BACKGROUND: Microsatellite instability-high (MSI-H) is a form of genomic instability present in 15% of colorectal cancer (CRC) cases. Several differential gene analyses have been conducted on CRC; however, none have specifically explored the differentially expressed genes in MSI-H CRC. Research on the different gene expressions between MSI-H CRC and microsatellite stable (MSS) CRC, and their different patterns of metastasis will provide invaluable insights for diagnosis, prognosis, and treatment. METHODS: In this study, the differential expression of 46,602 genes were analyzed across 613 different tissue samples from The Cancer Genome Atlas (TCGA)-colon adenocarcinoma (COAD) and TCGA-rectum adenocarcinoma (READ) as part of a gene association analysis. R package TCGAbiolinks (version 2.18.0) was used to download the data set, and DESeq2 (version 1.30.1) was used for the differential gene analysis. The resulting genes were then analyzed for shared pathways with R package clusterProfiler (version 3.0.4). RESULTS: A total of 237 significantly differentially expressed genes (P(adj)<0.05) were found between MSI-H and MSS CRC. Differentially expressed genes include insulin like growth factor 2 (IGF2) and fibroblast growth factor 3 (FGF3), and the enriched pathways mostly involve hearing, digestive regulation, and neurogenesis.463 differentially expressed genes were found between metastatic and non-metastatic CRC. Notably differentially expressed genes in metastatic CRC include DEAD-box helicase 53 (DDX53) and adiponectin, C1Q and collagen domain containing (ADIPOQ), and enriched pathways include the immune system, cell adhesion, and cell signaling. For MSI-H CRC, a total of 34 genes were significantly differently expressed between metastatic and non-metastatic CRC. These include notum, palmitoleoyl-protein carboxylesterase (NOTUM), serpin family B member 2 (SERPINB2), and several keratin (KRT) genes, and the pathway analysis showed the major enrichment of the hormonal and secretion and regulation pathways. Of the differentially expressed genes in metastatic CRC, 25 were immunity related and include fatty acid binding protein 4 (FABP4), and the pathway analysis showed the enrichment of humoral immunity and lymphocyte regulation. CONCLUSIONS: Of the biologically plausible differentially expressed genes, the most notable were NOTUM, KRT6A, KRT14, SERPINB2, and serum amyloid A1 (SAA1). NOTUM, KRT6A, and KRT14 are active in the Wnt pathway. All five are also involved in various inflammation pathways.
Title: Serum levels of IL-12, IL-18, and IL-21 are indicators of viral load in patients chronically infected with HBV Zhou F, Xiong H, Zhen S, Chen A, Huang M, Luo Y Ref: Brazilian Journal of Medical & Biological Research, 55:e12320, 2022 : PubMed
This study explored the correlation between interleukins (IL)-12, IL-18, and IL-21 and the viral load in patients with chronic hepatitis B virus (HBV). A total of 142 patients were consecutively enrolled. All were hepatitis B surface antigen (HBsAg)-positive for >6 months and did not receive drug therapy. An ELISA kit was used to test the IL-12, IL-18, IL-21, and acetylcholinesterase (AchE) levels in serum samples from chronic HBV patients and healthy control groups. The amounts of IL-12 and IL-18 were highest in the 5-6log10 (high viral load) group, while IL-21 was highest in the 3-4log10 (low viral load) group. Also, the IL-21 amount was decreased in the HBsAg+/HBeAg/HBcAb+ group, and IL-12, IL-18, and IL-21 were decreased in the normal alanine aminotransferase (ALT) group compared to the abnormal ALT group. These data suggested that IL-12, IL-18, and IL-21 serum levels were positively correlated with disease progression and could reflect disease severity for different HBV-DNA loads. Detection of IL-12, IL-18, and IL-21 levels was found to be helpful for evaluating the degree of liver cell damage and predicting the progression of hepatitis.
Title: Repressed OsMESL expression triggers reactive oxygen species mediated broad-spectrum disease resistance in rice Hu B, Zhou Y, Zhou Z, Sun B, Zhou F, Yin C, Ma W, Chen H, Lin Y Ref: Plant Biotechnol J, :, 2021 : PubMed
A few reports have indicated that a single gene confer resistance to bacterial blight, sheath blight, and rice blast. In this study, we identified a novel disease resistance mutant gene, methyl esterase-like (osmesl) in rice. Mutant rice with T-DNA insertion displayed significant resistance to bacterial blight caused by Xanthomonas oryzae pv. oryzae (Xoo), sheath blight caused by Rhizoctonia solani and rice blast caused by Magnaporthe oryzae. Additionally, CRISPR-Cas9 knockout mutants and RNAi lines displayed resistance to these pathogens. Complementary T-DNA mutants demonstrated a phenotype similar to the wild type (WT), thereby indicating that osmesl confers resistance to pathogens. Protein interaction experiments revealed that OsMESL affects reactive oxygen species (ROS) accumulation by interacting with thioredoxin OsTrxm in rice. Moreover, qRT-PCR results showed significantly reduced mRNA levels of multiple ROS scavenging-related genes in osmesl mutants. Nitroblue tetrazolium staining showed that the pathogens cause ROS accumulation, and quantitative detection revealed significantly increased levels of H(2) O(2) in the leaves of osmesl mutants and RNAi lines after infection. The abundance of JA, a hormone associated with disease resistance, was significantly more in osmesl mutants than in WT plants. Overall, these results suggested that osmesl enhances disease resistance to Xoo, R. solani and M. oryzae by modulating the ROS balance.
Alzheimer's disease (AD) is a prevalent neurodegenerative disorder that has multiple causes. Therefore, multiple-target-directed ligands (MTDLs), which act on multiple targets, have been developed as a novel strategy for AD therapy. In this study, novel drug candidates were designed and synthesized by the covalent linkings of tacrine, a previously used anti-AD acetylcholinesterase (AChE) inhibitor, and dipicolylamine, an beta-amyloid (Abeta) aggregation inhibitor. Most tacrine-dipicolylamine dimers potently inhibited AChE and Abeta(1-42) aggregation in vitro, and 13a exhibited nanomolar level inhibition. Molecular docking analysis suggested that 13a could interact with the catalytic active sites and the peripheral anion site of AChE, and bind to Abeta(1-42) pentamers. Moreover, 13a effectively attenuated Abeta(1-42) oligomers-induced cognitive dysfunction in mice by activating the cAMP-response element binding protein/brain-derived neurotrophic factor signaling pathway, decreasing tau phosphorylation, preventing synaptic toxicity, and inhibiting neuroinflammation. The safety profile of 13a in mice was demonstrated by acute toxicity experiments. All these results suggested that novel tacrine-dipicolylamine dimers, especially 13a, have multi-target neuroprotective and cognitive-enhancing potentials, and therefore might be developed as MTDLs to combat AD.
BACKGROUND: Dipeptidyl peptidase-4 (DPP4) is commonly targeted to achieve glycemic control and has potent anti-inflammatory and immunoregulatory effects. Recent structural analyses indicated a potential tight interaction between DPP4 and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), raising a promising hypothesis that DPP4 inhibitor (DPP4i) drugs might be an optimal strategy for treating coronavirus disease 2019 (COVID-19) among patients with diabetes. However, there has been no direct clinical evidence illuminating the associations between DPP4i use and COVID-19 outcomes. AIM: To illuminate the associations between DPP4i usage and the adverse outcomes of COVID-19. METHODS: We conducted a multicenter, retrospective analysis including 2563 patients with type 2 diabetes who were hospitalized due to COVID-19 at 16 hospitals in Hubei Province, China. After excluding ineligible individuals, 142 patients who received DPP4i drugs and 1115 patients who received non-DPP4i oral anti-diabetic drugs were included in the subsequent analysis. We performed a strict propensity score matching (PSM) analysis where age, sex, comorbidities, number of oral hypoglycemic agents, heart rate, blood pressure, pulse oxygen saturation (SpO(2)) < 95%, CT diagnosed bilateral lung lesions, laboratory indicators, and proportion of insulin usage were matched. Finally, 111 participants treated with DPP4i drugs were successfully matched to 333 non-DPP4i users. Then, a linear logistic model and mixed-effect Cox model were applied to analyze the associations between in-hospital DPP4i use and adverse outcomes of COVID-19. RESULTS: After rigorous matching and further adjustments for imbalanced variables in the linear logistic model and Cox adjusted model, we found that there was no significant association between in-hospital DPP4i use (DPP4i group) and 28-d all-cause mortality (adjusted hazard ratio = 0.44, 95%CI: 0.09-2.11, P = 0.31). Likewise, the incidences and risks of secondary outcomes, including septic shock, acute respiratory distress syndrome, or acute organ (kidney, liver, and cardiac) injuries, were also comparable between the DPP4i and non-DPP4i groups. The performance of DPP4i agents in achieving glucose control (e.g., the median level of fasting blood glucose and random blood glucose) and inflammatory regulation was approximately equivalent in the DPP4i and non-DPP4i groups. Furthermore, we did not observe substantial side effects such as uncontrolled glycemia or acidosis due to DPP4i application relative to the use of non-DPP4i agents in the study cohort. CONCLUSION: Our findings demonstrated that DPP4i use is not significantly associated with poor outcomes of COVID-19 or other adverse effects of anti-diabetic treatment. The data support the continuation of DPP4i agents for diabetes management in the setting of COVID-19.
Title: Unexpected extrapyramidal symptoms and pulmonary aspergillosis in exertional heatstroke with fulminant liver failure: a case report Jiao J, Zhou F, Kang H, Liu C, Yang M, Hu J Ref: J Med Case Rep, 11:37, 2017 : PubMed
BACKGROUND: Exertional heatstroke is a life-threatening condition with high mortality because of the rapid progress of multiple organ dysfunction syndrome even if aggressive treatments are initiated rapidly. Mild to moderate hepatic injury is common in exertional heatstroke, while fulminant liver failure is rare. Extrapyramidal symptoms and pulmonary aspergillosis secondary to liver failure induced by exertional heatstroke have never been reported in prior cases. CASE PRESENTATION: A 25-year-old Han Chinese man presented with exertional heatstroke with fulminant liver failure, subsequent pulmonary aspergillosis, and extrapyramidal symptoms. Moreover, he also presented with coma, rhabdomyolysis, acute kidney injury, and disseminated intravascular coagulation. He recovered under conservative treatment including therapeutic plasma exchange plus continuous veno-venous hemofiltration, fluid resuscitation, antibiotics, and other support therapy. CONCLUSIONS: Therapeutic plasma exchange plus continuous veno-venous hemofiltration could be effective for patients with heatstroke who suffer liver failure and other organ failure. Patients with liver failure are at high risk for pulmonary aspergillosis. Movement disorder in these patients might be extrapyramidal symptoms induced by consistent low level of cholinesterase resulted from hepatic injury besides brain injury.
Title: Association of Lp-PLA2 G994T gene polymorphism with risk of ischemic stroke in Chinese population Ni J, Gu H, Hu W, Zhou F, Zhu X, Wang K Ref: J Biochem Mol Toxicol, 31:, 2017 : PubMed
The association between lipoprotein-associated phospholipase A2 (Lp-PLA2) G994T gene polymorphism and the risk of ischemic stroke is unclear. The aim of this study is to investigate the influence of Lp-PLA2 G994T genetic variant on the pathogenesis of ischemic stroke in Chinese population. A total of 348 patients with a clinical diagnosis of ischemic stroke and 260 gender-matched control subjects under physical examination were recruited from hospitals and genotyped for G994T gene polymorphism. The results showed that there was a significant difference in the genotype distribution between the two groups and people with GT or TT genotype were associated with the higher risk of ischemic stroke even after adjusting the effects of potential confounding factors. In addition, both ischemic stroke patients and control subjects carrying T allele showed relatively lower Lp-PLA2 activity and higher oxLDL level. Therefore, Lp-PLA2 G994T gene polymorphism may be an independent risk factor of ischemic stroke in Chinese population.
Using a whole-genome-sequencing approach to explore germplasm resources can serve as an important strategy for crop improvement, especially in investigating wild accessions that may contain useful genetic resources that have been lost during the domestication process. Here we sequence and assemble a draft genome of wild soybean and construct a recombinant inbred population for genotyping-by-sequencing and phenotypic analyses to identify multiple QTLs relevant to traits of interest in agriculture. We use a combination of de novo sequencing data from this work and our previous germplasm re-sequencing data to identify a novel ion transporter gene, GmCHX1, and relate its sequence alterations to salt tolerance. Rapid gain-of-function tests show the protective effects of GmCHX1 towards salt stress. This combination of whole-genome de novo sequencing, high-density-marker QTL mapping by re-sequencing and functional analyses can serve as an effective strategy to unveil novel genomic information in wild soybean to facilitate crop improvement.
Strigolactones (SLs), a newly discovered class of carotenoid-derived phytohormones, are essential for developmental processes that shape plant architecture and interactions with parasitic weeds and symbiotic arbuscular mycorrhizal fungi. Despite the rapid progress in elucidating the SL biosynthetic pathway, the perception and signalling mechanisms of SL remain poorly understood. Here we show that DWARF 53 (D53) acts as a repressor of SL signalling and that SLs induce its degradation. We find that the rice (Oryza sativa) d53 mutant, which produces an exaggerated number of tillers compared to wild-type plants, is caused by a gain-of-function mutation and is insensitive to exogenous SL treatment. The D53 gene product shares predicted features with the class I Clp ATPase proteins and can form a complex with the alpha/beta hydrolase protein DWARF 14 (D14) and the F-box protein DWARF 3 (D3), two previously identified signalling components potentially responsible for SL perception. We demonstrate that, in a D14- and D3-dependent manner, SLs induce D53 degradation by the proteasome and abrogate its activity in promoting axillary bud outgrowth. Our combined genetic and biochemical data reveal that D53 acts as a repressor of the SL signalling pathway, whose hormone-induced degradation represents a key molecular link between SL perception and responses.
Title: Complete genome sequence of the probiotic strain Lactobacillus casei BD-II Ai L, Chen C, Zhou F, Wang L, Zhang H, Chen W, Guo B Ref: Journal of Bacteriology, 193:3160, 2011 : PubMed
Lactobacillus casei BD-II, a patented probiotic strain (U.S. patent 7,270,994 B2), was isolated from homemade koumiss in China and has been implemented in the industrial production as starter cultures. Here we report the complete genome sequence of BD-II, which shows high similarity with the well-studied probiotic BL23.
Title: Complete genome sequence of the probiotic bacterium Lactobacillus casei LC2W Chen C, Ai L, Zhou F, Wang L, Zhang H, Chen W, Guo B Ref: Journal of Bacteriology, 193:3419, 2011 : PubMed
Lactobacillus casei LC2W, a patented probiotic strain (Z. Wu, European patent EP 1642963 B1, February 2009), has been isolated from Chinese traditional dairy products and implemented in industrial production as starter culture. Here we present the complete genome sequence of LC2W and the identification of a gene cluster implicated in the biosynthesis of exopolysaccharides.
Salicylic acid-binding protein 2 (SABP2) is essential for the establishment of systemic acquired resistance (SAR) in tobacco; SABP2's methyl salicylate (MeSA) esterase activity is required in healthy systemic tissues of infected plants to release the active defense phytohormone SA from MeSA, which serves as a long-distance signal for SAR. In the current study, we characterize a new gene family from Arabidopsis thaliana encoding 18 potentially active alpha/beta fold hydrolases that share 32-57% identity with SABP2. Of 14 recombinant AtMES (MES for methyl esterase) proteins tested, five showed preference for MeSA as a substrate and displayed SA inhibition of MeSA esterase activity in vitro (AtMES1, -2, -4, -7, and -9). The two genes encoding MeSA esterases with the greatest activity, AtMES1 and -9, as well as AtMES7 were transcriptionally upregulated during infection of Arabidopsis with avirulent Pseudomonas syringae. In addition, conditional expression of AtMES1, -7, or -9 complemented SAR deficiency in SABP2-silenced tobacco, suggesting that these three members of the AtMES family are SABP2 functional homologs (orthologs). Underexpression by knockout mutation and/or RNAi-mediated silencing of multiple AtMES genes, including AtMES1, -2, -7, and -9, compromised SAR in Arabidopsis and correlated with enhanced accumulation of MeSA in the systemic tissue of SAR-induced plants. Together, the data show that several members of the AtMES gene family are functionally homologous to SABP2 and redundant for MeSA hydrolysis and probably SAR. These data suggest that MeSA is a conserved SAR signal in Arabidopsis and tobacco.
