Perilipin 5 protects the mitochondrial oxidative functions and improves the alcoholic liver injury in mice.

BACKGROUND AND AIMS: Alcohol consumption is a well-established risk factor for the onset and progression of hepatic steatosis. Perilipin 5 (Plin5), a lipid droplet protein, is an important protective factor against hepatic lipotoxicity induced by excessive lipolysis, but its role and molecular mechanism in alcoholic liver disease (ALD) are not fully elucidated. METHODS: The optimized National Institute on Alcohol Abuse and Alcoholism model was used to construct ALD model mice. Automatic biochemical analyser was used for Biochemical Parameters. The primary hepatocytes and Plin5-overexpressed HepG2 cells (including full-length Plin5 and Plin5 deleting 444-464 aa) were used for in vitro experiment. Haematoxylin and Eosin staining, Oil Red O staining, Bodipy 493/503 staining, Periodic Acid-Schiff staining, immunohistochemistry and JC-1 staining were used to evaluate cell morphology, lipids, glycogen, inflammation and membrane potential. Commercially kits are used to detect glycolipid metabolites, such as triglycerides, glycogen, glucose, reactive oxygen species, lactic acids, ketone bodies. Fluorescently labelled deoxyglucose, NBDG, was used for glucose intake. An XF96 extracellular flux analyser was used to determinate oxygen consumption rate in hepatocytes. The morphological and structural damage of mitochondria was evaluated by electron microscopy. Classical ultracentrifugation is used to separate the subcellular organelles of tissues and cells. Immunoblotting and qPCR were used to detect changes in mRNA and protein levels of related genes. RESULTS: Our results showed that the expression of Plin5 in mouse livers was enhanced by alcohol intake, and Plin5 deficiency aggravated the alcohol-induced liver injury. To clarify the mechanism, we found that Plin5 deficiency significantly elevated the hepatic NADH levels and ketone body production in the alcohol-treated mice. As NADH elevation could promote the reduction of pyruvate into lactate and then inhibit the gluconeogenesis, alcohol-treated Plin5-deficient mice exhibited more lactate production and severer hypoglycemia. These results implied that Plin5 deficiency impaired the mitochondrial oxidative functions in the presence of alcohol. In addition, we demonstrated that Plin5 could be recruited onto mitochondria by alcohol, while Plin5 without mitochondrial targeting sequences lost its mitochondrial protection functions. CONCLUSION: Collectively, this study demonstrated that the mitochondrial Plin5 could protect the alcohol-induced mitochondrial injury, which provides an important new insight on the roles of Plin5 in highly oxidative tissues.

Deafness gene screening based on a multilevel cascaded BPNN model.

Sudden sensorineural hearing loss is a common and frequently occurring condition in otolaryngology. Existing studies have shown that sudden sensorineural hearing loss is closely associated with mutations in genes for inherited deafness. To identify these genes associated with deafness, researchers have mostly used biological experiments, which are accurate but time-consuming and laborious. In this paper, we proposed a computational method based on machine learning to predict deafness-associated genes. The model is based on several basic backpropagation neural networks (BPNNs), which were cascaded as multiple-level BPNN models. The cascaded BPNN model showed a stronger ability for screening deafness-associated genes than the conventional BPNN. A total of 211 of 214 deafness-associated genes from the deafness variant database (DVD v9.0) were used as positive data, and 2110 genes extracted from chromosomes were used as negative data to train our model. The test achieved a mean AUC higher than 0.98. Furthermore, to illustrate the predictive performance of the model for suspected deafness-associated genes, we analyzed the remaining 17,711 genes in the human genome and screened the 20 genes with the highest scores as highly suspected deafness-associated genes. Among these 20 predicted genes, three genes were mentioned as deafness-associated genes in the literature. The analysis showed that our approach has the potential to screen out highly suspected deafness-associated genes from a large number of genes, and our predictions could be valuable for future research and discovery of deafness-associated genes.

Prokaryotic and eukaryotic promoters identification based on residual network transfer learning.

Promoters contribute to research in the context of many diseases, such as coronary heart disease, diabetes and tumors, and one fundamental task is to identify promoters. Deep learning is widely used in the study of promoter sequence recognition. Although deep models have fast and accurate recognition capabilities, they are also limited by their reliance on large amounts of high-quality data. Therefore, we performed transfer learning on a typical deep network based on residual ideas, called a deep residual network (ResNet), to solve the problem of a deep network's high dependence on large amounts of data in the process of promoter prediction. We used binary one-hot encoding to represent the promoter and took advantage of ResNet to extract feature representations from organisms with a large amount of promoter data. Then, we transferred the learned structural parameters to target organisms with insufficient promoter data to improve the generalization performance of ResNet in target organisms. We evaluated the promoter datasets of four organisms (Bacillus subtilis, Escherichia coli, Saccharomyces cerevisiae and Drosophila melanogaster). The experimental results showed that the AUCs of ResNet's promoter prediction after deep transfer were 0.8537 and 0.8633, which increased by 0.1513 and 0.1376 in prokaryotes and eukaryotes, respectively.

A 2-step algorithm combining glutamate dehydrogenase and nucleic acid amplification tests for the detection of Clostridioides difficile in stool specimens.

The optimized diagnosis algorithm of Clostridioides difficile infection (CDI) is worldwide concerns. The purpose of this study was to assess the toxigenic C. difficile test performance and propose an optimal laboratory workflow for the diagnosis of CDI in mild virulent epidemic areas. Diarrhea samples collected from patients were analyzed by glutamate dehydrogenase (GDH), toxin AB (CDAB), and nucleic acid amplification test (NAAT). We assessed the performance of GDH, the GDH-CDAB algorithm, and the GDH-NAAT algorithm using toxigenic culture (TC) as a reference method. In this study, 186 diarrhea samples were collected. The numbers of TC-positive and TC-negative samples were 39 and 147, respectively. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and kappa of the GDH assay were 100%, 80.3%, 57.4%, 100%, and 0.63; of the GDH-CDAB algorithm were 48.7%, 97.3%, 82.6%, 87.7%, and 0.54; and of the GDH-NAAT algorithm were 74.4%, 100%, 100%, 93.6%, and 0.82, respectively. The GDH-NAAT algorithm has great concordance with TC in detecting toxigenic C. difficile (kappa = 0.82), while the sensitivity of the GDH-CDAB algorithm was too low to meet the demand of CDI diagnosis clinically. GDH-NAAT algorithm is recommended for the detection of toxigenic C. difficile with high specificity, increased sensitivity, and cost-effective.

Jmjd maintains the morphology and function of lipid droplets and mitochondria of brown adipocytes in mice. / Jmjd3ç»´æŒå°é¼ æ£•è‰²è„‚è‚ªç»†èƒžè„‚æ»´åŠçº¿ç²’ä½“çš„å½¢æ€å’ŒåŠŸèƒ½.

OBJECTIVES: Jmjd3 can promote the differentiation of brown adipocytes, but its role in the ultrastructure of lipid droplets and mitochondria, the two key thermogenic organelles, is still unclear. The aim of this study is to investigate the effects of histone H3K27me3 demethylase Jmjd3 deletion on lipid droplets and mitochondria in brown adipocytes in mice. METHODS: Jmjd3 general knockout (Jmjd3-/-) mice and adipose tissue specific conditional knockout (Jmjd3F/FFabp4-Cre+) mice were constructed.Brown adipose tissue (BAT) was taken from the back of Jmjd3-/- and their littermates (Jmjd3+/+) at the 19.5 days of embryo (E19.5). BAT was also taken from the back of 6-week-old Jmjd3F/FFabp4-Cre+ and their littermates (Jmjd3flox/+or Jmjd3+/+Fabp4-Cre+). The morphology of brown adipocytes was observed by light microscopy after HE staining. The ultrastructure of lipid droplets and mitochondria was observed by electron microscopy. Western blotting was used to detect the expression of H3K27me3, Jmjd3, and uncouple protein 1 (UCP1) in BAT. RT-qPCR was used to detect the expression of Jmjd3, peroxisome proliferator-activated receptor γ (PPARγ), fatty acid binding protein 4 (Fabp4), UCP1, PR domain-containing 16 (PRDM16), cell death-inducing DFFA-like effector a (CIDEa), mitochondrial transcription factor A (TFAM), peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1α), mitochondrial cytochrome c oxidase subunit I (COX1), and cytochrome c (Cyt c). ATP content in the BAT was tested. The body temperature of Jmjd3F/FFabp4-Cre+ and their control mice during cold stimulation was detected. RESULTS: Two types of Jmjd3 knockout (Jmjd3-/- and Jmjd3F/FFabp4-Cre+) mice were smaller than their littermates. The expression of Jmjd3 mRNA (P<0.05) and protein in BAT was significantly decreased, and the protein expression of H3K27me3 was increased, indicating that the knockout mice were successfully constructed. HE staining showed that lipid droplets in BAT of Jmjd3-/- mice were significantly less than those in the control group. The results of electron microscopy showed that the area of brown adipocytes in Jmjd3-/- mice was smaller (P<0.05), the number of lipid droplets was less (P<0.01), and the size of lipid droplets was not significantly different (P>0.05). Mitochondrial edema and cristae rupture were observed in the Jmjd3-/- group.The number and area of mitochondria were not affected (both P>0.05), the number of mitochondrial cristae was significantly less than that of the control group (P<0.05). The protein expression of UCP1 of Jmjd3-/- mice was decreased. The mRNA expression of UCP1, CIDEa, and PGC-1α in BAT of Jmjd3-/- mice was significantly less than that of the control group (all P<0.05). ATP content in BAT of Jmjd3-/- mice was decreased (P<0.05). HE staining showed that lipid droplets in BAT of Jmjd3F/FFabp4-Cre+ mice were larger than those in the control group. Electron microscopy showed that there was no significant difference in size of adipocytes between the 2 groups (P>0.05). In the Jmjd3F/FFabp4-Cre+ mice, lipid droplets were less (P<0.05), but their diameters were larger (P<0.001). Mitochondrial edema and cristae rupture were observed in the Jmjd3F/FFabp4-Cre+ mice. The number of mitochondrial cristae in the Jmjd3F/FFabp4-Cre+ mice was significantly less than that in the control group (P<0.05). The protein expression of UCP1 in Jmjd3F/FFabp4-Cre+ mice was decreased. The mRNA expression of UCP1, PRDM16, CIDEa, COX1, PGC-1α in BAT of Jmjd3F/FFabp4-Cre+ mice was significantly less than that of the control group (all P<0.05). ATP content in BAT of Jmjd3F/FFabp4-Cre+ mice was decreased (P<0.05). In the Jmjd3F/FFabp4-Cre+ mice, the body temperature was decreased more and the cold tolerance was poor (P<0.05). CONCLUSIONS: Jmjd3 promotes the differentiation of brown adipocytes by enhancing the formation of lipid droplets in mouse brown adipocytes and maintaining the normal morphology and function of mitochondria.

Plin3 protects against alcoholic liver injury by facilitating lipid export from the endoplasmic reticulum.

Hepatic lipid accumulation is the most common pathological characteristic of alcoholic liver disease (ALD). In mammalian cells, excess neutral lipids are stored in lipid droplets (LDs). As a member of perilipin family proteins, Plin3 was recently found to regulate the LD biogenesis. However, the roles and mechanism of Plin3 in ALD progression remain unclear. Herein, we found that alcohol stimulated Plin3 expression in both mouse livers and cultured AML12 mouse hepatic cells, which was accompanied by excess LD accumulation in hepatocytes. The elevations of Plin3 in alcohol-treated hepatocytes paralleled with the levels of both PPARα and γ, and the protein degradation of Plin3 was also reduced after alcohol exposure. Moreover, Plin3 knockdown increased cellular sensitivity to alcohol-induced apoptosis, endoplasmic reticulum (ER) stress, and inflammatory cytokines release, including TNF-α, IL-1, and IL-6ß. Notably, alcohol exacerbated triglycerides (TG) accumulation in the ER and caused ER dilation in Plin3-knockdown AML12 cells. Finally, we observed that Plin3 interacted with dynein subunit Dync1i1 and mediated the colocalization of LDs and microtubules, while high concentration of alcohol disrupted microtubules and caused dispersion of excess small LDs in cytoplasm. Summarily, Plin3 promotes lipid export from the ER and reduces ER lipotoxic stress, thereby, protecting against alcoholic liver injury. Moreover, Plin3 could be an adapter protein mediating LD transport by microtubules. This study explored the roles of Plin3 in alcohol-induced hepatic injury, suggesting Plin3 as a potential target for the prevention of ALD progression.

GSK126 alleviates the obesity phenotype by promoting the differentiation of thermogenic beige adipocytes in diet-induced obese mice.

A close relationship between epigenetic regulation and obesity has been demonstrated in several recent studies. Histone methyltransferase enhancer of Zeste homolog 2 (Ezh2), which mainly catalyzes trimethylation of histone H3K27 to form H3K27me3 was found to be required for the differentiation of white and brown adipocytes in vitro. Here, we investigated the effects of the Ezh2-specific inhibitor GSK126 in a mouse model of obesity induced by a high-fat diet (HFD). We found that GSK126 treatment reduced body fat, improved glucose tolerance, increased lipolysis and improved cold tolerance in mice by promoting the differentiation of thermogenic beige adipocytes. Moreover, we discovered that GSK126 inhibited the differentiation of white adipocytes, and the decrease of Ezh2 enzymatic activity and H3K27me3 also changed the morphology of brown adipocytes but did not alter the expression of thermogenic genes in these cells. Our results indicated that GSK126 was a novel chemical inducer of beige adipocytes and may be a potential therapeutic agent for the management of obesity. Furthermore, they also prompted that Ezh2 and H3K27me3 play different roles in the differentiation of the white, brown, and beige adipocytes in vivo.

Cidec promotes the differentiation of human adipocytes by degradation of AMPKα through ubiquitin-proteasome pathway.

BACKGROUND: We previously showed that Cidec was localized on the surface of lipid droplets and could promote the differentiation of human adipocytes, but the molecular mechanism was still unknown. METHODS & RESULTS: In this study, we first sought to identify proteins that interact with Cidec using yeast two-hybrid system. The results revealed that Cidec could directly interact with AMPKα1 subunit. We further showed that AMPKα levels decreased while Cidec increased during the adipogenic differentiation of human adipocytes. Meanwhile, we observed that the increased Cidec could reduce AMPKα level in adipocytes, and the downregulation of AMPKα could help to promote the differentiation of adipocytes. The results of co-immunoprecipitation and immunofluorescent proved that Cidec biochemically interacted and co-localized with AMPKα1, which meant Cidec was a regulator for AMPKα stability through an ubiquitin-proteasome pathway. CONCLUSION: Our data suggested that Cidec could interact with and down-regulate AMPKα through an ubiquitin-proteasome degradation pathway, which provided a possible mechanism of Cidec in promoting human adipocytes differentiation. GENERAL SIGNIFICANCE: Our work proposed a new possible mechanism for human adipogenesis, and also provided a potential role of AMPKα as a target in treating obesity or obesity-related diseases.

Perilipin 5 improves hepatic lipotoxicity by inhibiting lipolysis.

UNLABELLED: Abnormal metabolism of nonesterified fatty acids (NEFAs) and their derivatives has been reported to be the main cause of intracellular lipotoxic injury. Normally, NEFAs are stored in lipid droplets (LDs) in the form of triglyceride (TG), which could reduce the lipotoxicity of cytosolic NEFAs. Previous studies have implicated that Perilipin 5 (Plin5), an LD-binding protein, regulates the storage and hydrolysis of TG in LD. However, its roles and underlying mechanisms in the liver remain unknown. Here we found that Plin5 expression was increased in steatotic livers. Using Plin5 knockout mice, we found that Plin5 deficiency resulted in reduced hepatic lipid content and smaller-sized LDs, which was due to the elevated lipolysis rate and fatty acid utilization. Plin5-deficient hepatocytes showed increased mitochondria proliferation, which could be explained by the increased expression and activity of PPARα stimulated by the increased NEFA levels. Meanwhile, Plin5-deficient livers also exhibited enhanced mitochondrial oxidative capacity. We also found that Plin5 deficiency induces lipotoxic injury in hepatocytes, attributed to lipid peroxidation. Mechanistically, we found that Plin5 blocks adipose triglyceride lipase (ATGL)-mediated lipolysis by competitively binding to comparative gene identification-58 (CGI-58) and disrupting the interaction between CGI-58 and ATGL. CONCLUSION: Plin5 is an important protective factor against hepatic lipotoxicity induced by NEFAs generated from lipolysis. This provides an important new insight into the regulation of hepatic lipid storage and relation between lipid storage and lipotoxicity.

Extracellular vesicles in breast cancer drug resistance and their clinical application.

Drug resistance currently represents a daunting challenge in the treatment of breast cancer patients. With an increased understanding of the underlying mechanisms of drug resistance, the role of extracellular vesicles (EVs) in the development of chemo-insensitivity attracts extensive attention. EVs are membrane-limited, cell type-dependent vesicles that are secreted by normal or malignant cells. EVs comprise various types of contents, including genetic cargoes, proteins, and specific lipids. The characteristics of the contents determine their specific functions in not only physiological but also pathological conditions. It has been demonstrated that miRNAs and proteins in EVs are strongly correlated with breast cancer drug resistance. Additionally, they may exert an influence on de novo and acquired resistance bioprocesses. With the advances in extraction and detection technologies, EVs have also been employed to precisely diagnose and predict the outcome of therapy in breast cancer. On the other hand, they can also be exploited as efficient delivery system in future anticancer applications. In this paper, we summarized relative mechanisms concerning the relationship between EVs and breast cancer drug resistance, and then, we provide up-to-date research advances in the clinical application of EVs.

The benign mimickers of prostatic acinar adenocarcinoma.

As the most frequent malignant histological subtype in prostatic cancer, prostatic acinar adenocarcinoma (PAA) has a series of benign mimickers including prostatic or non-prostatic lesions and normal structures, which may lead to an erroneous diagnosis and inappropriate treatment. It is very important to be aware of the existence of these mimickers and to recognize their histological features. The differential diagnosis should be based on a comprehensive evaluation of clinical history, histological structure, cytological morphology and the results of immunohistochemistry (IHC) staining, rather than on single criteria (e.g., the presence of prominent nucleoli or basal cell layer).

Probiotics Influence Gut Microbiota and Tumor Immune Microenvironment to Enhance Anti-Tumor Efficacy of Doxorubicin.

Probiotics have been reported to influence the gut microbiota and immune system in various diseases. Now, the potential impacts of probiotics on tumor treatment still need to be investigated. In this study, three strains of probiotics, Bifidobacterium breve BBr60 (BBr60), Pediococcus pentosaceus PP06 (PP06), and Bifidobacterium longum subsp. longum BL21 (BL21) were investigated for their combination with chemotherapeutic drugs doxorubicin (DOX). Our study showed that PP06 and BL21 have good performance in gastric acid, bile salt, and intestinal fluid tolerance, antimicrobial activity to pathogenic Staphylococcus aureus, and adhesion to Caco-2 cells. Besides, the probiotics all exhibited antioxidant effect, especially BL21. In vitro cytotoxicity and in vivo animal studies revealed that probiotics used alone could not directly induce anti-tumor effects, but the combination of PP06/BL21 and DOX exhibits a higher inhibition rate than DOX alone, via recruitment and infiltration of immune cells in the tumor region. After 16S rRNA analysis of fecal samples from animal models, it was found that BL21 could increase the abundance of Akkermansia, which may also play a role in regulating the tumor microenvironment to improve immune response. In conclusion, BL21 and PP06 in this study could enhance the anti-tumor efficacy by influencing the gut microbiota and tumor immune microenvironment.

Fabrication of hyaluronic acid-inulin coated Enterococcus faecium for colon-targeted delivery to fight Fusobacterium nucleatum.

The abundance of Fusobacterium nucleatum (F. nucleatum) is highly associated with the development and poor prognosis of colorectal cancer (CRC), which is regarded as a promising target for CRC. However, until now, the novel strategy to clear F. nucleatum in the colon and CRC has not been well proposed. Herein, a probiotic strain Enterococcus faecium (E. faecium, EF47) is verified to secrete various organic acids and bacteriocins to exert superior antimicrobial activity towards F. nucleatum. However, the oral delivery of EF47 is affected by the complex digestive tract environment, so we design the hyaluronic acid-inulin (HA-IN) coated EF47 for colon-targeted delivery to fight F. nucleatum. IN can protect EF47 from the harsh gastrointestinal tract environment and is degraded specifically in the colon, acting as prebiotics to further promote the proliferation of EF47. The exposed HA can also enhance the targeting effect to the tumor area via the interaction with the CD44 receptor on the tumor cells, which is confirmed to increase the adhesive ability in tumor tissues and inhibit the growth of F. nucleatum. Therefore, this colon-targeted delivery system provides a novel platform to realize high-activity and adhesive delivery of probiotics to assist the therapeutic efficiency of CRC.

Inhibition of Na+/H+ exchanger 1 by cariporide alleviates burn-induced multiple organ injury.

BACKGROUND: Severe burns initiate an inflammatory response characterized by the upregulation of proinflammatory cytokine, which contributes to multiple organ injury. Na(+)/H(+) exchanger 1 (NHE1) plays a significant role in several inflammatory processes. This study was designed to investigate the role of NHE1 in burn-induced inflammation and multiple organ injury. MATERIALS AND METHODS: Rats were subjected to a 30% total body surface area full-thickness burn. Cariporide was used to assess the function of NHE1 in burn-induced multiple organ injury by biochemical parameters, histologic changes, and inflammatory cytokine production. RESULTS: We found that NHE1 expression was significantly increased after burn injury. Inhibition of NHE1 by cariporide attenuated burn-induced edema and tissue injury in heart, lung, kidney, and small intestine. Cariporide also inhibited plasma levels of tumor necrosis factor α, interleukin 6, and myeloperoxidase activity. CONCLUSIONS: These results indicate that NHE1 inhibition prevents burn-induced multiple organ injury. The salutary effects afforded by NHE1 inhibition, at least in part, are mediated by attenuating systemic inflammatory response.

[Quantitative detection of APC/RASSF1A promoter methylation in the plasma of patients with cervical diseases].

OBJECTIVE: To quantitatively detect adenomatous polyposis coli(APC) and Ras association domain family 1A( RASSF1A) promoter methylation levels in the plasma of patients with cervical disease and to determine the diagnostic value of the indicators of cervical disease. METHODS: Preoperative blood samples were collected from 25 cases of healthy women and 118 cases of cervical disease, and tissue samples were also collected from 31 cases of them. The APC/RASSF1A promoter methylation levels of plasma and tissue were determined by duplex real-time quantitative methylation specific PCR (qMSP). RESULTS: Among 31 paired plasma and tissue samples, true negative rate of APC and RASSF1A genes were all 100%, and true positive rate of APC and RASSF1A genes were 3/5 and 7/9, respectively. In 143 cases of plasma samples, total positive rate of APC and (or) RASSF1A methylation was 3% (2/59) for control/low-grade lesions groups and 48% (40/84) for high-grade lesions/tumor groups (P < 0.01) . RASSF1A methylation rate was related to lymph node metastasis and International Federation of Gynecology and Obstetrics (FIGO) stage (P < 0.05). CONCLUSION: The plasma APC/RASSF1A methylation detection may be with some application prospect in the diagnosis of cervical diseases.

Prediction of prokaryotic and eukaryotic promoters based on information-theoretic features.

Promoters are DNA regulatory elements located near the transcription start site and are responsible for regulating the transcription of genes. DNA fragments arranged in a certain order form specific functional regions with different information contents. Information theory is the science that studies the extraction, measurement and transmission of information. The genetic information contained in DNA follows the general laws of information storage. Therefore, method in information theory can be used for the analysis of promoters carrying genetic information. In this study, we introduced the concept of information theory to the study of promoter prediction. We used 107 features extracted based on information theory methods and a backpropagation neural network to build a classifier. Then, the trained classifier was applied to predict the promoters of 6 organisms. The average AUCs of the 6 organisms obtained by using hold-out validation and ten-fold cross-validation were 0.885 and 0.886, respectively. The results verified the effectiveness of information-theoretic features in promoter prediction. Considering the possible redundancy in the feature set, we performed feature selection and obtained key feature subsets related to promoter characteristics. The results indicate the potential utility of information-theoretic features in promoter prediction.

Clinical data analysis of 86 patients with invasive infections caused by Malassezia furfur from a tertiary medical center and 37 studies.

Objective: Malassezia furfur (M. furfur) is a lipophilic, conditionally pathogenic yeast that mainly causes skin infections, but the reports of related invasive infections are increasing. The aim of this study is to provide clinical data to assist physicians in the management of patients with invasive infections caused by M. furfur. Methods: A case of pulmonary infection caused by M. furfur in a hematopoietic stem cell transplant patient for aplastic anemia was reported. In addition, the literature on invasive infection by M. furfur published in PubMed and Web of Science in English until 31 July 2022 was reviewed. Results: Clinical data analysis of 86 patients (from 37 studies and our case) revealed that most of them were preterm (44.2%), followed by adults (31.4%). M. furfur fungemia occurred in 79.1% of the 86 patients, and 45 of them were clearly obtained from catheter blood. Other patients developed catheter-related infections, pneumonia, peripheral thromboembolism, endocarditis, meningitis, peritonitis and disseminated infections. Thirty-eight preterm infants had underlying diseases such as very low birth weight and/or multiple organ hypoplasia. The remaining patients had compromised immunity or severe gastrointestinal diseases. 97.7% of patients underwent invasive procedures and 80.2% received total parenteral nutrition (TPN). Fever, thrombocytopenia and leukocytosis accounted for 55.8%, 38.4% and 24.4% of patients with M. furfur invasive infections, respectively. 69.8% of the patients received antifungal therapy, mainly amphotericin B (AmB) or azoles. Of 84 patients with indwelling catheters, 58.3% underwent the removal of catheters. TPN were discontinued in 30 of 69 patients. The all-cause mortality of 86 patients was 27.9%. Conclusions: M. furfur can cause a variety of invasive infections. These patients mostly occur in premature infants, low immunity and severe gastrointestinal diseases. Indwelling catheters and TPN infusion are major risk factors. AmB, l-AmB and azoles are the most commonly used agents, and simultaneous removal of the catheter and termination of TPN infusion are important for the treatment of M. furfur invasive infections.

Perilipin 5 deficiency aggravates cardiac hypertrophy by stimulating lactate production in leptin-deficient mice.

BACKGROUND: Perilipin 5 (Plin5) is well known to maintain the stability of intracellular lipid droplets (LDs) and regulate fatty acid metabolism in oxidative tissues. It is highly expressed in the heart, but its roles have yet to be fully elucidated. METHODS: Plin5-deficient mice and Plin5/leptin-double-knockout mice were produced, and their histological structures and myocardial functions were observed. Critical proteins related to fatty acid and glucose metabolism were measured in heart tissues, neonatal mouse cardiomyocytes and Plin5-overexpressing H9C2 cells. 2-NBDG was employed to detect glucose uptake. The mitochondria and lipid contents were observed by MitoTracker and BODIPY 493/503 staining in neonatal mouse cardiomyocytes. RESULTS: Plin5 deficiency impaired glucose utilization and caused insulin resistance in mouse cardiomyocytes, particularly in the presence of fatty acids (FAs). Additionally, Plin5 deficiency increased the NADH content and elevated the expression of lactate dehydrogenase (LDHA) in cardiomyocytes, which resulted in increased lactate production. Moreover, when fatty acid oxidation was blocked by etomoxir or LDHA was inhibited by GSK2837808A in Plin5-deficient cardiomyocytes, glucose utilization was improved. Leptin-deficient mice exhibited myocardial hypertrophy, insulin resistance and altered substrate utilization, and Plin5 deficiency exacerbated myocardial hypertrophy in leptin-deficient mice. CONCLUSION: Our results demonstrated that Plin5 plays a critical role in coordinating fatty acid and glucose oxidation in cardiomyocytes, providing a potential target for the treatment of metabolic disorders in the heart.

Resveratrol prevents hepatic steatosis induced by hepatitis C virus core protein.

Hepatitis C virus (HCV) core protein plays an important role in the development of hepatic steatosis in patients with chronic HCV infection. Treatment of C57BL/6 mice infected with HCV core recombinant adenoviruses with resveratrol significantly decreased hepatic triacylglycerols (TAG) while the serum TAG level was unaffected. RT-PCR and Western blotting showed that HCV core protein attenuated the expression of Sirt1 and PPAR-α, which would be reversed by resveratrol. This was also confirmed in primary mouse hepatic cells infected with HCV core protein expressing adenovirus. Thus, resveratrol may prevent against hepatic steatosis by blocking the inhibited expression of Sirt1 and PPAR-α induced by HCV core protein.

Septic Shock, Renal Abscess, and Bacteremia Due to Peptoniphilus asaccharolyticus in a Woman with Nephrosis and Diabetes Mellitus: Case Report and Literature Review.

Peptoniphilus asaccharolyticus is a Gram-positive anaerobic coccus, which forms part of the normal flora and the human commensals of the skin, genitourinary system, and gut. It can cause opportunistic infections in immunocompromised patients and is frequently isolated as part of polymicrobial spectra. Severe monomicrobial infections caused by the genus rarely occur. In this study, we report on septic shock, renal abscess, and bacteremia due to P. asaccharolyticus in a woman with nephrosis and diabetes mellitus. To the best of our knowledge, this report is the first to describe P. asaccharolyticus isolated from both renal abscess and blood cultures purely. The underlying diseases of the host and the removal of the double J tube were significant predisposing factors in this infection.