Neoadjuvant chemotherapy is linked to an amended anti-tumorigenic microenvironment in gastric cancer.

BACKGROUND: Neoadjuvant chemotherapy (NAC) is a frequently intervention for patients with locally advanced gastric cancer (GC). Nevertheless, its impact on the tumor immune microenvironment remains unclear. METHODS: We used immunohistochemistry to identify T-cell subpopulations, tumor-associated neutrophils (TANs), and tumor-associated macrophages (TAMs) in the GC microenvironment (GCME) among paired samples (pre-chemotherapy and post-chemotherapy) from 48 NAC-treated patients. Multiplex immunofluorescence (mIF) was performed to assess immune biomarkers, including CK, CD4, CD8, FOXP3, PD1, PD-L1, CD163, CD86, myeloperoxidase and Arginase-1 in paired samples from 6 GC patients whose response to NAC were rigorously defined. RESULTS: NAC was intricately linked to enhanced CD8+:CD4+ ratio, reduced CD163+ M2-like macrophages, augmented CD86+ M1: CD163+ M2-like macrophage ratio, and diminished FOXP3+ regulatory T cells (T-regs) and TANs density. Based on mIF, PD1+CD8+T-cells, FOXP3+T-regs, PD-L1+ TANs, and CD163+ M2-like macrophages exhibited marked reduction and greater co-localization with tumor cells following NAC. The pre-NAC FOXP3+ T-regs and CD163+ M2-like macrophages content was substantially elevated in the response cohort, whereas, the post-NAC CD8+:CD4+ and CD86+ M1: CD163+ M2-like macrophage ratios were intricately linked to the tumor pathologic response. We observed greater CD163+ M2-like macrophages and tumor cells co-localization following NAC, which was correlated with tumor pathologic response. Lastly, multivariate analysis revealed that post-NAC CD8+:CD4+ and CD86+ M1: CD163+ M2-like macrophage ratios were stand-alone indicators of positive patient prognosis. CONCLUSIONS: NAC converts the GCME to an anti-tumorigenic state that is conducive to enhanced patient outcome. These finding can significantly benefit the future planning of highly efficacious and personalized GC immunotherapy.

An Energy Efficient and Reliable Multipath Transmission Strategy for Mobile Wireless Sensor Networks.

Multipath data transmission is a key problem that needs to be solved urgently in wireless sensor networks. In this paper, sensor node failure, link failure, energy exhaustion, and external interference affect the stability and reliability of network data transmission. A multipath transmission strategy for wireless sensor networks based on improved shuffled frog leaping algorithm is proposed. A mathematical model of multipath transmission in wireless sensor networks is established. In the shuffled frog leaping algorithm, combined with the transition probability in the particle swarm optimization algorithm, random individuals in the subgroup are introduced to assist the search when updating the frog individual position, which improves the algorithm's ability to jump out of the local optimum and improves the quality of the optimization algorithm solution. The model is applied to multipath transmission in wireless sensor networks. Then, the shuffled frog leaping algorithm is used to update, divide, and reorganize the sensor nodes to select the optimal node to establish the optimal transmission path and improve the stability and reliability of the network. Simulation experiments show that the algorithm in this paper can ensure the reliability of data transmission, reduce the network packet loss rate and network energy consumption, and reduce the average delay of data transmission.

A Data Collection Method for Mobile Wireless Sensor Networks Based on Improved Dragonfly Algorithm.

For the sensing layer of the Internet of Things, the mobile wireless sensor network has problems such as limited energy of the sensor nodes, unbalanced energy consumption, unreliability, and long transmission delay in the data collection process. It is proved by mathematical derivation and theory that this is a typical multiobjective optimization problem. In this paper, the optimization goal is to minimize the energy consumption and improve the reliability under time-delay constraints and propose a path optimization mechanism to optimize the mobile Sink of mobile wireless sensor networks based on the improved dragonfly optimization algorithm. The algorithm takes full advantage of the abundant storage space, sufficient energy, and strong computing power of the mobile Sink to ensure network connectivity and improve network communication efficiency. Through simulation comparison and analysis, compared with random movement method, artificial bee colony algorithm, and basic dragonfly optimization algorithm, the energy consumption of the network is reduced, the lifespan of the network is increased, and the connectivity and transmission delay of the network are improved. The proposed algorithm balances the energy consumption of the sensors nodes to meet the network service quality and improve the reliability of the network.

Data Collection Strategy Based on OSELM and Gray Wolf Optimization Algorithm for Wireless Sensor Networks.

In order to effectively reduce the energy consumption, improve the efficiency of data collection in HWSNs, and prolong the lifetime of the overall network, the clustering method is one of the most effective methods in the data collection methods for HWSNs. The data collection strategy of HWSNs based on the clustering method mainly includes three stages: (1) selecting the appropriate cluster head, (2) forming between clusters, and (3) transferring data between clusters. Among them, the selection of the cluster heads in the first stage. The optimal number of cluster heads in the formation of clusters in the second stage is the core and key to the clustering data collection of HWSNs. In the stage of cluster head selection, a data collection strategy for HWSNs based on the clustering method is proposed. Sink establishes an extreme learning machine neural network model. The cluster member nodes select cluster heads based on the remaining energy of the sensor node, the number of the neighbor node, and the distance to the sink. The best cluster head node is selected through the adaptive learning of the online sequence extreme learning machine. Through comprehensive consideration of various factors to complete the clustering process, the gray wolf algorithm is used to optimize the number of clusters, balance the effect of clustering, and improve the efficiency of data collection while reducing energy consumption. An energy efficient and reliable clustering data collection strategy for HWSNs based on the online sequence extreme learning machine and the gray wolf optimization algorithm is proposed in this paper. The simulation results show that the proposed algorithm not only significantly improves the efficiency of the data collection and reduces energy consumption but also comprehensively improves the reliability of the network and prolongs the network's lifetime.

Helicobacter pylori infection is associated with the co-occurrence of bacteria in the oral cavity and the gastric mucosa.

BACKGROUND: Pathogens capable of impacting gastrointestinal tract tumor development are located in the oral cavity, but whether these oral bacteria are able to colonize the gastric mucosa in gastric cancer (GC) patients and whether Helicobacter pylori infection can influence this process remains to be established. METHODS: Microbial 16S rDNA deep sequencing was conducted to characterize bacteria present in paired gastric mucosa and tongue coating samples in 27 patients with superficial gastritis (SG) and 11 GC patients. RESULTS: While the overall composition of the gastric mucosa and tongue coating microbiomes differed substantially, certain bacteria were present in both of these communities. The co-occurrence of bacteria between the tongue coating and gastric mucosa differed significantly between SG and GC patients. Of the 15 most abundant shared oral bacteria genera (the core shared oral bacteria), which were associated with differences in microbiota composition between these tongue coating and gastric mucosa, three were enriched in the gastric mucosa of GC patients relative to SG patients, whereas, 12 were depleted in GC patient samples. Furthermore, the prevalence and relative abundance of these core shared oral bacteria in the gastric mucosa were also linked to H. pylori infection status, and the core shared oral bacteria were also associated with the overall composition of the gastric mucosal microbiome. CONCLUSIONS: Helicobacter pylori infections are linked to the co-occurrence of bacteria in the oral microbiome and the gastric mucosal microbiome. Ectopic colonization of oral microbes may be a primary driver of H. pylori-induced gastric microbial dysbiosis in patients with GC.

Berberine ameliorates renal impairment and inhibits podocyte dysfunction by targeting the phosphatidylinositol 3-kinase-protein kinase B pathway in diabetic rats.

AIMS/INTRODUCTION: Amelioration of renal impairment is the key to diabetic nephropathy (DN) therapy. The progression of DN is closely related to podocyte dysfunction, but the detailed mechanism has not yet been clarified. The present study aimed to explore the renal impairment amelioration effect of berberine and related mechanisms targeting podocyte dysfunction under the diabetic state. MATERIALS AND METHODS: Streptozotocin (35 mg/kg) was used to develop a DN rat model together with a high-glucose/high-lipid diet. Renal functional parameters and glomerular ultrastructure changes were recorded. The alterations of phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt) and phosphorylated Akt in the kidney cortex were determined by western blot. Meanwhile, podocyte dysfunction was induced and treated with berberine and LY294002. After that, podocyte adhesion functional parameters, protein biomarker and the alterations of the PI3K-Akt pathway were detected. RESULTS: Berberine reduces the increased levels of biochemical indicators, and significantly improves the abnormal expression of PI3K, Akt and phosphorylated Akt in a rat kidney model. In vitro, a costimulating factor could obviously reduce the podocyte adhesion activity, including decreased expression of nephrin, podocin and adhesion molecule α3ß1 levels, to induce podocyte dysfunction, and the trends were markedly reversed by berberine and LY294002 therapy. Furthermore, reduction of PI3K and phosphorylated Akt levels were observed in the berberine (30 and 60 µmol/L) and LY294002 (40 µmol/L) treatment group, but the Akt protein expression showed little change. CONCLUSIONS: Berberine could be a promising antidiabetic nephropathy drug through ameliorating renal impairment and inhibiting podocyte dysfunction in diabetic rats, and the underlying molecular mechanisms might be involved in the regulation of the PI3K-Akt signaling pathway.

Renoprotective effect of berberine via regulating the PGE2 -EP1-Gαq-Ca(2+) signalling pathway in glomerular mesangial cells of diabetic rats.

G-protein coupled receptor-mediated pathogenesis is of great importance in the development of diabetic complications, but the detailed mechanisms have not yet been clarified. Therefore, we aimed to explore the roles of the prostaglandin E2 receptor 1 (EP1)-mediated signalling pathway and develop a corresponding treatment for diabetic nephropathy (DN). To create the DN model, rats fed a high-fat and high-glucose diet were injected with a single dose of streptozotocin (35 mg/kg, i.p.). Then, rats were either treated or not with berberine (100 mg/kg per day, i.g., 8 weeks). Cells were isolated from the renal cortex and cultured in high-sugar medium with 20% foetal bovine serum. Prostaglandin E2 (PGE2 ) levels were determined by ELISA, and cells were identified by fluorescence immunoassay. We measured the biochemical characteristics and observed morphological changes by periodic-acid-Schiff staining. The expression of the EP1 receptor and the roles of GRK2 and ß-arrestin2 were identified using western blotting and flow cytometry. Downstream proteins were detected by western blot, while molecular changes were assessed by ELISA and laser confocal scanning microscopy. Berberine not only improved the majority of biochemical and renal functional parameters but also improved the histopathological alterations. A significant increase in PGE2 level, EP1 membrane expression and Gαq expression, and concentration of Ca(2+) were observed, accompanied by increased GRK2 and ß-arrestin2 levels soon afterwards. Berberine decreased the abnormal concentration of Ca(2+) , the increased levels of PGE2 , the high expression of EP1 and Gαq and suppressed the proliferation of mesangial cells. The EP1 receptor, a critical therapeutic target of the signalling pathway, contributed to mesangial cell abnormalities, which are linked to renal injury in DN. The observed renoprotective effects of berberine via regulating the PGE2 -EP1-Gαq-Ca(2+) signalling pathway indicating that berberine could be a promising anti-DN medicine in the future.

G protein-coupled receptors: potential therapeutic targets for diabetic nephropathy.

Diabetic nephropathy, a lethal microvascular complication of diabetes mellitus, is characterized by progressive albuminuria, excessive deposition of extracellular matrix, thickened glomerular basement membrane, podocyte abnormalities, and podocyte loss. The G protein-coupled receptors (GPCRs) have attracted considerable attention in diabetic nephropathy, but the specific effects have not been elucidated yet. Likewise, abnormal signaling pathways are closely interrelated to the pathologic process of diabetic nephropathy, despite the fact that the mechanisms have not been explored clearly. Therefore, GPCRs and its mediated signaling pathways are essential for priority research, so that preventative strategies and potential targets might be developed for diabetic nephropathy. This article will give us comprehensive overview of predominant GPCR types, roles, and correlative signaling pathways in diabetic nephropathy.

Renoprotective effects of berberine and its potential effect on the expression of ß-arrestins and intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in streptozocin-diabetic nephropathy rats.

BACKGROUND: Berberine has been shown to exert protective effects against diabetic nephropathy (DN), but the mechanisms involved have not been fully characterized. The aim of the present study was to explore the effects of berberine on the expression of ß-arrestins, intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in DN rat kidneys and investigate the underlying molecular mechanisms. METHODS: To create the DN model, rats fed a high-fat and high-glucose diet were injected with a single dose of streptozotocin (35 mg/kg, i.p.). Then, DN rats were either treated or not with berberine (50, 100, 200 mg/kg per day, i.g., 8 weeks). Periodic acid-Schiff staining was used to evaluate renal histopathological changes. Renal tissue levels of ß-arrestin 1 and ß-arrestin 2 were determined by Western blot analysis, whereas immunohistochemistry was used to determine renal ICAM-1 and VCAM-1 levels. RESULTS: Berberine (100, 200 mg/kg) ameliorated the histopathological changes in the diabetic kidney. Western blot analysis revealed significant increases in ICAM-1 and VCAM-1 levels in the kidneys of DN rats, which were reversed by treatment with 100 and 200 mg/kg berberine. In addition, berberine treatment (50, 100, 200 mg/kg) increased diabetic-induced decreases in ß-arrestin 1 and ß-arrestin 2. CONCLUSIONS: Berberine exhibited renoprotective effects in DN rats. The underlying molecular mechanisms may be associated with changes in the levels and regulation of ß-arrestin expression, as well as ICAM-1 and VCAM-1 levels in the rat kidney.

Renoprotective effects of berberine through regulation of the MMPs/TIMPs system in streptozocin-induced diabetic nephropathy in rats.

Berberine has proven protective effects on diabetic nephropathy, but the mechanism for its effects has not been comprehensively established. Hence, we aimed to explore the renoprotective mechanism of berberine on the accumulation of extracellular matrix, alterations of its major components and corresponding changes in the regulatory system, including the matrix metalloproteinases/tissue inhibitor of matrix metalloproteinases (MMPs/TIMPs) system, in diabetic nephropathy rats. In the experiments, diabetic nephropathy rats were treated with berberine (0, 50, 100, 200 mg/kg) respectively. The protein levels of transforming growth factor-ß1 were then detected by Western blot, while fibronectin and type IV collagen levels were assessed using immunohistochemistry. Changes in the MMP2/9 and TIMP1/2 levels were detected using two forms simultaneously. In addition, we also measured the characteristics and biochemical indicators of the diabetic nephropathy rats. The results showed that berberine could ameliorate the fasting blood glucose, and the majority of biochemical and renal function parameters, but did not have an effect on body weight. Immunohistochemistry and Western blot examination revealed a significant increase in the MMP9 and TIMP1/2 levels, with an obvious decrease in MMP2 expression in the diabetic nephropathy rats. Berberine (100 and 200 mg/kg) could significantly improve the abnormal changes in the MMPs/TIMPs system. Meanwhile, reductions in the transforming growth factor-ß1, fibronectin and type IV collagen expression levels were observed in the berberine treatment groups. Therefore, the renoprotective effects of berberine on diabetic nephropathy might be associated with changes in the extracellular matrix through the regulation of the MMPs/TIMPs system in the rat kidney.

Berberine as a promising anti-diabetic nephropathy drug: An analysis of its effects and mechanisms.

Diabetic nephropathy is a progressive kidney disorder and is pathologically characterized by thickened glomerular and tubular basement membranes, accumulation of the extracellular matrix and increased mesangial hypertrophy. Growing evidence has suggested that diabetic nephropathy is induced by multiple factors, such as dyslipidemia, hyperglycemia, hemodynamic abnormalities and oxidative stress, based on genetic susceptibility. Berberine (BBR; [C20H18NO4](+)), an isoquinoline alkaloid, is the major active constituent of Rhizoma coptidis and Cortex phellodendri. Recent studies have demonstrated that berberine has various pharmacological activities, including lowering blood glucose, regulating blood lipids and reducing inflammation in addition to its antioxidant activity. These findings suggest that berberine has potential applications as a therapeutic drug for diabetic nephropathy, and has significant research value. However, the possible mechanisms have not been fully established. The purpose of this paper is to investigate the renoprotective mechanisms of berberine in diabetic nephropathy and highlight the importance of berberine as a potential therapeutic reagent for diabetic nephropathy treatment.

[Establishment of cell lines derived from skin biopsies of crested ibis (Nipponia nippon) and their biological characteristics].

The crested ibis is among the rarest and most endangered species worldwide. To preserve its genetic resources and conveniently provide materials for biological research, we successfully established two cell lines from biopsies of a male and female adult crested ibis. The cultured cells from both specimens had typical fibroblast morphology. Immunofluorescence staining revealed that the cultured cells strongly expressed the marker of smooth muscle specific α-actin, clearly indicating the cells were from the smooth muscle tissue. Growth property analysis showed that the cells grew well past the first 10 passages and continued growing with reduced proliferation after 15 passages, but ceased by passage 25 as the cells could not grow to form a confluent monolayer. From these two cell lines, we harvested mitotic metaphase chromosomes and conducted different staining, banding, and fluorescent in situ hybridization. Throughout the process, cells maintained normal diploidy, with the karyotypes of these two cell lines being 2n=68, ZZ in the male and 2n=68, ZW in the female. Patterns of Ag staining, C- and G-bands of the crested ibis chromosomes were also studied. Banding analyses and fluorescent in situ hybridization also allowed identification of the sex chromosomes. We suggest that the external implants method for establishing primary cell lines used in this study may also be applicable to other birds, especially similarly endangered avian species.