The role of microbiota in the development and treatment of gastric cancer.

The stomach was once considered a sterile organ until the discovery of Helicobacter pylori (HP). With the application of high-throughput sequencing technology and macrogenomics, researchers have identified fungi and fivemajor bacterial phyla within the stomachs of healthy individuals. These microbial communities exert regulatory influence over various physiological functions, including energy metabolism and immune responses. HP is a well-recognized risk factor for gastric cancer, significantly altering the stomach's native microecology. Currently, numerous studies are centered on the mechanisms by which HP contributes to gastric cancer development, primarily involving the CagA oncoprotein. However, aside from exogenous infections such as HP and EBV, certain endogenous dysbiosis can also lead to gastric cancer through multiple mechanisms. Additionally, gut microbiota and its metabolites significantly impact the development of gastric cancer. The role of microbial therapies, including diet, phages, probiotics and fecal microbiota transplantation, in treating gastric cancer should not be underestimated. This review aims to study the mechanisms involved in the roles of exogenous pathogen infection and endogenous microbiota dysbiosis in the development of gastric cancer. Also, we describe the application of microbiota therapy in the treatment and prognosis of gastric cancer.

Vaginal and tumor microbiomes in gynecological cancer (Review).

Cervical, ovarian and endometrial cancer are the three most common types of gynecologic cancer. As a hub, the vagina connects the site of gynecological cancer with the external environment. Lactobacilli participate in the formation of a healthy vaginal microenvironment as the first line of defense against pathogen invasion; a dysbiotic vaginal microenvironment loses its original protective function and is associated with the onset, metastasis, poor efficacy and poor prognosis of gynecological cancer. The early diagnosis of cancer is the key to improve the survival time of patients with cancer. The screening of Porphyromonas, Sneathia and Atopobium vaginae, and other microbial markers, can assist the diagnosis of gynecological cancer, and screen out the high-risk population as early as possible. With the in-depth study of the microbes in tumor tissues, reasearchers have analyzed the immunological associations of microorganisms in tumor tissues. Due to the structural-functional interconnection between the organ of gynecological tumorigenesis and the vagina, the present study aims to review the relationship between vaginal and tumor microorganisms and gynecological cancer in terms of occurrence, screening, treatment and prognosis.

Endothelial depletion of Atg7 triggers astrocyte-microvascular disassociation at blood-brain barrier.

Microvascular basement membrane (BM) plays a pivotal role in the interactions of astrocyte with endothelium to maintain the blood-brain barrier (BBB) homeostasis; however, the significance and precise regulation of the endothelial cell-derived BM component in the BBB remain incompletely understood. Here, we report that conditional knockout of Atg7 in endothelial cells (Atg7-ECKO) leads to astrocyte-microvascular disassociation in the brain. Our results reveal astrocytic endfeet detachment from microvessels and BBB leakage in Atg7-ECKO mice. Furthermore, we find that the absence of endothelial Atg7 downregulates the expression of fibronectin, a major BM component of the BBB, causing significantly reduced coverage of astrocytes along cerebral microvessels. We reveal Atg7 triggers the expression of endothelial fibronectin via regulating PKA activity to affect the phosphorylation of cAMP-responsive element-binding protein. These results suggest that Atg7-regulated endothelial fibronectin production is required for astrocytes adhesion to microvascular wall for maintaining the BBB homeostasis. Thus, endothelial Atg7 plays an essential role in astrocyte-endothelium interactions to maintain the BBB integrity.

Reviewing the role of gut microbiota in the pathogenesis of depression and exploring new therapeutic options.

The relationship between gut microbiota (GM) and mental health is one of the focuses of psychobiology research. In recent years, the microbial-gut-brain axis (MGBA) concept has gradually formed about this bidirectional communication between gut and brain. But how the GM is involved in regulating brain function and how they affect emotional disorders these mechanisms are tenuous and limited to animal research, and often controversial. Therefore, in this review, we attempt to summarize and categorize the latest advances in current research on the mechanisms of GM and depression to provide valid information for future diagnoses and therapy of mental disorders. Finally, we introduced some antidepressant regimens that can help restore gut dysbiosis, including classic antidepressants, Chinese materia medica (CMM), diet, and exogenous strains. These studies provide further insight into GM's role and potential pathways in emotion-related diseases, which holds essential possible clinical outcomes for people with depression or related psychiatric disorders. Future research should focus on clarifying the causal role of GM in disease and developing microbial targets, applying these findings to the prevention and treatment of depression.

Gut Microbes in Gynecologic Cancers: Causes or Biomarkers and Therapeutic Potential.

The human intestine is home to a variety of microorganisms. In healthy populations, the intestinal flora shares a degree of similarity and stability, and they have a role in the metabolism, immunological response, and physiological function of key organs. With the rapid advent of high-throughput sequencing in recent years, several researchers have found that dysbiosis of the human gut microflora potentially cause physical problems and gynecological malignancies among postmenopausal women. Besides, dysbiosis hinders tumor treatment. Nonetheless, the importance of maintaining homeostatic gut microbiota and the effective use of probiotics in the treatment of gynecological malignancies should not be disregarded. Moreover, intestinal flora regulation and the involvement of probiotics as well as associated biologically active substances in gynecological malignancies could be an adjuvant treatment modality related to surgery and chemoradiotherapy in the future. Herein, this article aims to review the potential relationship between gut microorganisms and postmenopausal status as well as gynecologic malignancies; then the relationship between gut microbes and early screening as well as therapeutic aspects. Also, we describe the role of probiotics in the prevention, treatment, and prognosis of gynecologic malignancies.

Copper-Catalyzed Tandem Reactions of 2-Amine-[1,3,5]triazines with Nitriles.

Copper-catalyzed intermolecular annulation of 2-amine-[1,3,5]triazines and aryl nitriles for the synthesis of [1,2,4]triazolo[1,5- a][1,3,5]triazines via N-C bond formation and oxidative N-N coupling [oxidative 3 + 2 cyclization] is presented. A wide range of aryl nitriles, including electron-rich benzonitriles, electron-poor benzonitriles, 2-cyanothiophene, and 4-cyanopyridine, were all functionalized with 2-amine-[1,3,5]triazines. Furthermore, amidation of 2-amine-[1,3,5]triazines via Cu-catalyzed C-CN bond cleavage of phenylacetonitriles is also demonstrated. The reaction occurred in moderate to satisfactory yields and tolerated alkyl- or aryl-substituted 2-amine-[1,3,5]triazines. Aniline, aminopyridine, and aminopyrimidine also afforded the desired products.

Endothelial Atg7 Deficiency Ameliorates Acute Cerebral Injury Induced by Ischemia/Reperfusion.

Ischemic strokes often result in cerebral injury due to ischemia/reperfusion (I/R). Although the local inflammatory responses are known to play a primary role in the brain I/R injury, the underlying mechanism remains unclear. In the current study, we investigated the effect of brain endothelial Atg7 (autophagy related 7) depletion in the acute brain injury induced by ischemia and reperfusion. Endothelial knockout of Atg7 in mice (Atg7 eKO) was found to significantly attenuate both the infarct volume and the neurological defects induced by I/R when compared to the controls. In fact, brain inflammatory responses induced by I/R were alleviated by the Atg7 eKO. Furthermore, an increased expression of pro-inflammatory cytokines, including IL-1ß, IL-6, IL-8, and TNF-α, was observed in brain endothelial cells in response to oxygen/glucose depletion/reoxygenation, which was decreased by the shRNA-mediated Atg7 knockdown. Interestingly, Atg7 knockdown reduced IKKß phosphorylation, leading to NF-κB deactivation and downregulation of the pro-inflammatory cytokines mRNA levels. Further, Atg7 transcriptional regulation function is independent of its role in autophagy. Taken together, our results demonstrated that brain endothelial Atg7 contributes to brain damage during I/R by modulating the expression of pro-inflammatory cytokines. Depletion of Atg7 in brain endothelium has a neuroprotective effect against the ischemia/reperfusion-induced acute cerebral injury during stroke.

Copper-Catalyzed Synthesis of Substituted 2,4-Diamino-1,3,5-triazines from 1,1-Dibromoalkenes and Biguanides.

An efficient copper-catalyzed synthesis of substituted 2,4-diamino-1,3,5-triazines from 1,1-dibromoalkenes and biguanides under mild conditions has been developed. The reaction occurred in moderate to good yields and tolerated alkyl-, heterocyclic-, or aryl-substituted 1,1-dibromoalkenes containing functionalities such as nitriles, ethers, and halogens. Monosubstituted to tetrasubstituted biguanidines also afforded the desired products.

Antinociceptive Effects of AGAP, a Recombinant Neurotoxic Polypeptide: Possible Involvement of the Tetrodotoxin-Resistant Sodium Channels in Small Dorsal Root Ganglia Neurons.

Antitumor-analgesic peptide (AGAP) is a novel recombinant polypeptide. The primary study showed that AGAP 1.0 mg/kg exhibited strong analgesic and antitumor effects. The tail vein administration of AGAP potently reduced pain behaviors in mice induced by intraplantar injection of formalin or intraperitoneal injection of acetic acid, without affecting basal pain perception. To further assess the mechanisms of AGAP, the effects of AGAP on sodium channels were assessed using the whole-cell patch clamp recordings in dorsal root ganglia (DRG) neurons. The results showed that AGAP (3-1000 nM) inhibited the sodium currents in small-diameter DRG neurons in a dose-dependent manner. 1000 nM AGAP could inhibit the current density-voltage relationship curve of sodium channels in a voltage-dependent manner and negatively shift the activation curves. 1000 nM AGAP could reduce the tetrodotoxin-resistant (TTX-R) sodium currents by 42.8% in small-diameter DRG neurons. Further analysis revealed that AGAP potently inhibited NaV1.8 currents by 59.4%, and negatively shifted the activation and inactivation kinetics. 1000 nM AGAP also reduced the NaV1.9 currents by 33.7%, but had no significant effect on activation and inactivation kinetics. Thus, our results demonstrated that submicromolar concentrations of AGAP inhibited TTX-R sodium channel in rat small-diameter DRG neurons. It is concluded that these new results may better explain, at least in part, the analgesic properties of this polypeptide.