Attributes of intestinal microbiota composition and their correlation with clinical primary non-response to anti-TNF-α agents in inflammatory bowel disease patients

The largest microbial aggregation in the human body exists in the gastrointestinal tract. The microbiota in the host gastrointestinal tract comprises a diverse ecosystem, and the intestinal microbiota plays a vital role in maintaining gut homeostasis. This study aims to examine whether the gut microbiota influences unresponsiveness to anti-TNF-α treatments in primary nonresponder patients, and consequently identify the responsible microbes as biomarkers of unresponsiveness. Stool samples were collected from a cohort of patients with an established diagnosis of IBD, either ulcerative colitis (UC) or Crohn’s disease (CD), following completion of the induction phase of anti TNF therapy. 16S rRNA sequencing analysis was used to examine the pattern of microbiota communities in fecal samples. The quality and quantity of fecal microbiota were compared in responder and primary nonresponder IBD patients following anti-TNF-α therapy. As per our hypothesis, a difference in gut microbiome composition between the two patient subgroups was observed. A decreased abundance of short-chain fatty acid (SCFA)-producing bacteria, including Anaerostipes, Coprococcus, Lachnospira, Roseburia, and Ruminococcus, was detected in non-responsive patients, which was the hallmark of dysbiosis. Biomarkers of dysbiosis that were identified as predictors of clinical nonresponse, included Klebsiella, Eubacteriaceae, RF32, Bifidobacterium_animalis, and Muribaculaceae—previously known as S24-7. Signature biomarkers showed dramatic alteration in the composition of gut microbiota in patients who demonstrated primary nonresponse to anti-TNF-α agents. Dysbiosis, with features including a dropped biodiversity, augmentation in opportunistic pathogenic microbiota, and a lack of SCFA-producing bacteria, is a prominent feature of the microbiome of primary nonresponders to anti-TNF-α therapy

Escherichia coli Strains in Patients with Inflammatory Bowel Diseases: A Review

Gastrointestinal tract conditions, including inflammatory bowel diseases (IBDs) such as ulcerative colitis (UC) and Crohn’s disease, have been linked to adhesive invasive Escherichia coli (AIEC) pathotypes, with comparable pathogenic properties, although the incidence of AIEC with UC and CD is generally undetermined. While a significant advance has been made in understanding the pathogenic processes of AIEC since it was first characterized a decade ago, the molecular basis that determines the phenotypic features of AIEC pathotypes is still unknown. This article reviews studies that examine the prevalence of E. coli in patients with IBD and discusses its pathophysiological role.</jats:p

Intestinal Macrophages and Intestinal Infection

There has been increased interest in the role played by macrophages in the maintenance of an active immune system and intestinal homeostasis. Nonetheless, they are also responsible for the rise of chronic pathologies such as inflammatory bowel syndrome in the gut. The lack of differentiation of monocytes in the intestines due to disease conditions leads to a fall in the diversity of microbiota and subsequent gut inflammation. Macrophages play a central role in the homeostasis and immunity of the gut, making them potential sources of novel therapies or remedies for inflammatory bowel disease (IBD) patients. To explore this possibility, this research discusses their structure, differentiation, and functionality in an in-depth manner. It will also describe their role in the local intestinal environment and how it changes upon infection. Finally, the paper will outline its conclusions as well as comment on the future outlook of related research.</jats:p

Direct and Indirect Selection for Grain Yield and Grain Weight in Late Generations of Bread Wheat under Drought Stress and Normal Irrigation Environments

Two cycles of pedigree selection for grain yield/plant (GY/P) and grain weight (GW) (100-grain weight) were imposed under drought stress and normal irrigation to study the direct and indirect selection of GY/P and GW in bread wheat. The selection started in the F6-generation (Cycle0-C0) of bread wheat (Triticum aestivum L.) traced back to the cross (Giza 164/Sids 4) of two Egyptian cultivars. The narrow sense heritability was higher under drought than under normal irrigation and increased by selection. Under drought, the observed direct gain after two cycles of selection for GW was 21.51% (p ≤ 0.01), and accompanied with an indirect gain in GY/P of 15.52%. The observed direct gain for GY/P was 17.98% and the indirect gain in GW was 13.81%. Under normal irrigation, the observed direct gain for GW was 12.86% and the indirect gain for GY/P was 16.04%. The direct gain in GY/P was 16.04% and the indirect gain in GW was 11.95%. The genotypic correlations were different in both environments before and after selection. Single trait selection was effective in improving the selection criterion, and selection greatly affected gene associations.</jats:p

Direct and Indirect Selection for Grain Yield and Grain Weight in Late Generations of Bread Wheat under Drought Stress and Normal Irrigation Environments

Two cycles of pedigree selection for grain yield/plant (GY/P) and grain weight (GW) (100-grain weight) were imposed under drought stress and normal irrigation to study the direct and indirect selection of GY/P and GW in bread wheat. The selection started in the F6-generation (Cycle0-C0) of bread wheat (Triticum aestivum L.) traced back to the cross (Giza 164/Sids 4) of two Egyptian cultivars. The narrow sense heritability was higher under drought than under normal irrigation and increased by selection. Under drought, the observed direct gain after two cycles of selection for GW was 21.51% (p &le; 0.01), and accompanied with an indirect gain in GY/P of 15.52%. The observed direct gain for GY/P was 17.98% and the indirect gain in GW was 13.81%. Under normal irrigation, the observed direct gain for GW was 12.86% and the indirect gain for GY/P was 16.04%. The direct gain in GY/P was 16.04% and the indirect gain in GW was 11.95%. The genotypic correlations were different in both environments before and after selection. Single trait selection was effective in improving the selection criterion, and selection greatly affected gene associations

Changes in Metabolite Profiling and Expression Levels of Key Genes Involved in the Terpenoid Biosynthesis Pathway in Garden Sage (Salvia officinalis) under the Effect of Hydrazine Hydrate

Mutagenesis is a highly efficient tool for establishing genetic variation and is widely used for genetic enhancement in various plants. The key benefit of mutation breeding is the prospect of enhancing one or several characteristics of a variety without altering the genetic background. In this study, we exposed the seeds of Salvia officinalis to four concentrations of hydrazine hydrate (HZ), i.e., (0%, 0.1%, 0.2%, and 0.3%) for 6 h. The contents of terpenoid compounds in the S. officinalis plantlets driven from the HZ-treated seeds were determined by GC-MS, which resulted in the identification of a total of 340 phytochemical compounds; 163 (87.48%), 145 (84.49%), 65 (97.45%), and 62 (98.32%), from the four concentrations of HZ (0%, 0.1%, 0.2%, and 0.3%), respectively. Furthermore, we used the qRT-PCR system to disclose the &ldquo;transcriptional control&rdquo; for twelve TPS genes related to terpenoid and terpene biosynthesis, namely, SoGPS, SoMYRS, SoNEOD, SoCINS, SoSABS, SoLINS, SoFPPS, SoHUMS, SoTPS6, SoSQUS, SoGGPS, and SoGA2. Altogether, results are likely to ensure some positive relationship between the concentrations of the chemical mutagen HZ used for treating the seeds, the type and amount of the produced terpenes, and the expression of their corresponding genes

Attributes of intestinal microbiota composition and their correlation with clinical primary nonresponse to anti-TNF-α agents in inflammatory bowel disease patients

The largest microbial aggregation in the human body exists in the gastrointestinal tract. The microbiota in the host gastrointestinal tract comprises a diverse ecosystem, and the intestinal microbiota plays a vital role in maintaining gut homeostasis. This study aims to examine whether the gut microbiota influences unresponsiveness to anti-TNF-α treatments in primary nonresponder patients, and consequently identify the responsible microbes as biomarkers of unresponsiveness. Stool samples were collected from a cohort of patients with an established diagnosis of IBD, either ulcerative colitis (UC) or Crohn’s disease (CD), following completion of the induction phase of anti TNF therapy. 16S rRNA sequencing analysis was used to examine the pattern of microbiota communities in fecal samples. The quality and quantity of fecal microbiota were compared in responder and primary nonresponder IBD patients following anti-TNF-α therapy. As per our hypothesis, a difference in gut microbiome composition between the two patient subgroups was observed. A decreased abundance of short-chain fatty acid (SCFA)-producing bacteria, including Anaerostipes, Coprococcus, Lachnospira, Roseburia, and Ruminococcus, was detected in non-responsive patients, which was the hallmark of dysbiosis. Biomarkers of dysbiosis that were identified as predictors of clinical nonresponse, included Klebsiella, Eubacteriaceae, RF32, Bifidobacterium_animalis, and Muribaculaceae—previously known as S24-7. Signature biomarkers showed dramatic alteration in the composition of gut microbiota in patients who demonstrated primary nonresponse to anti-TNF-α agents. Dysbiosis, with features including a dropped biodiversity, augmentation in opportunistic pathogenic microbiota, and a lack of SCFA-producing bacteria, is a prominent feature of the microbiome of primary nonresponders to anti-TNF-α therapy. </jats:p

Carvacrol instigates intrinsic and extrinsic apoptosis with abrogation of cell cycle progression in cervical cancer cells: Inhibition of Hedgehog/GLI signaling cascade

Recent times have seen a strong surge in therapeutically targeting the hedgehog (HH)/GLI signaling pathway in cervical cancer. HH signaling pathway is reported to be a crucial modulator of carcinogenesis in cervical cancer and is also associated with recurrence and development of chemoresistance. Moreover, our previous reports have established that carvacrol (CAR) inhibited the proliferation of prostate cancer cells via inhibiting the Notch signaling pathway and thus, it was rational to explore its antiproliferative effects in cervical cancer cell lines. Herein, the present study aimed to investigate the anticancer and apoptotic potential of CAR on C33A cervical cancer cells and further explore the underlying mechanisms. We found that CAR significantly suppressed the growth of C33A cells, induced cell cycle arrest, and enhanced programmed cell death along with augmentation in the level of ROS, dissipated mitochondrial membrane potential, activation of caspase cascade, and eventually inhibited the HH signaling cascade. In addition, CAR treatment increased the expression of pro-apoptotic proteins (Bax, Bad, Fas-L, TRAIL, FADDR, cytochrome c) and concomitantly reduced the expression of anti-apoptotic proteins (Bcl-2 and Bcl-xL) in C33A cells. CAR mediates the activation of caspase-9 and -3 (intrinsic pathway) and caspase-8 (extrinsic pathway) accompanied by the cleavage of PARP in cervical cancer cells. Thus, CAR induced apoptosis by both the intrinsic and extrinsic apoptotic pathways. CAR efficiently inhibited the growth of cervical cancer cells via arresting the cell cycle at G0/G1 phase and modulated the gene expression of related proteins (p21, p27, cyclin D1 and CDK4). Moreover, CAR inhibited the HH/GLI signaling pathway by down regulating the expression of SMO, PTCH and GLI1 proteins in cervical carcinoma cells. With evidence of the above results, our data revealed that CAR treatment suppressed the growth of HPV−C33A cervical cancer cells and further elucidated the mechanistic insights into the functioning of CAR.</jats:p