Predicting the potential distribution of Dendrolimus punctatus and its host Pinus massoniana in China under climate change conditions.

Introduction: Dendrolimus punctatus, a major pest endemic to the native Pinus massoniana forests in China, displays major outbreak characteristics and causes severe destructiveness. In the context of global climate change, this study aims to investigate the effects of climatic variations on the distribution of D. punctatus and its host, P. massoniana. Methods: We predict their potential suitable distribution areas in the future, thereby offering a theoretical basis for monitoring and controlling D. punctatus, as well as conserving P. massoniana forest resources. By utilizing existing distribution data on D. punctatus and P. massoniana, coupled with relevant climatic variables, this study employs an optimized maximum entropy (MaxEnt) model for predictions. With feature combinations set as linear and product (LP) and the regularization multiplier at 0.1, the model strikes an optimal balance between complexity and accuracy. Results: The results indicate that the primary climatic factors influencing the distribution of D. punctatus and P. massoniana include the minimum temperature of the coldest month, annual temperature range, and annual precipitation. Under the influence of climate change, the distribution areas of P. massoniana and its pests exhibit a high degree of similarity, primarily concentrated in the region south of the Qinling-Huaihe line in China. In various climate scenarios, the suitable habitat areas for these two species may expand to varying degrees, exhibiting a tendency to shift toward higher latitude regions. Particularly under the high emission scenario (SSP5-8.5), D. punctatus is projected to expand northwards at the fastest rate. Discussion: By 2050, its migration direction is expected to closely align with that of P. massoniana, indicating that the pine forests will continue to be affected by the pest. These findings provide crucial empirical references for region-specific prevention of D. punctatus infestations and for the rational utilization and management of P. massoniana resources.

Embryo Microinjection for Transgenesis in Drosophila.

Transgenesis in Drosophila is an essential approach to studying gene function at the organism level. Embryo microinjection is a crucial step for the construction of transgenic flies. Microinjection requires some types of equipment, including a microinjector, a micromanipulator, an inverted microscope, and a stereo microscope. Plasmids isolated with a plasmid miniprep kit are qualified for microinjection. Embryos at the pre-blastoderm or syncytial blastoderm stage, where nuclei share a common cytoplasm, are subjected to microinjection. A cell strainer eases the process of dechorionating embryos. The optimal time for dechorionation and desiccation of embryos needs to be determined experimentally. To increase the efficiency of embryo microinjection, needles prepared by a puller need to be beveled by a needle grinder. In the process of grinding needles, we utilize a foot air pump with a pressure gauge to avoid the capillary effect of the needle tip. We routinely inject 120-140 embryos for each plasmid and obtain at least one transgenic line for around 85% of plasmids. This article takes the phiC31 integrase-mediated transgenesis in Drosophila as an example and presents a detailed protocol for embryo microinjection for transgenesis in Drosophila.

Effects of Ellagic Acid on Glucose and Lipid Metabolism: A Systematic Review and Meta-Analysis.

Background: Abnormal glucose and lipid metabolism (GALM) serve as both a cause and an inducer for the development of the disease. Improvement and treatment of GALM are an important stage to prevent the occurrence and development of the disease. However, current clinical treatment for GALM is limited. Ellagic acid (EA), a common polyphenol present in foods, has been shown to improve abnormalities in GALM observed in patients suffering from metabolic diseases. Objective: This study used a meta-analysis method to systematically assess the effects of EA on GALM. Method: As of November 8, 2023, a comprehensive search was conducted across 5 databases, namely, PubMed, Embase, Web of Science, Cochrane Library, and Google Scholar to identify randomized controlled trials (RCTs) in which EA served as the primary intervention for diseases related to GALM. The risk of bias within the included studies was assessed according to the Cochrane Handbook. All statistical analyzes were performed using RevMan 5.4 software. Results: In this study, a total of 482 articles were retrieved, resulting in the inclusion of 10 RCTs in the meta-analysis. The results showed that EA could reduce fasting blood glucose (FBG) (p = 0.008), increase insulin secretion (p = 0.01), improve insulin resistance index (HOMA-IR) (p = 0.003), decrease triglyceride (TG) (p = 0.004), and reduce cholesterol (Chol) (p = 0.04) and low-density lipoprotein (LDL-c) (p = 0.0004). EA had no significant effect on waist circumference (WC), body weight (BW), body mass index (BMI), 2 hours after prandial blood glucose (2 h-PG), total cholesterol (TC), and high-density lipoprotein (HDL-c). Conclusions: The effect of improvement in glucose and lipids of EA was closely related to the dose and the intervention time. EA can improve GALM caused by diseases. To corroborate the findings of this study and improve the reliability of the results, EA is imperative to refine the research methodology and increase the sample size in future investigations.

Serum 25-hydroxyvitamin D concentrations, vitamin D receptor polymorphisms, and risk of infections among individuals with type 2 diabetes: a prospective cohort study.

BACKGROUND: Evidence on the association between serum 25-hydroxyvitamin D [25(OH)D] and infections among patients with type 2 diabetes (T2D), a group susceptible to vitamin D deficiency and infections, is limited. OBJECTIVES: We aimed to examine this association in individuals with T2D, and to evaluate whether genetic variants in vitamin D receptor (VDR) would modify this association. METHODS: This study included 19,851 participants with T2D from United Kingdom Biobank. Infections were identified by linkage to hospital inpatient and death registers. Negative binomial regression models were used to estimate incidence rate ratios (IRRs) and 95% confidence intervals (CIs), with adjustment of potential confounders. RESULTS: In patients with T2D, the incidence rate of infections was 29.3/1000 person-y. Compared with those with 25(OH)D of 50.0-74.9 nmol/L, the multivariable-adjusted IRRs and 95% CIs of total infections, pneumonia, gastrointestinal infections, and sepsis were 1.44 (1.31, 1.59), 1.49 (1.27, 1.75), 1.47 (1.22, 1.78), and 1.41 (1.14, 1.73), respectively, in patients with 25(OH)D <25.0 nmol/L. Nonlinear inverse associations between 25(OH)D concentrations and the risks of total infections (P-overall < 0.001; P-nonlinear = 0.002) and gastrointestinal infections (P-overall < 0.001; P-nonlinear = 0.040) were observed, with a threshold effect at ∼50.0 nmol/L. The vitamin D-infection association was not modified by genetic variants in VDR (all P-interaction > 0.050). CONCLUSIONS: In patients with T2D, lower serum 25(OH)D concentration (<50 nmol/L) was associated with higher risks of infections, regardless of genetic variants in VDR. Notably, nonlinear inverse associations between 25(OH)D concentrations and the risks of infections were found, with a threshold effect at ∼50.0 nmol/L. These findings highlighted the importance of maintaining adequate vitamin D in reducing the risk of infections in patients with T2D.

Oridonin attenuates diabetes­induced renal fibrosis via the inhibition of TXNIP/NLRP3 and NF­κB pathways by activating PPARγ in rats.

INTRODUCTION: Oridonin possesses remarkable anti-inflammatory, immunoregulatory properties. However, the renoprotective effects of Oridonin and the underlying molecular mechanisms have not been explored in Diabetic Nephropathy (DN). We hypothesized that Oridonin could ameliorate diabetes­induced renal fibrosis. METHODS: We used streptozocin (STZ)-induced diabetic rats combined high-fat diet to establish a type 2 diabetes mellitus (T2DM) animal model, and then treated with Oridonin (10,20mg/kg/day) for two weeks. Kidney function and renal fibrosis were assessed. We also treated high glucose-induced human renal proximal tubule epithelial cells (HK-2) with Oridonin. In addition, the expression of inflammatory factors and fibrotic markers were analyzed. RESULTS: Oridonin treatment preserved kidney function and markedly limited the renal fibrosis size in diabetic rats. The renal fibrotic markers were inhibited in the 10mg/kg/day group and 20mg/kg/day group compared to the T2DM group. Moreover, the expression levels of TXNIP/NLRP3 and NF­κB pathway were decreased and the level of PPARγ were increased in the Oridonin treatment group compared to non-treated group. In vitro, intervention of PPARγ could significantly regulate the effect of Oridonin on the high glucose-induced inflammatory changes in HK-2. CONCLUSION: Oridonin reduces renal fibrosis and preserves kidney function via the inhibition of TXNIP/NLRP3 and NF­κB pathway by activating PPARγ in T2DM rat model, which indicates potential therapeutic effect of Oridonin on DN.

Toxoplasma gondii suppresses proliferation and migration of breast cancer cells by regulating their transcriptome.

BACKGROUND: Breast cancer is the most common cancer in women worldwide. Toxoplasma gondii (T. gondii) has shown anticancer activity in breast cancer mouse models, and exerted beneficial effect on the survival of breast cancer patients, but the mechanism was unclear. METHODS: The effect of tachyzoites of T. gondii (RH and ME49 strains) on human breast cancer cells (MCF-7 and MDA-MB-231 cells) proliferation and migration was assessed using cell growth curve and wound healing assays. Dual RNA-seq was performed for T. gondii-infected and non-infected cells to determine the differentially expressed genes (DEGs). Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Protein-Protein Interaction Networks analysis (PPI) were performed to explore the related signaling pathway and hub genes. Hub genes were validated using the Kaplan-Meier plotter database, and Pathogen Host Interaction (PHI-base) database. The results were verified by qRT-PCR. RESULTS: The tachyzoites of T. gondii decreased the expression of Ki67 and increased the expression of E-cadherin, resulting in suppressing the proliferation and migration of infected human breast cancer cells. The inhibitory effect of T. gondii on breast cancer cells showed a significant dose-response relationship. Compared with the control group, 2321 genes were transcriptionally regulated in MCF-7 cells infected with T. gondii, while 169 genes were transcriptionally regulated in infected MDA-MB-231 cells. Among these genes, 698 genes in infected MCF-7 cells and 67 genes in infected MDA-MB-231 cells were validated by the publicly available database. GO and KEGG analyses suggested that several pathways were involved in anticancer function of T. gondii, such as ribosome, interleukin-17 signaling, coronavirus disease pathway, and breast cancer pathway. BRCA1, MYC and IL-6 were identified as the top three hub genes in infected-breast cancer cells based on the connectivity of PPI analysis. In addition, after interacting with breast cancer cells, the expression of ROP16 and ROP18 in T. gondii increased, while the expression of crt, TgIST, GRA15, GRA24 and MIC13 decreased. CONCLUSIONS: T. gondii transcriptionally regulates several signaling pathways by altering the hub genes such as BRCA1, MYC and IL-6, which can inhibit the breast tumor growth and migration, hinting at a potential therapeutic strategy.

Restraint Stress, Foot Shock and Corticosterone Differentially Alter Autophagy in the Rat Hippocampus, Basolateral Amygdala and Prefrontal Cortex.

Autophagy is a conserved lysosomal degradation process that has recently been found to be associated with stress-related psychological diseases. However, previous studies have yielded inconsistent results regarding the effects of various stress patterns on autophagy in different brain regions. This discrepancy may arise from differences in autophagy flux across nuclei, the type of stress experienced, and the timing of autophagy assessment after stress exposure. In this study, we assessed autophagy flux in the rat hippocampus (HPC), medial prefrontal cortex (mPFC), and basal lateral amygdala (BLA) by quantifying protein levels of p-ULK1, LC3-I, LC3-II, and p62 via Western blot analysis at 15 min, 30 min, and 60 min following various stress paradigms: restraint stress, foot shock, single corticosterone injection, and chronic corticosterone treatment. We found that: (1) hippocampal autophagy decreased within 1 h of restraint stress, foot shock, and corticosterone injection, except for a transient increase at 30 min after restraint stress; (2) autophagy increased 1 h after restraint stress and corticosterone injection but decreased 1 h after foot shock in mPFC; (3) In BLA, autophagy increased 1 h after foot shock and corticosterone injection but decreased 1 h after restraint stress; (4) Chronic corticosterone increased autophagy in mPFC and BLA but had no effects in HPC. These findings suggest that stress regulates autophagy in a brain region- and stressor-specific manner within 1 h after stress exposure, which may contribute to the development of stress-related psychological disorders.

Multi-frequency ultrasound-assisted cellulase extraction of protein from mulberry leaf: Kinetic, thermodynamic, and structural properties.

The effects of different extraction methods (traditional extraction, ultrasound extraction, cellulase extraction, and ultrasound-assisted cellulase extraction) on the yield of mulberry leaf protein (MLP) were investigated, and the results revealed that multi-frequency ultrasound-assisted cellulase extraction was the most efficient extraction method. The mechanism of the synergistic extraction method used to efficiently extract protein from mulberry leave was investigated, focusing on the kinetics and thermodynamics of the enzymatic process. The results revealed that kinetic parameters KM decreased by 14.07% and kA increased by 5.02%, and the thermodynamic parameters Ea, ΔH, and ΔS decreased by 44.81%, 48.41%, and 21.12 %, respectively, following the process of multi-frequency ultrasound (MFU) pretreatment. The spectral analysis with fluorescence spectra manifested that ultrasound exposed hydrophobic groups and induced molecular unfolding of MLP. Atomic force microscope showed that ultrasound decreased particle size while increasing flexibility of MLP. The effect of ultrasound increases the binding frequency of cellulase and substrates, resulting in greater affinity between the two and promoting the solubilization of MLP. This study provides a theoretical basis to improve the application prospects of MLP.

Characteristics of enzymolysis of silkworm pupa protein after tri-frequency ultrasonic pretreatment: kinetics, thermodynamics, structure and antioxidant changes.

As a by-product of the sericulture industry, the utilization rate of silkworm pupa resources is currently not high. Proteins are converted into bioactive peptides through enzymatic hydrolysis. Not only can it solve the utilization problem, but it also creates more valuable nutritional additives. Silkworm pupa protein (SPP) was pretreated with tri-frequency ultrasonic (22/28/40 kHz). Effects of ultrasonic pretreatment on enzymolysis kinetics, enzymolysis thermodynamics, hydrolysate structure as well as hydrolysate antioxidant of SPP were investigated. Ultrasonic pretreatment significantly increased the hydrolysis efficiency, showing a 6.369% decrease in k m and a 16.746% increase in k A after ultrasonic action (p < 0.05). The SPP enzymolysis reaction followed a second-order rate kinetics model. Evaluation of enzymolysis thermodynamics revealed that Ultrasonic pretreatment markedly enhanced the SPP enzymolysis, leading to a 21.943% decrease in E a. Besides, Ultrasonic pretreatment significantly increased SPP hydrolysate's surface hydrophobicity, thermal stability, crystallinity, and antioxidant activities (DPPH radical scavenging activity, Fe2+ chelation ability, and reducing power). This study indicated that tri-frequency ultrasonic pretreatment could be an efficient approach to enhancing the enzymolysis and improving the functional properties of SPP. Therefore, tri-frequency ultrasound technology can be applied industrially to enhance enzyme reaction process.

Design and functional preliminary investigation of recombinant antigen EgG1Y162-EgG1Y162 against Echinococcus granulosus.

In the early stage, our research group cloned Echinococcus granulosus-specific antigen, EgG1Y162, from protoscolex and adult worms of E. granulosus. In order to enhance the immunogenicity of the vaccine, we prepared a recombinant vaccine by tandemly linking EgG1Y162, splicing the protein and linker at the gene level. This approach is expected to improve the immunogenicity of the vaccine by enhancing the molecular weight of the protein and increasing the antigenic epitopes. Bioinformatics was used to predict the physicochemical properties, transmembrane domain, protein structure, and T-/B-cell antigenic epitope of different recombinant proteins, EgG1Y162-linker-EgG1Y162. Finally, the linker sequence, "GGGGSGGG," which had the least influence on the migration of recombinant protein T/B epitope and can fold normally in series with EgG1Y162, was selected to design the recombinant vaccine. The plasmid was produced using genetic engineering techniques, and the recombinant protein, EGG1Y162-GGGGSGGG-EgG1Y162, was induced to be expressed and purified. EgG1Y162-GGGGSGGG-EgG1Y162 was identified to be correctly expressed with 100% specificity. Compared with EgG1Y162, EgG1Y162-GGGGSGGG-EgG1Y162 was more likely to promote dendritic cell maturation. EgG1Y162-GGGGSGGG-EgG1Y162 was speculated to have the potential to improve antigen immunogenicity by increasing the molecular weight and antigenic epitope.

Cloning and identification of the CTLA-4IgV gene and functional application of vaccine in Xinjiang sheep.

Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is an important surface molecule of activated T cells that has a strong affinity with the B7 molecule on the surface of antigen-presenting cells. Among these molecules, the CTLA-4 extracellular region (CTLA-4 IgV) may be used as a novel immune adjuvant molecule for delivering antigens and inducing strong humoral and cellular immune responses. In this study, bioinformatics analysis was performed to determine and clone the extracellular region of Xinjiang sheep CTLA-4 (NM_001009214). The CTLA-4 IgV gene was amplified and ligated into the pMD19-T vector, and the positive bacteria were screened by blue-white spots for sequencing and comparison. The correctly sequenced CTLA-4 IgV was digested and then ligated into the prokaryotic expression vector pET-30a(+). The plasmid pET30a-CTLA-4 IgV was constructed to induce the expression of the recombinant protein CTLA-4 IgV. Thereafter, CTLA-4 IgV was identified. Clustal X multiple sequence alignment revealed that the protein sequence of Xinjiang sheep CTLA-4 IgV was different from that of the known CTLA-4 extracellular region. The 3D protein structure of Xinjiang sheep CTLA-4 IgV was constructed via the bioinformatics method. Subsequently, molecular docking between the Xinjiang sheep CTLA-4 IgV protein and the B7 molecule was conducted. Results revealed multiple binding sites in the extracellular region of Xinjiang sheep CTLA-4, and two multiple interactions ensured stable binding after docking. The functionality of the Xinjiang sheep CTLA-4 IgV protein was further verified by fusing the CTLA-4 extracellular V region with EgG1Y162, a protective protein from Echinococcus granulosa, and the purified recombinant protein CTLA-4 IgV-EgG1Y162 was expressed with the mouse bone marrow-derived. The addition of the Xinjiang sheep CTLA-4 IgV protein at the amino terminus promoted the binding of EgG1Y162 to dendritic cells (DCs) and increased the maturation rate of these cells, further indicating that the protein could effectively improve the antigen presentation ability of DCs. The CTLA-4 extracellular domain protein of Xinjiang sheep is unique and has the potential to promote the presentation of the fusion protein by DCs as an adjuvant. The cloning and expression of this gene provide new measures and ideas for the preparation of the Xinjiang sheep vaccine to prevent zoonotic diseases.

Identification of Cofilin-1 as a novel biomarker of atopic dermatitis using iTRAQ quantitative proteomics.

BACKGROUND: Atopic dermatitis (AD) is a chronic relapsing inflammatory skin condition; however, little is known about the pathogenesis and serum biomarker of this disease. METHODS: Isobaric tagging for relative and absolute quantitation (iTRAQ) proteomic assay was adopted to identify and quantify the differentially expressed proteins (DEPs) in the serum of AD patients. Bioinformatic analysis, including GO, Reactome, GSEA, PPI, and ssGSEA analysis, were used to identified the enriched pathways, hub proteins and immune cells. The expression level and distribution of hub proteins were confirmed by ELISA and IHC. RESULTS: Sixty-six DEPs were identified with iTRAQ proteomic assay by analyzing serum from AD patients and normal subjects. GO and Reactome analysis shown the alternated pathway were mainly involved in immunity, oxidative stress, and actin cytoskeleton. The GSEA and PPI network analysis among the DEPs were carried out and identified Cofilin-1 and profilin-1 as the core components of this network. Additionally, the disruption of Th1/Th2/Th17 cell balance and the significantly reducing of Treg, MDSC, and γδT cells was also found in AD patients using the ssGSEA analysis. Further ELISA and IHC assay validated the significantly elevated expression of Cofilin-1 in AD patients. CONCLUSION: Our results suggested that Cofilin-1 may serve as a novel biomarker for AD diagnosis.

Losartan ameliorates renal interstitial fibrosis through metabolic pathway and Smurfs-TGF-ß/Smad.

The genesis and development of renal fibrosis involve a variety of pathways closely related to inflammation, cytokines, oxidative stress and metabolic abnormalities. Renal fibrosis is the result of a complex combination of a variety of lesions. Epithelial-mesenchymal transdifferentiation (EMT) of renal tubular epithelial cells is considered the key to renal fibrosis. Losartan is a typical Angiotensin II (ANG II) receptor antagonist and relaxes blood vessels. In this study, we investigated the effects of losartan on Unilateral Ureteral Obstruction (UUO) model mice by studying the changes in the TGF-ß/Smad and metabolomics. Male C57BL/6 J mice were intervened with the UUO model and given losartan (10, 20, 30 mg/kg/d) for 28 consecutive days. The results showed that losartan could reduce UUO-induced abnormal serum metabolic spectrum and renal function. It could also improve renal tubular-interstitial injury and fibrosis by reducing tubulointerstitial dilation and collagen deposition. In addition, losartan promoted the expression of Smurf2 and Smurf1, i.e., Smad7 and E3 ubiquitin-linked enzymes, in the nucleus to degrade the type I receptor of TGF-ß1 (TßR-I) and P-Smad2/3 to inhibit renal tubular epithelial cells EMT. In summary, these findings indicated that losartan could regulate the TGF-ß/Smad and metabolic pathway in UUO model mice through ubiquitination to reduce renal fibrosis.

Shenkang Injection for Treating Renal Fibrosis-Metabonomics and Regulation of E3 Ubiquitin Ligase Smurfs on TGF-ß/Smads Signal Transduction.

At present, TGF-ß is the most critical fibrogenic factor known. Smad ubiquitin ligase Smurfs play an important role in the regulation of the TGF-/Smads signaling pathway, which is linked to metabolite changes in renal fibrosis. Previous studies have shown that Shenkang injection can prevent and treat chronic kidney disease through multiple channels of action. However, the precise relationship between Shenkang injection and the regulation of the TGF-/Smads signaling pathway in the treatment of chronic kidney disease is unknown. Here, we evaluated the pharmacological effects of Shenkang injection on ubiquitination and metabolic changes of the TGF-ß/Smads signaling pathway in UUO mice using pathology-related indicators, immunoprecipitation, subcellular co-location, and metabonomics analysis. Our findings indicate that Shenkang injection can promote nuclear translocation of Smurf1 and Smurf2 to TGF- membrane receptors TR-I and Smad2 and ubiquitinated degradation of these proteins. Furthermore, the formation of TßR-I/TßR-II, TßR-I/Smad2, and TßR-I/Smad3 complexes was inhibited to negatively regulate the TGF-ß/Smad signaling pathway induced renal tubular epithelial transdifferentiation (EMT). The EMT process is not very relevant in vivo, although it is clear that TGF-ß induces EMT in cultured cells, which has been demonstrated by numerous teams around the world. However, this is not the case with the in vivo models of kidney fibrosis, especially UUO. In addition, Shenkang injection can improve amino acid metabolism, purine metabolism, and fatty acid metabolism disorders.

Preoperative and Noninvasive Prediction of Gliomas Histopathological Grades and IDH Molecular Types Using Multiple MRI Characteristics.

Background and Purpose: Gliomas are one of the most common tumors in the central nervous system. This study aimed to explore the correlation between MRI morphological characteristics, apparent diffusion coefficient (ADC) parameters and pathological grades, as well as IDH gene phenotypes of gliomas. Methods: Preoperative MRI data from 166 glioma patients with pathological confirmation were retrospectively analyzed to compare the differences of MRI characteristics and ADC parameters between the low-grade and high-grade gliomas (LGGs vs. HGGs), IDH mutant and wild-type gliomas (IDHmut vs. IDHwt). Multivariate models were constructed to predict the pathological grades and IDH gene phenotypes of gliomas and the performance was assessed by the receiver operating characteristic (ROC) analysis. Results: Two multivariable logistic regression models were developed by incorporating age, ADC parameters, and MRI morphological characteristics to predict pathological grades, and IDH gene phenotypes of gliomas, respectively. The Noninvasive Grading Model classified tumor grades with areas under the ROC curve (AUROC) of 0.934 (95% CI=0.895-0.973), sensitivity of 91.2%, and specificity of 78.6%. The Noninvasive IDH Genotyping Model differentiated IDH types with an AUROC of 0.857 (95% CI=0.787-0.926), sensitivity of 88.2%, and specificity of 63.8%. Conclusion: MRI features were correlated with glioma grades and IDH mutation status. Multivariable logistic regression models combined with MRI morphological characteristics and ADC parameters may provide a noninvasive and preoperative approach to predict glioma grades and IDH mutation status.

Emerging role of TWEAK-Fn14 axis in lupus, a disease related to autoimmunity and fibrosis.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder. Lupus nephritis (LN) is one of the severe clinical implications in SLE, and this was relates to fibrosis in the kidney. As an important marker in the tumor necrosis factor (TNF) superfamily, TNF-like weak inducer of apoptosis (TWEAK) has been given much attention with respect to its role in regulating pro-inflammatory immune response. Fibroblast growth factor-inducible 14 (Fn14), the sole receptor for TWEAK, has been found expressed in different immune and non-immune cells. TWEAK binds to Fn14, and then regulates inflammatory components production via downstream signaling pathways. To date, dysregulated expression of TWEAK, Fn14 has been reported in SLE, LN patients, and in vivo, in vitro studies have discussed the significant role of TWEAK-Fn14 axis in SLE, LN pathogenesis, partly through mediating the fibrosis process. In this review, we will discuss the association of TWEAK-Fn14 axis in lupus. Understanding the relationship will better realize the potential for making TWEAK-Fn14 as a marker for the diseases, and will help to give many clues for targeting them in treatment of lupus in the future.

Activation of 5-HT1 receptor in lateral habenula impaired contextual fear memory and hippocampal LTP in rat.

Serotonin (5-hydroxytraptamine, 5-HT) is a neurotransmitter plays important roles in emotion and motivation. The action of 5-HT varies across nucleus and the receptor sub-types. Lateral habenula (LHb) in a brain area reciprocally connects with raphe nucleus and plays important roles in emotion and depression. In this study, we aimed to study the role of 5-HT1 receptor in LHb on fear learning. 15 min before or immediate after the fear conditioning, 5-Carboxyamidotrypamine maleate salt (5-CT), an agonist of 5-HT1 receptor, was bilaterally delivered into LHb (1 µg/µl, 1 µl/side) in rats. We found that activation of 5-HT1 receptor in LHb impaired the acquisition but not consolidation of fear memory in rats, which was accompanied by impaired long-term potentiation (LTP) and decreased phosphorylation of α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor (AMPAR) subunit 1 (GluA1) at the Ser845 site in hippocampus. In addition, 5-CT decreased the time spent in center area of the open field and time spent in open arm in elevated plus maze. These results suggest that activation of 5-HT1 receptor in LHb impaired acquisition of hippocampal dependent fear memory and increased anxiety- like behavior in rats.

Tumor organoid models in precision medicine and investigating cancer-stromal interactions.

Tumor development and progression require chemical and mechanical cues derived from cellular and non-cellular components in the tumor microenvironment, including the extracellular matrix (ECM), cancer-associated fibroblasts (CAFs), endothelial cells, and immune cells. Therefore, it is crucial to develop tissue culture models that can mimic in vivo cancer cell-ECM and cancer-stromal cell interactions. Three-dimensional (3D) tumor culture models have been widely utilized to study cancer development and progression. A recent advance in 3D culture is the development of patient-derived tumor organoid (PDO) models from primary human cancer tissue. PDOs maintain the heterogeneity of the primary tumor, which makes them more relevant for identifying therapeutic targets and verifying drug response. Other significant advances include development of 3D co-culture assays to investigate cell-cell interactions and tissue/organ morphogenesis, and microfluidic technology that can be integrated into 3D culture to mimic vasculature and blood flow. These advances offer spatial and temporal insights into cancer cell-stromal interactions and represent novel techniques to study tumor progression and drug response. Here, we summarize the recent progress in 3D culture and tumor organoid models, and discuss future directions and the potential of utilizing these models to study cancer-stromal interactions and direct personalized treatment.

A review on the efficacy and mechanism of action of Shenkang injection against chronic kidney disease.

Chronic kidney disease (CKD) is one of the most common conditions which significantly increases the risk for serious health outcomes. Epidemiological investigations have shown that CKD has become a serious global health problem. At present, there are no treatments for CKD, thus the need for an effective and safe treatment for this condition. Shenkang Injection (SKI), which is an herbal medication in Chinese Medicine, has been used in the management and treatment of CKD and has achieved favorable therapeutic effects. The purpose of this paper is to review the clinical efficacy, mechanism of action, and safety profile of SKI when used in CKD, and to provide comprehensive potential evidence for its clinical application.

Renal protective effects of astragaloside IV, in diabetes mellitus kidney damage animal models: A systematic review, meta-analysis.

Astragaloside IV (ASIV) is the essential active component of astragalus that has diverse biological activities. Previous research has suggested its potentially beneficial effects on diabetic nephropathies. However, its effects and protective mechanism remain unclear. In this study, we conducted a preclinical systematic review to evaluate the efficacy and potential mechanisms of ASIV in reducing kidney damage in diabetes mellitus (DM) models. Studies were searched from nine databases until January 2020. A random-effects model was used to calculate combined standardised mean difference estimates and 95 % confidence intervals. Risk of bias of studies was assessed using the Systematic Review Center for Laboratory Animal Experimentation risk of bias tool 10-item checklist. RevMan 5.3 software was used for statistical analysis. Twenty-three studies involving 562 animals were included in the meta-analysis. Studies quality scores ranged from 2 to 5. The ASIV group induced a marked decrease in serum creatinine (P < 0.00001), blood urea nitrogen (P < 0.00001), 24-h urine protein (P < 0.00001) and pathological score (P < 0.001) compared with the control group. The determined potential mechanisms of ASIV action were relieving oxidative stress, delaying renal fibrosis, anti-apoptosis and anti-inflammatory action. We conclude that ASIV exerts renal protective effects in animals with DM through multiple signalling pathways.