSPs and feature representation. The availability of compiled key resources for utilizing peptide features based on amino acid composition, positional preferences, and motifs as well as structural and physicochemical properties, including biofilm inhibitory peptides, can aid in elucidating the QSP and membrane receptor interactions in infectious Gram-positive pathogens. Herein, we present a comprehensive survey of diverse computational approaches that are suitable for detecting QSPs and QS interference molecules. This review highlights the utility of these methods for developing potential biomarkers against infectious Gram-positive pathogens.

Short-chain fatty acids reprogram metabolic profiles with the induction of reactive oxygen species production in human colorectal adenocarcinoma cells.

Short-chain fatty acids (SCFAs) exhibit anticancer activity in cellular and animal models of colon cancer. Acetate, propionate, and butyrate are the three major SCFAs produced from dietary fiber by gut microbiota fermentation and have beneficial effects on human health. Most previous studies on the antitumor mechanisms of SCFAs have focused on specific metabolites or genes involved in antitumor pathways, such as reactive oxygen species (ROS) biosynthesis. In this study, we performed a systematic and unbiased analysis of the effects of acetate, propionate, and butyrate on ROS levels and metabolic and transcriptomic signatures at physiological concentrations in human colorectal adenocarcinoma cells. We observed significantly elevated levels of ROS in the treated cells. Furthermore, significantly regulated signatures were involved in overlapping pathways at metabolic and transcriptomic levels, including ROS response and metabolism, fatty acid transport and metabolism, glucose response and metabolism, mitochondrial transport and respiratory chain complex, one-carbon metabolism, amino acid transport and metabolism, and glutaminolysis, which are directly or indirectly linked to ROS production. Additionally, metabolic and transcriptomic regulation occurred in a SCFAs types-dependent manner, with an increasing degree from acetate to propionate and then to butyrate. This study provides a comprehensive analysis of how SCFAs induce ROS production and modulate metabolic and transcriptomic levels in colon cancer cells, which is vital for understanding the mechanisms of the effects of SCFAs on antitumor activity in colon cancer.

Mechanosensitive Hydrolysis of ATP and ADP in Lamina Propria of the Murine Bladder by Membrane-Bound and Soluble Nucleotidases.

Prior studies suggest that urothelium-released adenosine 5'-triphosphate (ATP) has a prominent role in bladder mechanotransduction. Urothelial ATP regulates the micturition cycle through activation of purinergic receptors that are expressed in many cell types in the lamina propria (LP), including afferent neurons, and might also be important for direct mechanosensitive signaling between urothelium and detrusor. The excitatory action of ATP is terminated by enzymatic hydrolysis, which subsequently produces bioactive metabolites. We examined possible mechanosensitive mechanisms of ATP hydrolysis in the LP by determining the degradation of 1,N 6 -etheno-ATP (eATP) at the anti-luminal side of nondistended (empty) or distended (full) murine (C57BL/6J) detrusor-free bladder model, using HPLC. The hydrolysis of eATP and eADP was greater in contact with LP of distended than of nondistended bladders whereas the hydrolysis of eAMP remained unchanged during filling, suggesting that some steps of eATP hydrolysis in the LP are mechanosensitive. eATP and eADP were also catabolized in extraluminal solutions (ELS) that were in contact with the LP of detrusor-free bladders, but removed from the organ chambers prior to addition of substrate. The degradation of both purines was greater in ELS from distended than from nondistended preparations, suggesting the presence of mechanosensitive release of soluble nucleotidases in the LP. The released enzyme activities were affected differently by Ca2+ and Mg2+. The common nucleotidase inhibitors ARL67156, POM-1, PSB06126, and ENPP1 Inhibitor C, but not the alkaline phosphatase inhibitor (-)-p-bromotetramisole oxalate, inhibited the enzymes released during bladder distention. Membrane-bound nucleotidases were identified in tissue homogenates and in concentrated ELS from distended preparations by Wes immunodetection. The relative distribution of nucleotidases was ENTPD1 >> ENPP1 > ENTPD2 = ENTPD3 > ENPP3 = NT5E >> ENTPD8 = TNAP in urothelium and ENTPD1 >> ENTPD3 >> ENPP3 > ENPP1 = ENTPD2 = NT5E >> ENTPD8 = TNAP in concentrated ELS, suggesting that regulated ectodomain shedding of membrane-bound nucleotidases possibly occurs in the LP during bladder filling. Mechanosensitive degradation of ATP and ADP by membrane-bound and soluble nucleotidases in the LP diminishes the availability of excitatory purines in the LP at the end of bladder filling. This might be a safeguard mechanism to prevent over-excitability of the bladder. Proper proportions of excitatory and inhibitory purines in the bladder wall are determined by distention-associated purine release and purine metabolism.

Treatment of Muscle Cramps in Patients With Cirrhosis of Liver: A Systematic Review.

Background: Muscle cramps are witnessed in 22-88% of patients with cirrhosis of liver and frequently lead to sleep disturbance with an appalling impact on quality of life. Despite such a high prevalence, there is lack of evidence-based management protocol due to scarcity of trials on treatment options in the literature. This study aimed to review systematically the available therapeutic options for muscle cramps in patients with cirrhosis of liver. Methods: A systematic review of the relevant databases (PubMed, Scopus, Embase, and Web of Science) to identify treatments for muscle cramps in patients with hepatic cirrhosis was performed. Studies meeting the selection criteria were reviewed and assessed for risk of bias and analyzed. Results: Twenty-four publications were identified as eligible for inclusion in this systematic review. Seven randomized controlled trials (RCTs) and 17 prospective studies were included. Taurine, methocarbamol, baclofen, and orphenadrine are relatively safer and effective treatment option for muscle cramps in cirrhosis on the basis of recently conducted RCTs. Moreover, l-carnitine, branched-chain amino acids (BCAAs), pregabalin, zinc, and vitamin D are also safe and showed beneficial effects on muscle cramps. However, studies on vitamin E revealed contradictory results. Conclusion: Taurine, BCAAs, orphenadrine, and baclofen are safe and well-tolerated treatment options for muscle cramps in cirrhosis. However, well-designed randomized controlled clinical trials are the need of the hour to determine the most suitable treatment options for skeletal muscle cramps in patients with cirrhosis of liver.

Puerarin improves skeletal muscle strength by regulating gut microbiota in young adult rats.

Background: Sarcopenia is an age-related skeletal muscle dysfunction syndrome that is lacking validated treatments. Maximizing muscle strength in young adulthood may be a promising way to prevent sarcopenia in the elderly. The phytomolecule puerarin has been extensively used in clinical practice and reported to increase energy metabolism in skeletal muscle by directly targeting the skeletal muscle fiber. However, the bioavailability of puerarin is very poor, and almost 93% of puerarin stays in the intestine until excretion. Therefore, we hypothesize that puerarin may regulate gut microbiota to improve skeletal muscle strength and/or mass in adults. Methods: Twenty three-month old male Sprague Dawley rats were divided into two groups according to average weights, puerarin group (puerarin dissolved in 0.5% CMC-Na, 150 â€‹mg/kg/day, N â€‹= â€‹10), and control group (equal volume 0.5% CMC-Na, N â€‹= â€‹10). The treatment lasted for 8 weeks. Muscle weight, muscle fiber types and cross-sectional area (CSA), ex vivo muscle contraction test and grip strength were measured. 16S rDNA sequencing was employed to evaluate the gut microbiota composition in the sample of cecal content. Short-chain fatty acids (SCFAs) in cecal and serum were analyzed by gas chromatography-mass spectrometry. Adenosine triphosphate (ATP) concentration in skeletal muscle was also detected. Pearson's correlation was used to analyze the relations between SCFAs, ATP concentration and muscle function. Results: After puerarin treatment, grip strength, the specific twitch force, and the tetanic forces in the soleus (SOL) and extensor digitorum longus (EDL) muscle were significantly higher than those of the control group. The percentage and CSA of type II muscle fiber in EDL was higher in the puerarin group than those in the control group. Puerarin treatment significantly changed the gut microbial constitutes. Two SCFAs-productive microbiota, the families Peptococcaceae and Closteridiales, were significantly higher in the puerarin group than those in the control group, while the ratio of Prevotellaceae/Bacteroidaceae (P/B), a muscle atrophy indicator, was lower in the puerarin group. As expected, there were significant linear correlations between the concentrations of SCFAs, including cecal total SCFAs, serum n-butyric acid and total SCFAs, and skeletal muscle strength and function, including the twitch force and tetanic force of SOL and EDL, as well as the forelimb grip strength. Conclusion: In conclusion, puerarin improved the forelimb grip strength and muscle contraction function in young adult rats. The underlying mechanism may include that puerarin increased SCFAs production by regulating gut microbiota, augmented ATP synthesis and skeletal muscle strength. The translational potential of this article : Our study finds that a clinical used phytomolecule puerarin has the potential of improving skeletal muscle strength in young adult rats. As puerarin has long-term clinical experience and shows good safety, it might be a potential candidate for developing muscle strengthening agents.

Antidepressants induce toxicity in human placental BeWo cells.

Selective serotonin reuptake inhibitors (SSRIs), serotonin and noradrenaline reuptake inhibitors (SNRIs), and noradrenergic and specific serotonergic antidepressants (NaSSAs) are broadly used for the treatment of depression. Depression is one of the most common psychiatric disorders in pregnant women and SSRIs are commonly prescribed for depression during pregnancy. The placenta regulates the transport of nutrients and oxygen between the maternal and fetal circulation, and is essential for the survival and growth of the fetus. The present study investigated the effects of antidepressants on human placental BeWo cells. BeWo cell viability was significantly decreased following exposure to sertraline (SSRI), paroxetine (SSRI), fluvoxamine (SSRI), and duloxetine (SNRI), whereas escitalopram (SSRI), venlafaxine (SNRI), and mirtazapine (NaSSA) showed little or no effects. Extracellular lactate dehydrogenase activity was increased by sertraline, paroxetine, fluvoxamine, and duloxetine, indicating toxicity to the cells. Sertraline increased the production of cellular reactive oxygen species (ROS) and decreased the mitochondrial membrane potential. Sertraline decreased the cellular ATP content in a time and concentration-dependent manner. Caspase-3/7 activity and apoptotic cells, detected using the phosphatidylserine-specific fluorescent probe Apotracker Green, were increased by sertraline. Our findings suggest that antidepressants, such as sertraline, paroxetine, fluvoxamine, and duloxetine, induce toxicity in human placental BeWo cells. Sertraline may induce ROS-dependent apoptosis in human placental cells. These results are useful for further studies to determine the optimal dosage of antidepressants for pregnant women.