The Dynamic Change of Gene-Regulated Networks in Cashmere Goat Skin with Seasonal Variation.

The Cashmere goat (Capra hircus) is renowned for its high-quality fiber production trait. The hair cycle in Cashmere goat has an annual rhythm. To deepen the understanding of the molecular foundation of annual rhythm in the skin of Cashmere goat, we did a comparative analysis of the Cashmere goat skin transcriptome all year round. 4002 Differentially expressed genes (DEGs) were identified with seasonal variations. 12 months transcriptome were divided into four developmental stages: Jan-Mar, Apr-Jul, Aug-Oct, and Nov-Dec based on gene expression patterns. 13 modules of highly correlated genes in skin were identified using WGCNA. Ten of these modules were consistent with the development stages. The gene function of those genes in each module was analyzed by functional enrichment. The results indicated that Wnt and Hedgehog signaling pathways were inhibited from January to March and activated from April to July. The cutaneous immune system of Cashmere goats has high activity from August to October. Fatty acid metabolism dominates goat skin from November to December. This study provides new information related to the annual skin development cycle, which could provide molecular biological significance for understanding the seasonal development and response to the annual rhythm of skin.

Fufang Zhenzhu Tiaozhi (FTZ) capsule ameliorates diabetic kidney disease in mice via inhibiting the SGLT2/glycolysis pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Fufang Zhenzhu Tiaozhi (FTZ) capsule is a hospital preparation of a patented traditional Chinese medicine compound. FTZ has been clinically used for nearly 13 years in the treatment of diabetes and glycolipid metabolic diseases. With the significant benefits of SGLT2 inhibitor in patients with diabetic kidney disease (DKD), it provides a research avenue to explore the mechanism of FTZ in treating this disease based on glycolysis pathway. AIM OF THE STUDY: To explore the pharmacological characteristics of FTZ in DKD mice and its impact on the glycolysis pathway. MATERIALS AND METHODS: We induced a DKD model in C57BL/6 mice by injection of streptozotocin (STZ) combined with long-term high-fat diet. We administered three doses of FTZ for 12 weeks of treatment. Kidney function, blood lipid levels, glucose tolerance, and key glycolytic enzymes were evaluated. Renal pathological changes were observed using HE, MASSON, and PAS staining. The potential targets of the active ingredients of FTZ in the glycolysis pathway were predicted using network pharmacology and molecular docking. Validation was performed using immunohistochemistry and Western blotting. RESULTS: FTZ effectively reduces blood glucose, total cholesterol, triglyceride, low density lipoprotein cholesterol, 24 h proteinuria, serum creatinine, blood urea nitrogen, and increases urinary glucose levels. Glucose tolerance and renal pathological changes were significantly improved by FTZ treatment. Pinusolidic acid, a component of FTZ, shows good binding affinity with three active pockets of SGLT2. WB and immunohistochemistry revealed that FTZ significantly inhibits the expression of SGLT2 and its glycolytic related proteins (GLUT2/PKM2/HK2). Hexokinase, pyruvate kinase, and lactate dehydrogenase in the kidney were also significantly inhibited by FTZ in a dose-dependent manner. CONCLUSION: FTZ may alleviate the progression of DKD by inhibiting the activation of the SGLT2/glycolytic pathway. Our study provides new insights into the clinical application of FTZ in DKD.

Th17 cells: A new target in kidney disease research.

Type 17 T helper (Th17) cells, which are a subtype of CD4+ T helper cells, secrete pro-inflammatory cytokines such as IL-17A, IL-17F, IL-21, IL-22, and GM-CSF, which play crucial roles in immune defence and protection against fungal and extracellular pathogen invasion. However, dysfunction of Th17 cell immunity mediates inflammatory responses and exacerbates tissue damage. This pathological process initiated by Th17 cells is common in kidney diseases associated with renal injury, such as glomerulonephritis, lupus nephritis, IgA nephropathy, hypertensive nephropathy, diabetic kidney disease and acute kidney injury. Therefore, targeting Th17 cells to treat kidney diseases has been a hot topic in recent years. This article reviews the mechanisms of Th17 cell-mediated inflammation and autoimmune responses in kidney diseases and discusses the related clinical drugs that modulate Th17 cell fate in kidney disease treatment.

IL-17 and IL-17-producing cells (mainly Th17 cells) are crucial for kidney diseases. Multiple factors and mechanisms are involved in Th17 cell polarization, including oxidative stress, abnormal glucolipid metabolism, miRNA dysfunction, and microbial metabolism. This pathological process initiated by Th17 cells is common in kidney diseases associated with renal injury, such as glomerulonephritis, lupus nephritis, IgA nephropathy, hypertensive nephropathy, diabetic kidney disease and acute kidney injury. Modulating the direction of Th17 cell differentiation is a highly attractive therapeutic approach. This article reviews the mechanisms of Th17 cell-mediated inflammation and autoimmune responses in kidney diseases and discusses the related clinical drugs that modulate Th17 cell fate in kidney disease treatment.

Comparative and phylogenetic analysis of the complete chloroplast genome sequences of Allium mongolicum.

Allium mongolicum Regel is a wild and sandy vegetable with unique flavours. In this study, a complete chloroplast (cp) genome of A. mongolicum was obtained (Genbank accession number: OM630416), and contained 153,609 base pairs with the GC ratio as 36.8%. 130 genes were annotated including 84 protein-coding genes, 38 tRNA, and 8 rRNA genes. The large single-copy (LSC) region was 82,644 bp, and a small single-copy (SSC) region was 18,049 bp, which were separated by two inverted repeats (IRs, including IRa and IRb) of 26,458 bp. Comparative genome analyses of 55 Allium species suggested that genomic structure of genus Allium was conserved, and LSC and SSC regions were outstanding with high variability. Among them, more divergent loci were in the SSC region covering ycf1-rrn4.5 and ndhF-ccsA. Phylogenetic analysis on cp genomes of 55 Allium determined that all members were clustered into 13 clades, and A. mongolicum had close relationship with A. senescens. Corresponding analyses of four protein-coding genes (ycf1, ndhF, rpl32, and ccsA) in aforementioned divergent loci confirmed that ycf1 was finally chosen as the candidate gene for species identification and evolutionary classification of genus Allium. These data provide valuable genetic resources for future research on Allium.

Trefoil factor 3: New highlights in chronic kidney disease research.

Trefoil factor 3 (TFF3, also known as intestinal trefoil factor) is a small-molecule peptide containing a typical trefoil structure. TFF3 has several biological effects, such as wound healing, immune regulation, neuroprotection, and cell migration and proliferation promotion. Although TFF3 binding sites were identified in rat kidneys more than a decade ago, the specific effects of this small-molecule peptide on kidneys remain unclear. Until recently, much of the research on TFF3 in the kidney field has focused exclusively on its role as a biomarker. Notably, a large prospective randomized study of patients with 29 common clinical diseases revealed that chronic kidney disease (CKD) was associated with the highest serum TFF3 levels, which were 3-fold higher than in acute gastroenteritis, which had the second-highest levels. Examination of each stage of CKD revealed that urine and serum TFF3 levels significantly increased with the progression of CKD. These results suggest that the role of TFF3 in CKD needs further research. The present review summarizes the renal physiological expression, biological functions, and downstream signaling of TFF3, as well as the upstream events that lead to high expression of TFF3 in CKD.

Hirsutanol A exhibits neuroprotective activities against sevoflurane-induced neurotoxicity in aged rats.

The neurotoxicity of the inhaled anesthetic, sevoflurane, has been documented in a number of studies. In this study, we conducted experiments to investigate whether Hirsutanol A (HA), a sesquiterpene compound from the fungus, Chondrostereum sp., can provide protection from sevoflurane-induced neurological toxicity in aged rats, and analyzed the underlying mechanisms. The cognitive dysfunction of rats following sevoflurane exposure was evaluated by behavioral tests. The neuronal cell survival was determined by Nissl staining. In addition, human neuroblastoma H4 cells were exposed to sevoflurane to establish an in vitro model. Apoptotic marker expression in hippocampal tissue was determined by western blotting. Cell apoptosis in vitro was also examined by TUNEL assay and flow cytometry. The expression and translocation of Nrf2 were examined by both western blot and immunofluorescence staining. Our results show that HA significantly attenuated sevoflurane-induced cognitive impairment in aged rats. In addition, HA treatment decreased sevoflurane-induced neuronal apoptosis in the hippocampus and alleviated Aß accumulation. Our results also show that the neuroprotective effect of HA is associated with the activation of Nrf2 signaling. Human neuroblastoma H4 cells were used as a model to examine the protective activity of HA against sevoflurane-induced neurotoxicity. In addition, our results show that the inhibition of Nrf2 by a specific inhibitor or targeting siRNA significantly compromises the attenuating effect of HA on sevoflurane-induced cell apoptosis and Aß accumulation. Our results suggest that HA may function as a neuroprotective agent against sevoflurane-induced neurotoxicity.

Identification of Glutathione Peroxidase Gene Family in Ricinus communis and Functional Characterization of RcGPX4 in Cold Tolerance.

Glutathione peroxidases (GPXs) protect cells against damage caused by reactive oxygen species (ROS) and play key roles in regulating many biological processes. Here, five GPXs were identified in the Ricinus communis genome. Phylogenetic analysis displayed that the GPXs were categorized into five groups. Conserved domain and gene structure analyses showed that the GPXs from different plant species harbored four highly similar motifs and conserved exon-intron arrangement patterns, indicating that their structure and function may have been conserved during evolution. Several abiotic stresses and hormone-responsive cis-acting elements existed in the promoters of the RcGPXs. The expression profiles indicated that the RcGPXs varied substantially, and some RcGPXs were coordinately regulated under abiotic stresses. Overexpression of RcGPX4 in Arabidopsis enhanced cold tolerance at seed germination but reduced freezing tolerance at seedlings. The expression of abscisic acid (ABA) signaling genes (AtABI4 and AtABI5), ABA catabolism genes (AtCYP707A1 and AtCYP707A2), gibberellin acid (GA) catabolism gene (AtGA2ox7), and cytokinin (CTK)-inducible gene (AtARR6) was regulated in the seeds of transgenic lines under cold stress. Overexpression of RcGPX4 can disturb the hydrogen peroxide (H2O2) homeostasis through the modulation of some antioxidant enzymes and compounds involved in the GSH-ascorbate cycle in transgenic plants. Additionally, RcGPX4 depended on the MAPK3-ICE1-C-repeat-binding factor (CBF)-COR signal transduction pathway and ABA-dependent pathway to negatively regulate the freezing tolerance of transgenic plants. This study provides valuable information for understanding the potential function of RcGPXs in regulating the abiotic stress responses of castor beans.

Synthesis and properties of surface molecular imprinting adsorbent for removal of Pb(2+).

A new chitosan imprinting adsorbent using diatomite as core material was prepared by using the surface molecular imprinting technology with the Pb(2+) as imprinted ion. The preparation process conditions of the surface molecular imprinting adsorbent were studied. The adsorbent was characterized by using Fourier transform infrared (FTIR) spectrum. FTIR spectrum indicated that it was cross-linked by epichlorohydrin. The new imprinting adsorbent could provide a higher adsorption capacity for Pb(2+), which reached 139.6 mg/g increasing 32.3% compared with cross-linking chitosan adsorbent (the initial Pb(2+) concentration of 600 mg/L). The adsorption velocity was quick and the equilibration time of the imprinting adsorbent for Pb(2+) was 3 h that shortened about 40% compared with cross-linking chitosan adsorbent. It had a more wide pH range of 5-7 than that of cross-linking chitosan adsorbent. The new imprinting adsorbent can be reused for up to ten cycles without loss of adsorption capacity. In the kinetics and isotherm study, the pseudosecond order model and Langmuir model could represent the adsorption process.

[Expression of p16 and nm23 genes in salivary gland tumors].

OBJECTIVE: To study the expression of p16 and nm23 genes in salivary gland tumors and the relation of P16 and nm23 proteins with fumorigenesis of salivary gland tumors. METHODS: Expression of P16 and nm23 proteins was examined by SABC immunohistochemical method in 39 cases of paraffin blocks of normal salivary gland tissues and salivary gland tumors. RESULTS: P16 and nm23 protein positive staining were mainly found in the cytoplasm and cytoblast of all salivary gland tissues. Positive rate of P16 protein expression was 76.9% (10/13) and 40.9% (9/22) in benign and malignant salivary gland tumors, respectively. There was significant difference between P16 protein expression of benign and malignant tumors by chi 2 test (P < 0.05). mm23 protein positive staining was found in 84.6% (11/13) and 45.5% (10/22) of benign and malignant tumors respectively. The expression of nm23 protein in benign and malignant tumors was significantly different (P < 0.05). There was no correlation of the expression of P16 and nm23 in salivary gland tumors was found (P > 0.05). CONCLUSION: p16 and nm23 genes may play an important role in different sides in salivary gland tumorigenesis and the reduce of the expression of p16 and nm23 genes may contribute to the generation of malignant salivary gland tumors.