Effects of low-frequency ultrasound combined with anti-MRSA agents on the mouse model of pulmonary infection.

The treatment of methicillin-resistant Staphylococcus aureus (MRSA)-induced pneumonia with antibiotics alone poses considerable challenges. To address these challenges, low-frequency ultrasound (LFU) emerges as a promising approach. In this study, a mouse pneumonia model was established through intratracheal injection of MRSA to investigate the therapeutic efficacy of LFU in combination with antibiotics. Minimal inhibitory concentration was assessed, and the distribution of antibiotics in the lung and plasma was determined using liquid chromatography coupled with mass spectrometry. Various parameters, including the survival rate, histopathology, lung bacterial clearance, and the expressions of cytokines and inflammation-related genes, were evaluated before and after treatment. Compared with the infection group, both the antibiotic-alone groups [vancomycin (VCM), linezolid, and contezolid (CZD)] and the groups in combination with LFU demonstrated an improvement in the survival status of mice. The average colony-forming units of lung tissue in the LFU combination groups were lower compared with the antibiotic-alone groups. While no significant changes in C-reactive protein and procalcitonin in plasma and bronchoalveolar lavage fluid were observed, histopathological results revealed reduced inflammatory damage in LFU combination groups. The secretion of interleukin-6 and tumor necrosis factor-alpha was decreased by the combination treatment, particularly in the VCM + LFU group. Furthermore, the expressions of MRSA virulence factors (hla and agrA) and inflammation-related genes (Saa3, Cxcl9, and Orm1) were further reduced by the combinations of LFU and antibiotics. Additionally, LFU treatment facilitated the distribution of VCM and CZD in mouse lung tissue at 30 and 45 min, respectively, after dosage.IMPORTANCETreating pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA) with antibiotics alone poses significant challenges. In this in vivo study, we present compelling evidence supporting the efficacy of low-frequency ultrasound (LFU) as a promising approach to overcome these obstacles. Our findings demonstrated that LFU enhanced the effectiveness of vancomycin, linezolid, and contezolid in an MRSA pneumonia model. The combination of LFU with anti-MRSA agents markedly improved the survival rate of mice, accelerated the clearance of pulmonary bacteria, reduced inflammatory injury, inhibited the production of MRSA endotoxin, and enhanced the distribution of antibiotics in lung tissue. The application of LFU in the treatment of pulmonary infections held substantial significance. We believe that readers of your journal will find this topic of considerable interest.

Meta-analysis of efficacy of perioperative oral antibiotics in intestinal surgery with surgical site infection.

OBJECTIVES: Surgical site infection (SSI) is a serious complication of intestinal surgery. In this meta-analysis, we aimed to explore the efficacy and safety of different preoperative oral antibiotic preparation (OABP) compared with intravenous antibiotic preparation (IVAP) and/or mechanical bowel preparation (MBP). METHODS: A meta-analysis consisting of adult patients adopting oral antibiotics versus other regimens during the preoperative preparation of elective intestinal surgery was performed. The outcome included overall SSI, organ space SSI, superficial SSI, deep SSI, and mortality rate. RESULTS: A total of 35 randomized controlled trials (RCTs) consisting of 8445 adult patients were included in our present analysis. OABP regimens were combined with IVAP in 29 RCTs. In general, the incidence of overall SSI in the OABP group was less compared with the IVAP alone or IVAP+MBP group (RR 0.56, 95% CI 0.46-0.69, P < .00001, I2 = 47%). Metronidazoles plus quinolones or aminoglycosides showed the best effect on reducing the overall SSI. OABP in combination with preoperative and postoperative IVAP was both significantly associated with reduced SSI. IVAP before and within 24 h after surgery showed the best advantage. No difference was found between the OABP without IVAP group and the control group in reducing SSI. OABP regimens also demonstrated a lower incidence rate of organ space SSI, superficial SSI, deep SSI, and mortality. CONCLUSION: OABP in combination with preoperative IVAP and within 24 h post-operation significantly reduced the incidence of SSI in intestinal surgery. Metronidazoles accompanied with quinolones or aminoglycosides might be the appropriate combinations for OABP regimens.

M1ARegpred: Epitranscriptome Target Prediction of N1-methyladenosine (m1A) Regulators Based on Sequencing Features and Genomic Features.

BACKGROUND: N1-methyladenosine (m1A) is a reversible post-transcriptional modification in mRNA, which has been proved to play critical roles in various biological processes through interaction with different m1A regulators. There are several m1A regulators existing in the human genome, including YTHDF1-3 and YTHDC1. METHODS: Several techniques have been developed to identify the substrates of m1A regulators, but their binding specificity and biological functions are not yet fully understood due to the limitations of wet-lab approaches. Here, we submitted the framework m1ARegpred (m1A regulators substrate prediction), which is based on machine learning and the combination of sequence-derived and genome-derived features. RESULTS: Our framework achieved area under the receiver operating characteristic (AUROC) scores of 0.92 in the full transcript model and 0.857 in the mature mRNA model, showing an improvement compared to the existing sequence-derived methods. In addition, motif search and gene ontology enrichment analysis were performed to explore the biological functions of each m1A regulator. CONCLUSIONS: Our work may facilitate the discovery of m1A regulators substrates of interest, and thereby provide new opportunities to understand their roles in human bodies.

Testicular quantitative ultrasound: A noninvasive monitoring method for evaluating spermatogenic function in busulfan-induced testicular injury mouse models.

Busulfan-induced testicular injury mouse models are commonly used for experiments on spermatogonial stem cell transplantation, treatments for azoospermia due to spermatogenic failure and preserving male fertility after chemotherapy. Here, we investigated the value of testicular quantitative ultrasound for evaluating spermatogenic function in this model. In this study, testicular ultrasound was performed on mice from day 0 to 126 after busulfan treatment (n = 48), and quantitative data, including the testicular volume, mean pixel intensity and pixel uniformity, were analysed. The results revealed that from day 0 to 36, the testicular volume was positively associated with the testicle-to-body weight ratio (r = .92). On day 63, the pixel uniformity, which remained stable from day 0 to 36, declined significantly compared with that on day 36 (p < .01). On day 126, when the whole progression of spermatogenesis could be observed in most tubules, the mean pixel intensity also returned to normal (p > .05). In conclusion, testicular quantitative ultrasound could be used as a noninvasive and accurate monitoring method for evaluating spermatogenic function in busulfan-induced testicular injury mouse models.

A panel of extracellular vesicle long noncoding RNAs in seminal plasma for predicting testicular spermatozoa in nonobstructive azoospermia patients.

STUDY QUESTION: Whether the testis-specific extracellular vesicle (EV) long noncoding RNAs (lncRNAs) in seminal plasma could be utilized to predict the presence of testicular spermatozoa in nonobstructive azoospermia (NOA) patients? SUMMARY ANSWER: Our findings indicate that the panel based on seminal plasma EV lncRNAs was a sensitive and specific method in predicting the presence of testicular spermatozoa and may improve clinical decision-making of NOA. WHAT IS KNOWN ALREADY: The adoption of sperm retrieval techniques, especially microdissection testicular sperm extraction (mTESE), in combination with ICSI has revolutionized treatment for NOA. However, there are no precise and noninvasive methods for predicting whether there are testicular spermatozoa in NOA patients before mTESE. STUDY DESIGN, SIZE, DURATION: RNA sequencing was performed on seminal plasma EVs from 6 normozoospermic men who underwent IVF due to female factor and 5 idiopathic NOA patients who failed to obtain testicular spermatozoa by mTESE and were diagnosed as having Sertoli cell-only syndrome by postoperative pathology. A biomarker panel of lncRNAs was constructed and verified in 96 NOA patients who underwent mTESE. Decision-making process was established based on the panel in seminal plasma EVs from 45 normozoospermia samples, 43 oligozoospermia samples, 62 cryptozoospermia samples, 96 NOA samples. PARTICIPANTS/MATERIALS, SETTING, METHODS: RNA sequencing was done to examine altered profiles of EV lncRNAs in seminal plasma. Furthermore, a panel consisting of EV lncRNAs was established and evaluated in training set and validation sets. MAIN RESULTS AND THE ROLE OF CHANCE: A panel consisting of nine differentially expressed testis-specific lncRNAs, including LOC100505685, SPATA42, CCDC37-DT, GABRG3-AS1, LOC440934, LOC101929088 (XR_927561.2), LOC101929088 (XR_001745218.1), LINC00343 and LINC00301, was established in the training set and the AUC was 0.986. Furthermore, the AUC in the validation set was 0.960. Importantly, the panel had a unique advantage when compared with models based on serum hormones from the same group of NOA cases (AUC, 0.970 vs 0.723; 0.959 vs 0.687, respectively). According to the panel of lncRNAs, a decision-making process was established, that is when the score of an NOA case exceeds 0.532, sperm retrieval surgery may be recommended. LIMITATIONS, REASONS FOR CAUTION: In the future, the sample size needs to be further expanded. Meanwhile, the regulatory functions and mechanism of lncRNAs in spermatogenesis also need to be elucidated. WIDER IMPLICATIONS OF THE FINDINGS: When the score of our panel is below 0.532, subjecting the NOA patients to ineffective surgical interventions may not be recommended due to poor sperm retrieval rate. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the National Natural Science Foundation of China (81871110, 81971314 and 81971759); the Guangdong Special Support Plan-Science and Technology Innovation Youth Top Talents Project (2016TQ03R444); the Science and Technology Planning Project of Guangdong Province (2016B030230001 and 201707010394); the Key Scientific and Technological Program of Guangzhou City (201604020189); the Pearl River S&T Nova Program of Guangzhou (201806010089); the Transformation of Scientific and Technological Achievements Project of Sun Yat-sen University (80000-18843235) and the Youth Teacher Training Project of Sun Yat-sen University (17ykpy68 and 18ykpy09). There are no competing interests related to this study. TRIAL REGISTRATION NUMBER: N/A.

Inhibiting Necroptosis of Spermatogonial Stem Cell as a Novel Strategy for Male Fertility Preservation.

Fertility preservation is a common concern for male cancer survivors of reproductive age. However, except for testicular tissue cryopreservation, which is not very effective, there is no feasible and precise therapy capable of protecting spermatogenesis for prepubertal boys before or during gonadotoxic treatment. This study aims to investigate the effects of inhibiting necroptosis of spermatogonial stem cell (SSC) in fertility preservation. Male mice 12 weeks of age were used to establish gonadotoxicity with two intraperitoneal injections of busulfan at a total dose of 40 mg kg-1. The mouse model and the primary cultured mouse SSCs were used to characterize the relationship between necroptosis of SSC and gonadotoxicity. Meanwhile, the effects of an inhibitor of necroptosis pathway, RIPA-56, were observed on day 36 in the mouse model of busulfan-induced gonadotoxicity. We found that the number of SSCs was decreased, but the level of necroptosis was upregulated on day 18 after busulfan treatment in testes from gonadotoxic mice. Further experiments in primary cultured cells showed that the necroptosis caused cell death in busulfan-treated SSCs and could be inhibited by RIPA-56. After suppressing the necroptosis of SSCs, the busulfan-induced mice had a decreased loss of spermatogenic cells as shown by histology and an increased Johnsen's score. Moreover, the quantities of SSCs and epididymal spermatozoa were restored after intervention with RIPA-56, indicating a series of beneficial effects by targeting the necroptosis of SSCs in mice undergoing busulfan treatment. In conclusion, our findings reveal that the necroptosis of SSCs plays a critical role in busulfan-induced gonadotoxicity and may be a potential target for male fertility preservation.

Transcutaneous vagus nerve stimulation for the treatment of drug-resistant epilepsy: a meta-analysis and systematic review.

BACKGROUND: The transcutaneous vagus nerve stimulation (tVNS) is a newly developed non-invasive technique in the treatment of drug-resistant epilepsy and results in positive effects for patients who cannot tolerate invasive vagus nerve stimulation. In this study, we aim to define the relationship between tVNS and seizure control, quality of life (QOL) and some other factors. METHODS: We found articles by searching through PubMed and Web of Science, and a total of three articles with 280 patients overall were included. These eligible studies include two randomized double-blinded trials and one randomized single-blinded trial. Meta-analysis and systematic review were performed, analysing the association between tVNS and seizure frequency using the available data. The responder rate, QOL and adverse effects were also analysed. RESULTS: The results showed a significant difference in seizure frequency between treatment group and control group (Z = 2.14, P = 0.03, 95% confidence interval (CI) -6.31 to -0.27; I2 = 10%). However, only two studies provided the data of responders, and the result failed to figure out a significant difference (Z = 0.75, P = 0.45, 95% CI (odds ratio) 1.47 (0.54-4.02); I2 = 61%). It is difficult to define whether tVNS improved QOL between treatment and control groups using the available data. The adverse effects seem to be very few, with the most common being headache. CONCLUSION: tVNS is an effective procedure to control the frequency of seizures according to the available data, especially for those patients who do not want to tolerate a surgical procedure.

Establishing a nonlethal and efficient mouse model of male gonadotoxicity by intraperitoneal busulfan injection.

An ideal animal model of azoospermia would be a powerful tool for the evaluation of spermatogonial stem cell (SSC) transplantation. Busulfan has been commonly used to develop such a model, but 30%-87% of mice die when administered an intraperitoneal injection of 40 mg kg-1. In the present study, hematoxylin and eosin staining, Western blot, immunofluorescence, and quantitative real-time polymerase chain reaction were used to test the effects of busulfan exposure in a mouse model that received two intraperitoneal injections of busulfan at a 3-h interval at different doses (20, 30, and 40 mg kg-1) on day 36 or a dose of 40 mg kg-1 at different time points (0, 9, 18, 27, 36, and 63 days). The survival rate of the mice was 100%. When the mice were treated with 40 mg kg-1 busulfan, dramatic SSC depletion occurred 18 days later and all of the germ cells were cleared by day 36. In addition, the gene expressions of glial cell line-derived neurotrophic factor (GDNF), fibroblast growth factor 2 (FGF2), chemokine (C-X-C Motif) ligand 12 (CXCL12), and colony-stimulating factor 1 (CSF1) were moderately increased by day 36. A 63-day, long-term observation showed the rare restoration of endogenous germ cells in the testes, suggesting that the potential period for SSC transplantation was between day 36 and day 63. Our results demonstrate that the administration of two intraperitoneal injections of busulfan (40 mg kg-1 in total) at a 3-h interval to mice provided a nonlethal and efficient method for recipient preparation in SSC transplantation and could improve treatments for infertility and the understanding of chemotherapy-induced gonadotoxicity.

Transplantation of Human Urine-Derived Stem Cells Ameliorates Erectile Function and Cavernosal Endothelial Function by Promoting Autophagy of Corpus Cavernosal Endothelial Cells in Diabetic Erectile Dysfunction Rats.

AIMS: Cavernosal endothelial dysfunction is one of the factors in developing diabetic erectile dysfunction (DED), but the mechanism of cavernosal endothelial dysfunction is unclear. The present study is aimed at determining the contribution of autophagy in cavernosal endothelial dysfunction of DED rats and explaining the therapeutic effect of urine-derived stem cells (USCs). METHODS: After rat corpus cavernosal vascular endothelial cells (CCECs) were isolated and cultured in vitro, CCECs were treated with advanced glycation end products (AGEs) to mimic the diabetic situation. Autophagy flux, proliferation, and apoptosis of CCECs were determined by mRFP-GFP-LC3 adenovirus infection combined with fluorescence observation and western blot analysis. USCs were isolated from the urine of six healthy male donors, and coculture systems of USCs and CCECs were developed to assess the protective effect of USCs for CCECs in vitro. The contribution of autophagy to the cellular damage in CCECs was evaluated by the autophagic inhibitor, 3-methyladenine (3-MA). Then, DED rats were induced by streptozotocin (50 mg/kg) and screened by apomorphine test (100 µg/kg). In DED rats, USCs or PBS as vehicle was administrated by intracavernous injection (n = 15 per group), and another 15 normal rats served as normal controls. Four weeks after injection, erectile function was evaluated by measuring the intracavernosal pressure (ICP) and mean arterial pressure (MAP). Cavernosal endothelial function and autophagic activity were examined by western blot, immunofluorescence, and transmission electron microscopy. RESULTS: In vitro, AGE-treated CCECs displayed fewer LC3 puncta formation and expressed less LC3-II, Beclin1, and PCNA but expressed more p62 and cleaved-caspase3 than controls (p < 0.05). Coculture of USCs with CCECs demonstrated that USCs were able to protect CCECs from AGE-induced autophagic dysfunction and cellular damage, which could be abolished by 3-MA (p < 0.05). DED rats showed lower ratio of ICP/MAP, reduced expression of endothelial markers, and fewer autophagic vacuoles in the cavernosal endothelium when compared with normal rats (p < 0.05). Intracavernous injection of USCs improved erectile function and cavernosal endothelial function of DED rats (p < 0.05). Most importantly, our data showed that the repaired erectile function and cavernosal endothelial function were the result of restored autophagic activity of the cavernosal endothelium in DED rats (p < 0.05). CONCLUSIONS: Impaired autophagy is involved in the cavernosal endothelial dysfunction and erectile dysfunction of DED rats. Intracavernous injection of USCs upregulates autophagic activity in the cavernosal endothelium, contributing to ameliorating cavernosal endothelial dysfunction and finally improving the erectile dysfunction induced by diabetes.

Urine-Derived Stem Cells Facilitate Endogenous Spermatogenesis Restoration of Busulfan-Induced Nonobstructive Azoospermic Mice by Paracrine Exosomes.

Nonobstructive azoospermia (NOA) is a severe form of male infertility, with limited effective treatments. Urine-derived stem cells (USCs) possess multipotent differentiation capacity and paracrine effects, and participate in tissue repair and regeneration. The aim of this study is to investigate whether the transplantation of USCs or USC exosomes (USC-exos) could promote endogenous spermatogenesis restoration in a busulfan-induced NOA mice model. USCs were cultured and characterized by flow cytometry. High-density USCs were cultured in a hollow fiber bioreactor for exosomes collection. USC-exos were isolated from USCs conditional media and identified by transmission electron microscopy, western blotting, and Flow NanoAnalyzer analysis. USC-exos exhibited sphere- or cup-shaped morphology with a mean diameter of 66.5 ± 16.0 nm, and expressed CD63 and CD9. USCs and USC-exos were transplanted into the interstitial space in the testes of NOA mice per the following groups: normal group; groups treated with no injection, phosphate-buffered saline (PBS), USCs or USC-exos on days 3 and 36 after busulfan administration, respectively. Thirty days after USCs and USC-exos transplantation, spermatogenesis was restored by both USCs and USC-exos in NOA mice 36 days after busulfan treatment as confirmed by immunofluorescence staining and hematoxylin and eosin staining. Moreover, spermatogenic genes (Pou5f1, Prm1, SYCP3, and DAZL) and the spermatogenic protein UCHL1 were significantly increased in both the USCs 36 and USC-exos36 groups compared with the PBS group, as demonstrated using quantitative real-time polymerase chain reaction and western blot analysis. However, the transplantation of USCs or USC-exos at day 3 after busulfan treatment did not improve spermatogenesis in NOA mice. Our study demonstrated that USCs could facilitate endogenous spermatogenesis restoration of busulfan-induced NOA mice through paracrine exosomes but could not protect the mouse testicles at the early stage of destruction caused by busulfan. This study provides a novel insight into the treatment of NOA.

Extracellular Vesicles From Human Urine-Derived Stem Cells Ameliorate Erectile Dysfunction in a Diabetic Rat Model by Delivering Proangiogenic MicroRNA.

INTRODUCTION: Stem cell therapies represent a promising new frontier for the treatment of refractory diabetic erectile dysfunction (DED). The use of stem cell-derived extracellular vesicles (EVs) is a novel strategy for cell-free stem cell therapy. We have reported that urine-derived stem cells (USCs) can improve DED; however, the therapeutic effects of EVs secreted by USCs (USC-EVs) remain unknown. AIM: To determine the therapeutic effects of USC-EVs on DED in a rat model. METHODS: USC-EVs were isolated from conditioned medium by ultracentrifugation. DED was induced in male Sprague-Dawley rats via an intraperitoneal injection of streptozotocin. Sixteen DED rats were divided into phosphate-buffered saline (PBS) and USC-EV groups. Eight normal rats served as the normal control group. PBS or USC-EVs were transplanted into the corpora cavernosa in the corresponding groups. MAIN OUTCOME MEASURE: Intracavernosal pressure (ICP), mean arterial pressure (MAP), expression of endothelial markers (CD31), endothelial nitric oxide synthase (eNOS), phospho-eNOS, and neural nitric oxide synthase (nNOS) were assessed in each group. Masson's trichrome staining was used to determine the collagen deposition and ratio of smooth muscle cells to collagen. The microRNA (miRNA) cargo of USC-EVs was characterized by high-throughput RNA sequencing. RESULTS: Recovery of erectile function was observed in the USC-EV group, as represented by improved ICP and ICP/MAP ratio. CD31, eNOS, phospho-eNOS, and nNOS expression in the penis was significantly improved in the USC-EV group. In addition, the ratio of smooth muscle to collagen was significantly increased in the USC-EV group. RNA sequencing revealed that USC-EVs were enriched for distinct classes of miRNA (miR-21-5p, let-7 family, miR-10 family, miR-30 family, and miR-148a-3p) that promote angiogenesis. CONCLUSION: USC-EV transplantation can ameliorate DED in rats. Its mechanism may involve the delivery of proangiogenic miRNA. Ouyang B, Xie Y, Zhang C, et al. Extracellular Vesicles From Human Urine-Derived Stem Cells Ameliorate Erectile Dysfunction in a Diabetic Rat Model by Delivering Proangiogenic MicroRNA. Sex Med 2019;7:241-250.

Total and Nonheme Dietary Iron Intake Is Associated with Metabolic Syndrome and Its Components in Chinese Men and Women.

The causal relationship between serum ferritin and metabolic syndrome (MetS) remains inconclusive. Dietary iron intake increases serum ferritin. The objective of this study was to evaluate associations of total, heme, and nonheme dietary iron intake with MetS and its components in men and women in metropolitan China. Data from 3099 participants in the Shanghai Diet and Health Survey (SDHS) obtained during 2012⁻2013 were included in this analysis. Dietary intake was assessed by 24-h diet records from 3 consecutive days. Multivariate generalized linear mixed models were used to evaluate the associations of dietary iron intake with MetS and its components. After adjustment for potential confounders as age, sex, income, physical exercise, smoking status, alcohol use, and energy intake, a positive trend was observed across quartiles of total iron intake and risk of MetS (p for trend = 0.022). Compared with the lowest quartile of total iron intake (<12.72 mg/day), the highest quartile (≥21.88 mg/day) had an odds ratio (95% confidence interval), OR (95% CI), of 1.59 (1.15,2.20). In addition, the highest quartile of nonheme iron intake (≥20.10 mg/day) had a 1.44-fold higher risk of MetS compared with the lowest quartile (<11.62 mg/day), and higher risks of MetS components were associated with the third quartiles of total and nonheme iron intake. There was no association between heme iron intake and risk of MetS (p for trend = 0.895). Associations for total and nonheme iron intake with MetS risk were found in men but not in women. Total and nonheme dietary iron intake was found to be positively associated with MetS and its components in the adult population in metropolitan China. This research also revealed a gender difference in the association between dietary iron intake and MetS.

Evaluation of Nutritional Compositions, Bioactive Compounds, and Antioxidant Activities of Shanxi Aged Vinegars During the Aging Process.

Shanxi aged vinegar (SAV) is known as famous fermented food in China. During the brewing process, a large number of nutritional substances and bioactive compounds are produced, which have beneficial effects on human body. In this study, the contents of nutritional compositions including proteins, fats, carbohydrates, organic acids, and amino acids were determined in SAV samples. The antioxidant compounds and properties of SAV with different aging time were also evaluated. The results showed that the contents of proteins, crude fats, and carbohydrates in SAV were not changed with the aging time. Moreover, Alanine was the main component of amino acids in SAV, and the total contents of amino acids were increased with the aging time. Acetic acid and lactic acid were the predominant organic acids in SAV. The contents of acetic acid and lactic acid accounted for more than 90% of the total organic acids in SAV, which were increased during the aging process of 5 years. Furthermore, total phenols, flavonoids contents, and browning index in SAV were also increased during the aging time. These antioxidant compounds showed a high correlation with the antioxidant activities of SAV measured by ferric reducing antioxidant power and 2,2'-azino-bis(3-ethylbenzthi azoline-6-sulfonic acid) assays. The contribution of polyphenolic fractions and high molecular weight melanoidins to total antioxidant activities was similar (about 49% and 48%, respectively). Our findings would provide new insights to further explore the development of new vinegar-based functional foods. PRACTICAL APPLICATION: The analysis of nutritional compositions, bioactive compounds, and antioxidant capacities in vinegars provides a theoretical basis for the function of SAV. It also provides references for further explore the development of new-type functional and healthy vinegars.

Shanxi Aged Vinegar Protects against Alcohol-Induced Liver Injury via Activating Nrf2-Mediated Antioxidant and Inhibiting TLR4-Induced Inflammatory Response.

Shanxi aged vinegar (SAV) is a typical fermented and antioxidant food, which has various health-promoting effects. This work aimed to explore the effects of SAV on alcohol-induced liver injury. A mice model of alcoholic liver injury was established to illuminate its potential mechanisms. All mice pretreated with SAV and then received an ethanol solution (50% w/v, 4.8 g/kg b.w.). The results showed that SAV ameliorated alcohol-induced histological changes and elevation of liver enzymes. SAV attenuated alcohol-induced oxidative stress by declining levels of hepatic oxidants, and restoring depletion of antioxidant enzyme activities in mice livers. Moreover, SAV alleviated alcohol-induced oxidative damage by activating nuclear factor erythroid-2-related factor 2 (Nrf2)-mediated signal pathway. In addition, SAV prevented alcohol-induced inflammation by suppressing lipopolysaccharide (LPS) level and activities of pro-inflammatory enzymes, and regulating inflammatory cytokines. SAV inhibited alcohol-induced inflammation through down-regulating the expression of Toll-like receptor 4 (TLR4)-mediated inflammatory response. The findings provide crucial evidence for elucidating the hepatoprotective mechanisms of SAV and encourage the future application of SAV as a functional food for liver protection.

Ginsenoside Rh2 and Rg3 inhibit cell proliferation and induce apoptosis by increasing mitochondrial reactive oxygen species in human leukemia Jurkat cells.

Ginsenoside Rh2 (GRh2) and ginsenoside Rg3 (GRg3) are primary bioactive components in Panax ginseng. The present study aimed to investigate the underlying mechanisms of apoptotic cell­death induced by GRh2 and GRg3 in human leukemia Jurkat cells. The Cell Counting kit­8 assay was used to determine cell proliferation. Apoptosis was detected by nuclear morphologic observation by Hoechst 33342 staining and Annexin V-allophycocyanin and 7-amino-actinomycin D assay. mitoTEMPO, a mitochondrial reactive oxygen species (ROS) scavenger, was used to examine the effects of mitochondrial ROS on cell viability and mitochondrial membrane potential (MMP). Finally, the expression levels of numerous mitochondrial­associated apoptosis proteins were assessed by western blot analysis. These results demonstrated that GRh2 and GRg3 inhibited cell growth and induced apoptosis, and that GRh2 had greater cytotoxicity than GRg3. GRh2 induced generation of more mitochondrial ROS compared with GRg3 in Jurkat cells; however, this effect was ameliorated by subsequent treatment with mitoTEMPO. Furthermore, excess mitochondrial ROS induced by GRh2 was more potent than GRg3 in inhibiting cell proliferation and reducing MMP. In addition, expression levels of apoptosis­associated proteins were significantly increased in Jurkat cells treated with GRh2 than GRg3. In conclusion, these findings suggested that GRh2 and GRg3 induce mitochondrial-associated apoptosis by increasing mitochondrial ROS in human leukemia Jurkat cells. GRh2 may more effectively inhibit cell growth and accelerate apoptosis than GRg3. This study provides a potential novel strategy for the treatment of acute lymphoblastic leukemia.

Gallic acid induces apoptosis and enhances the anticancer effects of cisplatin in human small cell lung cancer H446 cell line via the ROS-dependent mitochondrial apoptotic pathway.

Small cell lung cancer (SCLC) is the most aggressive lung cancer subtype and accounts for more than 15% of all lung cancer cases. Cisplatin [cis-diamminedichloroplatinum (CDDP)]-based combination chemotherapy is the cornerstone for all stages of SCLC. However, acquired multidrug resistance (MDR) and intolerable toxicities lead to a high mortality rate in SCLC patients. Gallic acid [3,4,5-trihydroxybenzoic acid (GA)] is a natural botanic phenolic compound which can induce cell apoptosis in several types of cancers. In the present study, we aimed to explore the anticancer effects of GA on human SCLC H446 cells and its promotive effects on the anticancer activities of cisplatin. The viability of the H446 cells was analyzed by MTT assay. Morphological changes in the H446 cells were observed under an inverted microscope. Apoptosis induction was determined by Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) staining. The level of reactive oxygen species (ROS) was assessed by 2'7'-dichlorofluorescein diacetate (DCFH­DA), mitochondrial membrane potential (MMP) by JC-1, and western blotting was used to examine the expression of mitochondrial apoptosis-related proteins. The results showed that both GA and cisplatin changed the morphology, inhibited the growth and induced apoptosis in the H446 cells by inducing generation of ROS, disruption of MMP, downregulation of XIAP expression, and upregulation of Bax, Apaf-1, DIABLO and p53 expression. More importantly, GA combined with cisplatin exhibited synergistic effects on inducing of these pro-apoptotic mediators and modulating the activation of apoptosis-related molecules. However, inhibition of the generation of ROS by N-acetyl-l-cysteine (NAC), a specific ROS inhibitor, reversed the cell apoptosis induced by cisplatin combined with GA. In conclusion, the results from the present study revealed that GA exhibited an anticancer effect on human SCLC H446 cells and enhanced the antitumor activities of cisplatin via the ROS-dependent mitochondrial apoptotic pathway.

[Nutritional risk screening and enteral nutrition in patients with oral and maxillofacial cancers].

PURPOSE: To screen the nutritional risk of patients with oral and maxillofacial cancers using NRS2002 and evaluate the clinical usefulness of NRS2002. Meanwhile, nutritional support was given after screening and the effect was evaluated. METHODS: Fifty-nine patients with oral and maxillofacial cancers were enrolled in this study. The medical history and the intake condition of all patients were recorded, body weight and height were measured.The serum hemoglobin (Hb), lymphocyte count (LC), albumin (Alb), pre-albumin (PA) of the patients were detected. According to the requirements of NRS2002, the patients were screened before and after surgery. The patients with nutritional risks were divided into experimental group and control group randomly. The blood biochemical parameters in the two groups were compared after nutritional intervention. The data was analyzed by student's t test and Chi-square test with SPSS11.5 software package. RESULTS: Nutritional risk pre-operatively was 27.1% while the figure increased to 71.2% after operation (P < 0.05). Compared to pre-operation, nutritional risk increased significantly. Hb, LC, Alb and PA decreased significantly (P < 0.01). Before nutritional intervention,there was no difference of the biochemical stats between the patients in the experimental group and the control group (P > 0.05). After 7 days' treatment, the biochemical parameters except Hb and PA increased significantly in the control group. In the experimental group, LC, Alb and PA increased significantly (P < 0.05), especially Alb (P < 0.01), but Hb decreased. Compared with the control group, the NRS 2002 score decreased significantly in the experimental group after nutritional intervention. CONCLUSIONS: NRS2002 can reflect the nutritional risk of the patients with oral and maxillofacial cancers conveniently and swiftly. Nutritional support after operation can significantly increase the nutritional status of the patients, reduce the infectious complications and improve the prognosis.