Mechanism Explanation on Improved Cognitive Ability of D-Gal Inducing Aged Mice Model by Lactiplantibacillus plantarum MWFLp-182 via the Microbiota-Gut-Brain Axis.

Gut microbiota can influence cognitive ability via the gut-brain axis. Lactiplantibacillus plantarum MWFLp-182 (L. plantarum MWFLp-182) was obtained from feces of long-living individuals and could exert marked antioxidant ability. Interestingly, this strain reduced the D-galactose-induced impaired cognitive ability in BALB/c mice. To comprehensively elucidate the underlying mechanism, we evaluated the colonization, antioxidant, and anti-inflammatory activities of L. plantarum MWFLp-182, along with the expression of potential genes associated with cognitive ability influenced and gut microbiota. L. plantarum MWFLp-182 enhanced the expression of anti-inflammatory cytokines, reduced the expression of proinflammatory cytokines, and increased tight junction protein expression in the colon. Moreover, L. plantarum MWFLp-182 could modify the gut microbiota. Notably, treatment with L. plantarum MWFLp-182 upregulated the expression of postsynaptic density protein-95, nuclear factor erythroid 2-related factor, nerve growth factor, superoxide dismutase, and brain-derived neurotrophic factor/neuronal nuclei, while downregulating the expression of bcl-2-associated X and malondialdehyde in the hippocampus and upregulating short-chain fatty acids against D-galactose-induced mouse brain deficits. Accordingly, L. plantarum MWFLp-182 could improve cognitive ability in a D-galactose-inducing mouse model.

Resveratrol augments paclitaxel sensitivity by modulating miR-671-5p/STOML2/PINK1/Parkin-mediated autophagy signaling in A549 cell.

BACKGROUND: Paclitaxel (PTX) resistance has become a notable clinical concern of Non-small cell lung cancer (NSCLC). Our study aim is to investigate the effects of Resveratrol (RES) on NSCLC cells that have developed resistance to PTX. The NSCLC cell line A549 was employed in this investigation to establish a PTX-resistant NSCLC cell line, denoted as A549/PTX, and established tumor transplantaton model. The presence of miR-671-5p, Stomatin-like protein 2 (STOML2), and mitophagy biomarkers was evaluated using quantitative teal-time PCR (qRT-PCR) and western blot, The assessment of cell proliferation and apoptosis was conducted through the utilisation of colony formation and flow cytometry assays. The investigation of mitochondrial autolysosomes was conducted using transmission electron microscopy (TEM). Our results showed that the application of RES therapy resulted in a substantial improvement in the sansitivity of A549/PTX cells. RES exhibited an augmentation of apoptosis and a suppression of mitophagy in A549/PTX cells. RES induced an upregulation in the expression of miR-671-5p. This, in turn, leaded to the inhibition of STOML2, a protein that directly interacts with PINK1. In summary, our research indicates that RES improved the susceptibility of A549/PTX cells to PTX through miR-671-5p-mediated STOML2 inhibition.

WD repeat domain 5 promotes the development of late-onset preeclampsia by activating nuclear factor kappa B.

PURPOSE: Over-activation of nuclear factor kappa B (NF-κB) was proven to be involved in the pathogenesis of preeclampsia. However, its regulation mechanism is not clear yet. This paper explored the role of WD repeat domain 5 (WDR5) in the development of late-onset preeclampsia and its relationship with NF-κB. METHODS: WDR5 expression was detected in normal placentas and placentas from late-onset preeclampsia patients. CCK-8 and colony formation assays were conducted to appraise the proliferative ability of trophoblast. Migration and invasion were observed by wound healing and transwell assays. The interaction between WDR5 and NF-κB inhibitor I-kappa-B-alpha (IkBa) was verified by Co-immunoprecipitation analysis. Immunofluorescence was used to analyze the activation of NF-κB. Finally, we tested the role of WDR5 using the mice late-onset preeclampsia model. RESULTS: WDR5 was highly expressed in the placentas of late-onset preeclampsia patients. WDR5 overexpression suppressed cell proliferation, migration, and invasion in trophoblast. WDR5 could interact with IkBa to activate NF-κB. Knockdown of NF-κB counteracted the anti-proliferative and anti-metastatic effects of WDR5 overexpression in trophoblast. In-vivo studies suggested that targeting WDR5 combated late-onset preeclampsia development. CONCLUSIONS: Our finding provides new insights into the role of WDR5 in late-onset preeclampsia development.

Mechanism underlying the effect of Pulsatilla decoction in hepatocellular carcinoma treatment: a network pharmacology and in vitro analysis.

BACKGROUND: Currently, hepatocellular carcinoma (HCC) is associated with a poor prognosis. Moreover, there exist limited strategies for treating HCC. Pulsatilla decoction (PD), a traditional Chinese medicine formula, has been used to treat inflammatory bowel disease and several cancer types. Accordingly, we explored the mechanism of PD in HCC treatment via network pharmacology and in vitro experiments. METHODS: Online databases were searched for gene data, active components, and potential target genes associated with HCC development. Subsequently, bioinformatics analysis was performed using protein-protein interaction and Network Construction and Kyoto Encyclopedia of Genes and Genomes (KEGG) to screen for potential anticancer components and therapeutic targets of PD. Finally, the effect of PD on HCC was further verified by in vitro experiments. RESULTS: Network pharmacological analysis revealed that 65 compounds and 180 possible target genes were associated with the effect of PD on HCC. These included PI3K, AKT, NF-κB, FOS, and NFKBIA. KEGG analysis demonstrated that PD exerted its effect on HCC mainly via the PI3K-AKT, IL-17, and TNF signaling pathways. Cell viability and cell cycle experiments revealed that PD could significantly inhibit cancer cell proliferation and kill HCC cells by inducing apoptosis. Furthermore, western blotting confirmed that apoptosis was mediated primarily via the PI3K-AKT, IL-17, and TNF signaling pathways. CONCLUSION: To the best of our knowledge, this is the first study to elucidate the molecular mechanism and potential targets of PD in the treatment of HCC using network pharmacology.

Mixed medullary­follicular thyroid carcinoma: A case report and literature review.

Papillary thyroid cancer (PTC) and medullary thyroid cancer (MTC) originate from follicular and neuroendocrine parafollicular C cells, respectively. PTC and MTC simultaneously exist in tumors containing both MTC and PTC features in a rare condition known as mixed medullary-follicular thyroid carcinoma (MMFTC). In the present study, a 60-year-old female presented with a small mass on the left side of the neck. Ultrasonography indicated a hyperechoic nodule measuring ~11.9×9.7 mm2 in the left lobe of the thyroid gland. The preoperative calcitonin serum value was elevated and total thyroidectomy and bilateral central compartment lymph node dissection was performed. Histological and immunohistochemical analysis of the tumor demonstrated MMFTC. No metastasis was observed in lymph nodes isolated from the bilateral central compartment. Given the rarity of MMFTC, enhancing understanding and management of such tumors is crucial.

Carbon emission reduction potential assessment in food transportation by urban agriculture: A case study of main urban area of Nanjing, China.

As an emerging urban green infrastructure and continuous productive urban landscape, urban agriculture can increase the resilience of urban food systems and reduce carbon emission in food transportation. However, there are few studies in China on the potential of urban agriculture and its role in carbon emission reduction. With semantic segmentation and spatial analysis method to identify urban agricultural potential spaces on the ground and rooftops based on satellite images and Lidar point cloud data in the main urban area of Nanjing, we estimated their potential in vegetable production and the CO2 emission reduction effect in food transportation. The results showed that there were 2904.39 hm2 of ground and 2976.96 hm2 of rooftops in the study area with the potential to be used for urban agriculture. Under a scenario with 80% potential space utilization, it could produce approximately 225000 t of vegetables per year, which equated to 43.6% of annual vegetable consumption in the study area. Meanwhile, it would reduce CO2 emission in long distance food transportation by 63700 t per year.

Temporal and spatial patterns of habitat of Nipponia nippon in China under the background of climate change.

Crested ibis (Nipponia nippon) is one of the endangered species in the International Union for Conservation of Nature. It is of great significance to pay attention to the changes of its suitable habitat in the context of climate change. Based on the geographical distribution data of crested ibis, the MaxEnt model was used to predict the suitable habitat of crested ibis under current scenario and future climate change. The results showed that the prediction accuracy of MaxEnt model was high, with an AUC value of 0.989. The minimum temperature of the coldest month, the mean temperature of the coldest quarter, and the mean annual rainfall were the dominant environmental factors affecting the habitat of crested ibis. Under current climate scenario, the area of moderately and highly suitable area of Chinese crested ibis was 10.65×104 km2, mainly distributed in Shaanxi, Sichuan, Hubei, Henan, and Gansu. In the future, the suitable habitat area of crested ibis would increase significantly under climate change, mainly distributed in Anhui, Chongqing, Guizhou, Jiangsu, Hunan, Shandong, Shaanxi, Jiangxi, Taiwan, Yunnan, Liaoning, and Fujian. In the SSP126 scenario from 2041 to 2060, the suitable habitat area of crested ibis would reach the maximum, being 139.53×104 km2 higher than that of the current climate scenario, accounting for 19.6% of the land area. This study could provide a basis for policy making on the conservation of crested ibis under global climate change.

Determining the mechanism of pulsatilla decoction for treating gastric cancer: a network pharmacology-based study.

Background and aim: Gastric cancer (GC) is a prevalent malignancy worldwide. Pulsatilla decoction (PD), a traditional Chinese medicine formula, can treat inflammatory bowel disease and cancers. In this study, we explored the bioactive components, potential targets, and molecular mechanisms of PD in the treatment of GC. Methods: We conducted a thorough search of online databases to gather gene data, active components, and potential target genes associated with the development of GC. Subsequently, we conducted bioinformatics analysis utilizing protein-protein interaction (PPI), network construction, and Kyoto Encyclopedia of Genes and Genomes (KEGG) to identify potential anticancer components and therapeutic targets of PD. Finally, the efficacy of PD in treating GC was further validated through in vitro experiments. Results: Network pharmacological analysis identified 346 compounds and 180 potential target genes associated with the impact of PD on GC. The inhibitory effect of PD on GC may be mediated through modulation of key targets such as PI3K, AKT, NF-κB, FOS, NFKBIA, and others. KEGG analysis showed that PD mainly exerted its effect on GC through the PI3K-AKT, IL-17, and TNF signaling pathways. Cell viability and cell cycle experiments showed that PD could significantly inhibit proliferation and kill GC cells. Moreover, PD primarily induces apoptosis in GC cells. Western blotting analysis confirmed that the PI3K-AKT, IL-17, and TNF signaling pathways are the main mechanisms by which PD exerts its cytotoxic effects on GC cells. Conclusion: We have validated the molecular mechanism and potential therapeutic targets of PD in treating GC through network pharmacological analysis, thereby demonstrating its anticancer efficacy against GC.

Prognostic and immune microenvironment analysis of cuproptosis-related LncRNAs in breast cancer.

Breast cancer is the most common tumor and the leading cause of cancer death in women. Cuproptosis is a new type of cell death, which can induce proteotoxic stress and eventually lead to cell death. Therefore, regulating copper metabolism in tumor cells is a new therapeutic approach. Long non-coding RNAs play an important regulatory role in immune response. At present, cuproptosis-related lncRNAs in breast cancer have not been reported. Breast cancer RNA sequencing, genomic mutations, and clinical data were downloaded from The Cancer Genome Atlas (TCGA). Patients with breast cancer were randomly assigned to the train group or the test group. Co-expression network analysis, Cox regression method, and least absolute shrinkage and selection operator (LASSO) method were used to identify cuproptosis-related lncRNAs and to construct a risk prognostic model. The prediction performance of the model is verified and recognized. In addition, the nomogram was used to predict the prognosis of breast cancer patients. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and immunoassay were used to detect the differences in biological function. Tumor mutation burden (TMB) was used to measure immunotherapy response. A total of 19 cuproptosis genes were obtained and a prognostic model based on 10 cuproptosis-related lncRNAs was constructed. Kaplan-Meier survival curves showed statistically significant overall survival (OS) between the high-risk and low-risk groups. Receiver operating characteristic curve (ROC) and principal component analysis (PCA) show that the model has accurate prediction ability. Compared with other clinical features, cuproptosis-related lncRNAs model has higher diagnostic efficiency. Univariate and multivariate Cox regression analysis showed that risk score was an independent prognostic factor for breast cancer patients. In addition, the nomogram model analysis showed that the tumor mutation burden was significantly different between the high-risk and low-risk groups. Of note, the additive effect of patients in the high-risk group and patients with high TMB resulted in reduced survival in breast cancer patients. Our study identified 10 cuproptosis-related lncRNAs, which may be promising biomarkers for predicting the survival prognosis of breast cancer.

Comprehensive analysis of prognosis and immune function of CD70-CD27 signaling axis in pan-cancer.

The immune checkpoint molecule CD70 and its receptor CD27 constitute the signal transduction axis, which is abnormally expressed in many solid tumors and is crucial for T cell co-stimulation and immune escape. Tumor cells regulate CD27 expression in the tumor microenvironment by expressing CD70, which promotes immune escape. Although current research evidence suggests a link between CD70 and tumors, no pan-cancer analysis is available. Using the Cancer Genome Atlas, Gene Expression Omnibus datasets, and online databases, we first explored the potential carcinogenic role of the CD70-CD27 signaling axis in human malignancies. Furthermore, qRT-PCR, Western blot, immunohistochemistry, and a T cell-mediated tumor cell killing assay were used to assess the biological function of the CD70-CD27 signaling axis. CD70 expression is upregulated in most cancers and has an obvious correlation with the prognosis of tumor patients. The expression of CD70 and CD27 is associated with the level of regulatory T cell (Treg) infiltration. In addition, T cell receptor signaling pathways, PI3K-AKT, NF-κB, and TNF signaling pathways are also involved in CD70-mediated immune escape. CD70 mainly regulates tumor immune escape by regulating T cell-mediated tumor killing, with Tregs possibly being its primary T cell subset. Our first pan-cancer study provides a relatively comprehensive understanding of the carcinogenic role of the CD70-CD27 signaling axis in different tumors.

miR-101-3p contributes to the progression of preeclampsia by suppressing WDR5-mediated proliferation and invasion of trophoblast.

BACKGROUND: Decreased proliferation and invasion of trophoblast were proven to be involved in the pathogenesis of preeclampsia (PE). However, the regulatory network has not been clarified yet. This study aimed to explore the role of miR-101-3p in the progression of PE. METHODS: miR-101-3p expression in placentas of pregnant women with or without PE was analyzed by real-time quantitative PCR (RT-qPCR). Trophoblastic HTR-8/SVneo and HPT-8 cell lines were cultured and underwent hypoxia/reoxygenation (H/R) treatment to mimic PE in vitro. Cell proliferation and invasion were analyzed in gain-of and loss-of-function assays. Finally, we undertook in vivo studies to explore effects of miR-101-3p in the PE model. RESULTS: Compared to placentas from patients without PE, miR-101-3p expressed significantly higher in placentas from PE patients, and its level was positively correlated with the severity of patients. In vitro studies found that overexpression of miR-101-3p significantly suppressed cell proliferation and invasion, while knockdown of miR-101-3p reversed the impacts of H/R treatment. Further research showed that the expression of WD repeat domain 5 (WDR5) was significantly lower in placentas from patients with PE, and its level was negatively associated with the severity of patients. In vitro and in vivo studies confirmed that miR-101-3p promoted PE progression through the regulation of WD WDR5 expression. CONCLUSION: Increased expression of miR-101-3p in placenta contributes to the development of PE by suppressing WDR5-mediated proliferation and invasion of trophoblast.

WD repeat domain 5 promotes the development of late-onset preeclampsia by activating nuclear factor kappa B

Purpose: Over-activation of nuclear factor kappa B (NF-κB) was proven to be involved in the pathogenesis of preeclampsia. However, its regulation mechanism is not clear yet. This paper explored the role of WD repeat domain 5 (WDR5) in the development of late-onset preeclampsia and its relationship with NF-κB. Methods: WDR5 expression was detected in normal placentas and placentas from late-onset preeclampsia patients. CCK-8 and colony formation assays were conducted to appraise the proliferative ability of trophoblast. Migration and invasion were observed by wound healing and transwell assays. The interaction between WDR5 and NF-κB inhibitor I-kappa-B-alpha (IkBa) was verified by Co-immunoprecipitation analysis. Immunofluorescence was used to analyze the activation of NF-κB. Finally, we tested the role of WDR5 using the mice late-onset preeclampsia model. Results: WDR5 was highly expressed in the placentas of late-onset preeclampsia patients. WDR5 overexpression suppressed cell proliferation, migration, and invasion in trophoblast. WDR5 could interact with IkBa to activate NF-κB. Knockdown of NF-κB counteracted the anti-proliferative and anti-metastatic effects of WDR5 overexpression in trophoblast. In-vivo studies suggested that targeting WDR5 combated late-onset preeclampsia development. Conclusions: Our finding provides new insights into the role of WDR5 in late-onset preeclampsia development.

Resveratrol regulates PINK1/Parkin-mediated mitophagy via the lncRNA ZFAS1-miR-150-5p-PINK1 axis, and enhances the antitumor activity of paclitaxel against non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is a common malignant subtype of lung cancer with high mortality. Resveratrol (RSV) is a natural molecule that regulates mitochondrial metabolism. Here, we explored the effect of RSV on NSCLC cell mitophagy and paclitaxel (PTX) resistance. LncRNA ZFAS1, miR-150-5p, and PTEN-induced putative kinase 1 (PINK1) expressions in NSCLC cells were analyzed by RT-qPCR. Levels of PINK1, Parkin and autophagy related molecules LC3I and LC3II were assessed by western blot. Mitophagy was demonstrated by transmission electron microscopy. Luciferase reporter assay revealed that miR-150-5p directly interacted with ZFAS1 or PINK1. MTT was performed to test the IC50 of NSCLC cells. Cell proliferation and apoptosis were measured with CCK-8, EdU, and TUNEL assays. A549/PTX cells exhibited a higher mitophagy activity, and chemoresistance, whereas RSV suppressed PTX resistance and mitophagy in NSCLC cells. Furthermore, ZFAS1 was found to be a downstream effector of RSV in NSCLC cells. We next found ZFAS1 directly interacted with miR-150-5p and regulated the expression of a key mitophagy regulator PINK1. In addition, RSV modulated PTX resistance and mitophagy in NSCLC via ZFAS1/miR-150-5p/PINK1 axis. We validate that RSV influences mitophagy and PTX resistance in NSCLC via ZFAS1/miR-150-5p mediated PINK1/Parkin pathway. Combining these 2 drugs may be a new option of NSCLC therapy.

Systematic analysis of the expression profile and prognostic significance of m6A regulators and PD-L1 in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a malignant tumor with poor prognosis. N6-methyladenosine (m6A) modification has dual biological functions in RNA modification and plays an important role in HCC. METHODS: The GEO, TCGA, ONCOMINE, UALCAN, GEPIA, Kaplan-Meier plotter, cBioPortal for Cancer Genomics, STRING and TIMER2 databases were used for bioinformatic analyses. Quantitative polymerase chain reaction and western blotting were used to detect the expression of m6A regulators in HCC tissues. RESULTS: The transcription of m6A regulators was upregulated in patients with HCC, and overexpression of YTHDF1/2, YTHDC1, RBM15 and METTL3 was significantly correlated with clinical stages of HCC. In addition, downregulation of ZC3H13 and METTL14 and upregulation of other m6A regulators were associated with a poor prognosis. A high mutation rate (89%) of m6A regulators was also observed in patients with HCC, and mutations in methylation regulators were associated with poor overall survival and disease-free survival. Finally, the expression of the YTHDF family was significantly associated with immune infiltration in the HCC microenvironment. CONCLUSION: m6A regulators and programmed death-ligand 1 may play an important role in the tumorigenesis and immune invasion and escape of HCC and may be risk factors affecting the survival of patients with HCC.

The roles of RNA N6-methyladenosine in esophageal cancer.

Esophageal cancer is a malignant tumour with a high degree of malignancy and high mortality. Its pathogenesis and treatment strategy remain unclear. N6-methyladenosine (m6A) is important for various biological functions in RNA modification and is currently being investigated extensively. It plays an essential role in RNA modification. m6A modification is a dynamic process that reversibly regulates the target RNA through its regulatory factors and plays an important role in several diseases, especially cancer. However, the role of m6A in esophageal cancer remains elusive. RNA modification and splicing are regulated by RNA methylation regulators called 'writers' (methyltransferases), 'erasers' (demethylases) and 'readers' (modified RNA-binding proteins). These regulatory factors recognise and bind to RNA methylation sites, regulate biological functions such as RNA splicing and translation and influence the occurrence, development, invasion and metastasis of tumours. Considering the importance of m6A modification, we reviewed the regulatory mechanisms, biological functions and therapeutic prospects of m6A RNA methylation regulators in esophageal cancer.

Significance of macrophage infiltration in the prognosis of lung adenocarcinoma patients evaluated by scRNA and bulkRNA analysis.

Purpose: To investigate the significance of macrophage infiltration to the prognosis of lung adenocarcinoma. Methods: R language bioinformatics analysis technology, was used to obtain macrophage infiltration-related module genes through WGCNA (Weighted Gene Co-Expression Network Analysis). Marker genes of macrophage subtypes were identified using single-cell sequencing of lung adenocarcinoma tissue. Risk score models were constructed and validated using external data cohorts and clinical samples. Results: Analysis of cohorts TCGA-LUAD, GSE11969, GSE31210, GSE50081, GSE72094 and GSE8894, revealed a negative correlation between macrophage infiltration and survival. Immunohistochemical analyses of clinical samples were consistent with these data. Based on cell-cluster-markers and TAMs-related-genes, TOP8 genes were obtained (C1QTNF6, CCNB1, FSCN1, HMMR, KPNA2, PRC1, RRM2, and TK1) with a significant association to prognosis. Risk score models including 9 factors (C1QTNF6, FSCN1, KPNA2, GLI2, TYMS, BIRC3, RBBP7, KRT8, GPR65) for prognosis were constructed. The efficacy, stability and generalizability of the risk score models were validated using multiple data cohorts (GSE19188, GSE26939, GSE31210, GSE50081, GSE42127, and GSE72094). Conclusions: Macrophage infiltration negatively correlates with prognosis in patients with lung adenocarcinoma. Based on cell-cluster-markers and TAMs-related-genes, both TOP8 genes (C1QTNF6, CCNB1, FSCN1, HMMR, KPNA2, PRC1, RRM2, TK1) and risk score models using C1QTNF6, FSCN1, KPNA2, GLI2, TYMS, BIRC3, RBBP7, KRT8, GPR65 could predict disease prognosis.

Ozone pollution in the plate and logistics capital of China: Insight into the formation, source apportionment, and regional transport.

As the logistics and plate capital of China, the sources and regional transport of O3 in Linyi are different from those in other cities because of the significant differences in industrial structure and geographical location. Twenty-five ozone pollution episodes (OPEs, 52 days) were identified in 2021, with a daily maximum 8-h moving average O3 concentration (O3-MDA8) of 184.5 ± 22.5 µg/m3. Oxygenated volatile organic compounds (OVOCs) and aromatics were the dominant contributors to ozone formation potential (OFP), with contributions of approximately 23.5-52.7% and 20.0-40.8%, respectively, followed by alkenes, alkanes, and alkynes. Formaldehyde, an OVOC with high concentrations emitted from the plate industry and vehicles, contributed the most to OFP (22.7 ± 5.5%), although formaldehyde concentrations only accounted for 9.4 ± 2.7% of the total non-methane hydrocarbon (NMHC) concentrations. The source apportionment results indicated that the plate industry was the dominant O3 contributor (27.0%), followed by other sources (21.6%), vehicle-related sources (18.0%), solvent use (16.9%), liquefied petroleum gas (LPG)/natural gas (NG) (8.8%), and combustion sources (7.7%). Therefore, there is an urgent need to control the plating industry in Linyi to mitigate O3 pollution. The backward trajectory, potential source contribution function (PSCF), and concentration weighted trajectory (CWT) models were used to identify the air mass pathways and potential source areas of air pollutants during the OPEs. O3 pollution was predominantly affected by air masses that originated from eastern and local regions, while trajectories from the south contained the highest O3 concentrations (207.0 µg/m3). The potential source area was from east and south Linyi during the OPEs. Therefore, it is critical to implement regional joint prevention and control measures to lower O3 concentrations.

Whey protein and xylitol complex alleviate type 2 diabetes in C57BL/6 mice by regulating the intestinal microbiota.

Type 2 diabetes (T2D) is a metabolic disorder that has become a major threat to public health. Epidemiological and experimental studies have suggested that whey protein isolate (WPI) and xylitol (XY) play an important role on T2D. This manuscript hypothesizes the supplementation of whey protein and xylitol complex (WXY) has the hypoglycemic and hyperlipidemia effect of T2D mice induced by the conjoint action of a high-fat diet and streptozotocin (STZ) by modulating of intestinal microbiota. The mice with diabetes displayed higher levels of fasting blood glucose (FBG), insulin, glycosylated hemoglobin, total triglycerides, total cholesterol, aspartate aminotransferase, alanine aminotransferase and other serum parameters than the normal mice. Treatment with WXY for 6 weeks significantly modulated the levels of FBG and insulin, improved insulin sensitivity, pancreas impairment and liver function in T2D mice, and the effect was better than that observed with WPI and XY groups. Moreover, supplementation with WXY significantly changed the diversity and composition of the intestinal microbiota in T2D mice and restored the intestinal bacteria associated with T2D (Firmicutes, Bacteroidetes, and Lactobacillus). This may be a potential mechanism for alleviating T2D symptoms. Spearman correlation analysis showed that the relative abundances of specific genera (Turicibacter, Lachnospiraceae_NK4A136_group, Lactobacillus, Candidatus_Saccharimonas, Faecalibaculum and Coriobacteriaceae_UCG-002) were correlated with the levels of blood glucose and serum parameters. Therefore, WXY may be considered a promising dietary supplement for T2D treatment in the future.

Role of N6-Methyladenosine Methylation Regulators in the Drug Therapy of Digestive System Tumours.

Digestive system tumours, including stomach, colon, esophagus, liver and pancreatic tumours, are serious diseases affecting human health. Although surgical treatment and postoperative chemoradiotherapy effectively improve patient survival, current diagnostic and therapeutic strategies for digestive system tumours lack sensitivity and specificity. Moreover, the tumour's tolerance to drug therapy is enhanced owing to tumour cell heterogeneity. Thus, primary or acquired treatment resistance is currently the main hindrance to chemotherapy efficiency. N6-methyladenosine (m6A) has various biological functions in RNA modification. m6A modification, a key regulator of transcription expression, regulates RNA metabolism and biological processes through the interaction of m6A methyltransferase ("writers") and demethylase ("erasers") with the binding protein decoding m6A methylation ("readers"). Additionally, m6A modification regulates the occurrence and development of tumours and is a potential driving factor of tumour drug resistance. This review systematically summarises the regulatory mechanisms of m6A modification in the drug therapy of digestive system malignancies. Furthermore, it clarifies the related mechanisms and therapeutic prospects of m6A modification in the resistence of digestive system malignancies to drug therapy.

The non-covalent interactions between whey protein and various food functional ingredients.

In daily diet, Whey protein (WP) is often coexisted with various Food functional ingredients (FFI) such as proteins, polyphenols, polysaccharides and vitamins, which inevitably affect or interact with each other. Generally speaking, they may be interact by two different mechanisms: non-covalent and covalent interactions, of which the former is more common. We reviewed the non-covalent interactions between WP and various FFI, explained the effect of each WP-FFI interaction, and provided possible applications of WP-FFI complex in the food industry. The biological activity, physical and chemical stability of FFI, and the structure and functionalities of WP were enhanced through the non-covalent interactions. The development of non-covalent interactions between WP and FFI provides opportunities for the design of new ingredients and biopolymer complex, which can be applied in different fields. Future research will further focus on the influence of external or environmental factors in the food system and processing methods on interactions.