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As a key factor in determining testis size and sperm number, sertoli cells (SCs) play a crucial role in male infertility. Heat stress (HS) reduces SCs counts, negatively impacting nutrient transport and supply to germ cells, and leading to spermatogenesis failure in humans and animals. However, how HS affects the number of SCs remains unclear. We hypothesized that changes in SC metabolism contribute to the adverse effects of HS. In this study, we first observed an upregulation of arachidonic acid (AA), an unsaturated fatty acid after HS exposure by LC-MS/MS metabolome detection. By increasing ROS levels, expression of KEAP1 and NRF2 proteins as well as LC3 and LAMP2, 100 µM AA induced autophagy in SCs by activating oxidative stress (OS). We observed adverse effects of AA on mitochondria under HS with a decrease of mitochondrial number and an increase of mitochondrial membrane potential (MMP). We also found that AA alternated the oxygen transport and absorption function of mitochondria by increasing glycolysis flux and decreasing oxygen consumption rate as well as the expression of mitochondrial electron transport chain (ETC) proteins Complex I, II, V. However, pretreatment with 5 mM NAC (ROS inhibitor) and 2 µM Rotenone (mitochondrial ETC inhibitor) reversed the autophagy induced by AA. In summary, AA modulates autophagy in SCs during HS by disrupting mitochondrial ETC function, inferring that the release of AA is a switch-like response, and providing insight into the underlying mechanism of high temperatures causing male infertility. [ABSTRACT FROM AUTHOR]

Ganoderma meroterpenoids (GMs) containing 688 structures to date were discovered to have multiple remarkable biological activities. 65.6% of meroterpenoids featuring stereogenic centers from Ganoderma species are racemates. Further, GMs from different Ganoderma species seem to have their own characteristics. In this review, a comprehensive summarization of GMs since 2000 is presented, including GM structures, structure corrections, biological activities, physicochemical properties, total synthesis, and proposed biosynthetic pathways. Additionally, we especially discuss the racemic nature, species‐related structural distribution, and structure–activity relationship of GMs, which will provide a likely in‐house database and shed light on future studies on GMs. [ABSTRACT FROM AUTHOR]

BACKGROUND: Controlling bacterial infections in plants is a major challenge owing to the appearance of resistant strains. As a physical barrier, the bacterial biofilm helps bacterial infections acquire drug resistance by enabling bacteria to accommodate complex and volatile environmental conditions and avoid bactericidal effects. Thus, developing new antibacterial agents with antibiofilm potency is imperative. RESULTS: A series of simple triclosan derivatives containing isopropanolamine moiety were elaborately designed and assessed for their antibacterial behavior. Bioassay results showed that some title compounds had excellent bioactivity against three destructive bacteria Xanthomonas oryzae pv. oryzae (Xoo), Xanthomonas axonopodis pv. citri (Xac) and Pseudomonas syringae pv. actinidiae (Psa). Notably, compound C8 displayed high bioactivities toward Xoo and Xac, with EC50 values were 0.34 and 2.11 μg mL−1, respectively. In vivo trials revealed that compound C8 exhibited excellent protective activities against rice bacterial blight and citrus bacterial canker at 200 μg mL−1, with control effectivenesses of 49.57% and 85.60%, respectively. Compound A4 had remarkably inhibitory activity toward Psa, with an EC50 value of 2.63 μg mL−1, and demonstrated outstanding protective activity with a value of 77.23% against Psa in vivo. Antibacterial mechanisms indicated that compound C8 dose‐dependently prevented biofilm formation and extracellular polysaccharide production. C8 also significantly weakened the motility and pathogenicity of Xoo. CONCLUSION: This study contributes to the development and excavation of novel bactericidal candidates with broad‐spectrum antibacterial activity by targeting bacterial biofilm to control refractory plant bacterial diseases. © 2023 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Japanese quail (Coturnix coturnix japonica) reach sexual maturity earlier, breed rapidly and successfully, and cost less and require less space than other birds raised commercially. Given the value of this species for food production and experimental use, more studies are necessary to determine chromosomal regions and genes associated with gender and breed-differentiation. This study employed Trinity and edgeR for transcriptome analysis of next-generation RNA-seq data, which included 4 tissues obtained from 3 different breeding lines of Japanese quail (random bred control, heavy weight, low weight). Differentially expressed genes shared between female and male tissue contrast groups were analyzed to identify genes related to sexual dimorphism as well as potential novel candidate genes for molecular sexing. Several of the genes identified in the present study as significant sex-related genes have been previously found in avian gene expression analyses (NIPBL, UBAP2), and other genes found differentially expressed in this study and not previously associated with sex-related differences may be considered potential candidates for molecular sexing (TERA, MYP0, PPR17, CASQ2). Additionally, other genes likely associated with neuronal and brain development (CHKA, NYAP), as well as body development and size differentiation (ANKRD26, GRP87) in quail were identified. Expression of homeobox protein regulating genes (HXC4, ISL1) shared between our two sex-related contrast groups (Female Brain vs. Male Brain and Ovary vs. Testis) indicates that these genes may regulate sex-specific anatomical development. Results reveal genetic features of the quail breed and could allow for more effective molecular sexing as well as selective breeding for traits important in commercial production.

Sertoli cells (SCs) provide structural and nutritional support for developing germ cells. Normal glucose metabolism of SCs is necessary for spermatogenesis. Melatonin could alleviate the effects of heat stress on spermatogenesis. However, the influences of heat stress on glucose metabolism in SCs remain unclear, and the potential protective mechanisms of melatonin on SCs need more exploration. In this study, boar SCs were treated at 43°C for 30 min, and different concentrations of melatonin were added to protect SCs from heat stress‐induced impairment. These results showed that heat stress‐induced oxidative stress caused cell apoptosis, inhibited the pentose phosphate pathway, and decreased the ATP content. Furthermore, heat stress increased the expressions of glucose intake‐ and glycolytic‐related enzymes, which enhanced the glycolysis activity to compensate for the energy deficit. Melatonin relieved heat stress‐induced oxidative stress and apoptosis by activating the Kelch‐like ECH‐associated protein 1 (KEAP1)/NF‐E2‐related factor 2 signaling pathway to increase the capacity of antioxidants. In addition, melatonin enhanced heat‐shock protein 90 (HSP90) expression through melatonin receptor 1B (MTNR1B), thereby stabilizing hypoxia‐inducible factor‐1α (HIF‐1α). Activation of the HIF‐1α signaling pathway enhanced glycolysis, promoted the pentose phosphate pathway, and increased cell viability. Our results suggest that melatonin reprograms glucose metabolism in SCs through the MTNR1B–HSP90–HIF‐1α axis and provides a theoretical basis for preventing heat stress injury. [ABSTRACT FROM AUTHOR]

Two new mertoterpenoids, australins A (1) and B (2), and a new alkaloid, australine (4), together with five known compounds (3, 5–8) were isolated from the fruiting bodies of Ganoderma australe. Their structures including absolute configurations were assigned by using spectroscopic methods and electronic circular dichroism (ECD) calculations. Racemic australin A was further purified by chiral HPLC. Biological assessments reveal that compounds (+)-1 and 7 could significantly protect SH-SY5Y cells from glutamate-induced neural excitotoxicity. [ABSTRACT FROM AUTHOR]

Obstructive nephropathy is the end result of a variety of diseases that block drainage from the kidney(s). Transforming growth factor‐β1 (TGF‐β1)/Smad3‐driven renal fibrosis is the common pathogenesis of obstructive nephropathy. In this study, we identified petchiether A (petA), a novel small‐molecule meroterpenoid from Ganoderma, as a potential inhibitor of TGF‐β1‐induced Smad3 phosphorylation. The obstructive nephropathy was induced by unilateral ureteral obstruction (UUO) in mice. Mice received an intraperitoneal injection of petA/vehicle before and after UUO or sham operation. An in vivo study revealed that petA protected against renal inflammation and fibrosis by reducing the infiltration of macrophages, inhibiting the expression of proinflammatory cytokines (interleukin‐1β and tumour necrosis factor‐α) and reducing extracellular matrix deposition (α‐smooth muscle actin, collagen I and fibronectin) in the obstructed kidney of UUO mice; these changes were associated with suppression of Smad3 and NF‐κB p65 phosphorylation. Petchiether A inhibited Smad3 phosphorylation in vitro and down‐regulated the expression of the fibrotic marker collagen I in TGF‐β1‐treated renal epithelial cells. Further, we found that petA dose‐dependently suppressed Smad3‐responsive promoter activity, indicating that petA inhibits gene expression downstream of the TGF‐β/Smad3 signalling pathway. In conclusion, our findings suggest that petA protects against renal inflammation and fibrosis by selectively inhibiting TGF‐β/Smad3 signalling. [ABSTRACT FROM AUTHOR]

Six new meroterpenoids, australeols A−F (1 – 6), together with nineteen known compounds (7 – 25), were isolated from the fruiting bodies of Ganoderma australe. Their structures including absolute configurations were assigned by using spectroscopic methods, CD comparison, and X-ray crystallography analysis. Biological evaluation reveals that compounds 13 , (–)- 19 , and 23 exhibit potent neuroprotective activities in glutamate-stimulated SH-SY5Y cells. Unlabelled Image [ABSTRACT FROM AUTHOR]

Pancreatic cancer has a poor survival rate as compared to other types of cancer. Surface marker CD44 plays important role in epithelial-mesenchymal transition and cancer stem cell phenotype. Therefore, targeting CD44 positive pancreatic cancer cells might enhance therapies effectiveness. Our previous studies indicated the antitumorigenesis effect of BRM270 in osteosarcoma, lung cancer, and glioblastoma; however there is no evidence on BRM270 impacts on pancreatic cancer growth. In this study, we investigated the effect of BRM270 on the isolated CD44 positive pancreatic ductal adenocarcinoma cells (CD44+ PDAC). Results showed that CD44 positive cells undergo apoptosis induced by BRM270. Moreover, BRM270 also inhibits stemness and metastasis traits in CD44+ PDAC via Sonic hedgehog signaling pathway and SALL4 expression. In vivo study indicated that tumor growth derived from CD44+ PDAC was suppressed as daily uptake by BRM270 5 mg/kg. These data suggest the alternative approach in antipancreatic tumorigenesis via herbal plants extract and selectively targeting CD44+ PDAC cells in tumor. [ABSTRACT FROM AUTHOR]

Abstract Pancreatic ductal adenocarcinoma (PDAC) is a major malignant phenotype in pancreatic cancer, which is one of the most death causes by cancer in the world. PDAC developed from pancreatic intra-epithelial neoplasms (PanINs) and poorly diagnosed at early stages. Beside of high drug resistance, metastasis is the great concern during pancreatic cancer treatment. SALL4 expression is inherent in the upregulations of endothelial mesenchymal transition (EMT) genes and therefore promoting cancer metastasis. Furthermore, some of evidences indicated reactive oxygen species (ROS) is also influent to metastasis and self-antioxidant capacity seems a gold standard for successful metastasis rate. In this study, we have found the role Spalt like protein 4 (SALL4) to PDAC proliferation, mobility and its regulation to mitochondrial ROS via FoxM1/Prx III axis. It is possible that SALL4 mainly induces endothelial-mesenchymal transition (EMT) phenotype and favors ROS loss to facilitate metastasis efficiency in PDAC cells. Therefore, SALL4 might be a promising marker for PDAC treatment and targeting SALL4 would benefit anti-proliferative and anti-metastasis therapies. Highlights • SALL4 promotes stemness traits and metastatic phenotype in vitro. • SALL4 expression positively impacts PDAC-derived tumor growth. • SALL4 regulates intracellular ROS via FoxM1/Prx III by activation of ERK1/2. [ABSTRACT FROM AUTHOR]

Inflammation is tightly associated with carcinogenesis at both the initiation and development of tumor. Many reports indicated that Cox-2 substantially contributes to inflammation and tumorigenesis. The novel nutraceutical KJS018A (BRM270 Function Enhanced Products) is the extract mixture from 8 herbal plants, which have been used to inhibit cancers and inflammation. The aim of the present study is to examine the inhibitory effects of KJS018A mixture to hepatocarcinogenesis and inflammation. The results showed that KJS018A significantly inhibited the proliferation of hepatic malignant cells and downregulated levels of IL-6 and Cox-2. Furthermore, KJS018A diminished the effect of PMA, an inflammatory inducer via IL-6/STAT3/Cox-2 pathway. Furthermore, KJS018A suppressed metastatic traits of hepatic malignant cells via downregulating Twist, N-cadherin, and MMP-9 while restoring E-cadherin expression. KJS018A also restrained tumor growth and levels of IL-6 and Cox-2 in immunohistochemistry staining. Taken together, these data suggest potential application of KJS018A in prevention of hepatocarcinogenesis promoted by inflammation. [ABSTRACT FROM AUTHOR]

Ganoderpetchoids A−E and (−)-dayaolingzhiol H, six undescribed meroterpenoids, were isolated from Ganoderma petchii. Their structures including the relative configurations were identified by means of spectroscopic methods and 13C NMR calculations. Chiral separation of the new racemics was performed to afford their respective enantiomers. The absolute configurations of the new isolates were clarified by computational approaches, CD comparisons and X-ray diffraction analysis. Biological studies toward triple negative breast cancer indicated that (+)- 6 and (−)- 6 significantly inhibit the migration of MDA-MB-231 cell line. [Display omitted] [ABSTRACT FROM AUTHOR]

Chronic excessive alcohol consumption (more than 40–80 g/day for males and more than 20–40 g/day for females) could induce serious liver injury. In this study, effects of lemon juice on chronic alcohol-induced liver injury in mice were evaluated. The serum biochemical profiles and hepatic lipid peroxidation levels, triacylglycerol (TG) contents, antioxidant enzyme activities, and histopathological changes were examined for evaluating the hepatoprotective effects of lemon juice in mice. In addition, the in vitro antioxidant capacities of lemon juice were determined. The results showed that lemon juice significantly inhibited alcohol-induced increase of alanine transaminase (ALT), aspartate transaminase (AST), hepatic TG, and lipid peroxidation levels in a dose-dependent manner. Histopathological changes induced by alcohol were also remarkably improved by lemon juice treatment. These findings suggest that lemon juice has protective effects on alcohol-induced liver injury in mice. The protective effects might be related to the antioxidant capacity of lemon juice because lemon juice showed in vitro antioxidant capacity. [ABSTRACT FROM AUTHOR]

Many mushrooms have been used as foods and medicines for a long time. Mushrooms contain polyphenols, polysaccharides, vitamins and minerals. Studies show that mushrooms possess various bioactivities, such as antioxidant, anti-inflammatory, anticancer, immunomodulatory, antimicrobial, hepatoprotective, and antidiabetic properties, therefore, mushrooms have attracted increasing attention in recent years, and could be developed into functional food or medicines for prevention and treatment of several chronic diseases, such as cancer, cardiovascular diseases, diabetes mellitus and neurodegenerative diseases. The present review summarizes the bioactivities and health benefits of mushrooms, and could be useful for full utilization of mushrooms. [ABSTRACT FROM AUTHOR]