Journal of Bio-X Research
Volume 05 · Issue 03 · 2022
J Bio-X Res
- Sections
- Review Article
- Research Article
- Corrigendum
Mucormycosis is a lethal human disease caused by fungi of the order Mucorales. Mucormycosis is caused by fungi mainly belonging to the genera Mucor, Rhizopus, and Lichtheimia, all of which belong to the order Mucorales. The number of individuals with mucormycosis-causing disorders has increased in recent years, hence, leading to the spread of mucormycosis. Throughout the coronavirus disease 2019 (COVID-19) pandemic, numerous cases of mucormycosis in COVID-19-infected patients have been reported worldwide, and the illness is now recognized as COVID-19-associated mucormycosis, with most of the cases being reported from India. Immunocompromised patients such as those with bone marrow sickness and uncontrolled diabetes are at a greater risk of developing mucormycosis. Genes, pathways, and other mechanisms have been studied in Mucorales, demonstrating a direct link between virulence and prospective therapeutic and diagnostic targets. This review discusses several proteins such as high-affinity iron permease (FTR1), calcineurin, spore coat protein (CotH), and ADP-ribosylation factors involved in the pathogenesis of mucormycosis that might prove to be viable target(s) for the development of novel diagnostic and therapeutic methods.
Sclerotinia sclerotiorum (Lib.) de Bary is a necrotrophic plant pathogen that causes cottony rot, watery soft rot, stem rot, white mold, and other disease symptoms in over 700 plant hosts around the world. Destruction of economically important crops, the lack of resistant cultivars, and the general challenge of controlling diseases caused by this broad-based pathogen call for continued research. However, in recent years, mass spectrometry-based proteomics analyses have been used to acquire a fundamental and in-depth molecular understanding of this fungal pathogen. In this review, we describe the characteristics of the Sclerotinia sclerotiorum pathogen and examine its virulence factors, secreted proteins, and host suppression mechanisms. Furthermore, we review recent proteomics studies and extrapolate their primary findings for the identification and functional characterization of Sclerotinia sclerotiorum proteins. Finally, we discuss key findings that shape the understanding of the virulent factors and pathogenesis of Sclerotinia sclerotiorum and outline directions for future proteomic investigations of plant pathogens.
The coronavirus disease 2019 (COVID-19) pandemic was triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a previously unknown strain of coronavirus. To fully understand the consequences and complications of SARS-CoV-2 infections, we have reviewed current literature on coagulation dysfunctions that are related to the disease and vaccination. While COVID-19 is more commonly considered as a respiratory illness, studies indicate that, in addition to respiratory illness, a coagulation dysfunction may develop in individuals after the initial infection, placing them at the risk of developing thrombotic events. Patients who died of COVID-19 had higher levels of D-dimer, a biomarker for blood clot formation and breakdown. Effective treatments for coagulation dysfunctions are critically needed to improve patient survival. On the other hand, antibodies against platelet factor 4 (PF4)/heparin may be found in patients with rare instances of vaccine-induced immunological thrombotic thrombocytopenia (VITT) following vaccination with adenovirus-based vaccines. VITT is characterized by atypical thrombosis and thrombocytopenia, similar to immune-mediated heparin-induced thrombocytopenia (HIT), but with no need for heparin to trigger the immune response. Although both adenovirus-based and mRNA-based vaccines express the Spike protein of SARS-CoV-2, VITT is exclusively related to adenovirus-based vaccines. Due to the resemblance with HIT, the use of heparin is highly discouraged against treating patients with thrombotic thrombocytopenia after SARS-CoV-2 infection or with VITT after vaccination. Intravenous immunoglobulin therapy coupled with anticoagulation is recommended instead. The well-studied anti-PF4 monoclonal antibody RTO, which does not induce pathologic immune complexes in the presence of heparin and has been humanized for a potential treatment modality for HIT, may provide a nonanticoagulant HIT-specific solution to the problem of increased blood coagulation after SARS-CoV-2 infection or the VITT after immunization.
He-Zhao deficiency was originally described as a severe type of nonsyndromic hypodontia, and the causative gene locus was mapped to chromosome 10q11.2. The aim of this study was to identify potential genetic mutations that could cause He-Zhao deficiency.
Patients with He-Zhao deficiency and their unaffected relatives of the large pedigree were investigated. The whole-exome sequencing using next-generation sequencing was employed to identify genetic variants. The data generated from the whole-exome sequencing using the Illumina Novaseq 6000 system were further analyzed by Burrows-Wheeler Aligner software, Sequence Alignment/Map tools and ANNOVAR tool. In vitro luciferase assay was used to investigate the effect of the detected mutation on gene expression. R environment was used to conduct t-tests. The study protocol was approved by the Research Ethics Committee of Bio-X Institutes, Shanghai Jiao Tong University (M2011004).
The exomes of five patients with He-Zhao deficiency and two of their unaffected relatives identified a mutation in PRKG1α as the molecular etiology of the disease. The variant c.-144 C>A of PRKG1 isoform 1 cosegregated with permanent tooth agenesis in 93 family members who were older than 12, at which time the primary teeth should have been replaced with permanent teeth. Functional studies suggested that the mutant allele promotes gene transcription by increasing its promoter activity.
c.-144 C>A variant of PRKG1α involving odontoclast-associated root resorption is responsible for He-Zhao deficiency, unlike other forms of hypodontia, which typically involve odontoblast dysfunction.
This study aimed to investigate the association between single-nucleotide polymorphisms (SNPs) of PCSK1 (proprotein convertase subtilisin/kexin type 1) related to obesity and nonalcoholic fatty liver disease (NAFLD).
In this case-control observational study, four candidate SNPs (rs6234, rs155971, rs6232, rs3811951) of PCSK1 were genotyped in 732 NAFLD patients and 823 healthy control participants, all of whom were of ethnic Han Chinese descent. All participants came from Shanghai, China, and joined our study during 2015 to 2016. The frequencies of each allele and genotype, paired linkage disequilibrium, and haplotype were calculated on the SHEsis platform. In addition to SHEsis, five different genetic models (codominant, dominant, recessive, overdominant, and log-additive) were employed to identify the correlation between genotype frequency and NAFLD. This study was approved by the Medical Ethics Committee of Shanghai University of Traditional Chinese Medicine (approved No. 2017LCSY069).
In a comparison of NAFLD patients and healthy participants, none of the four PCSK1 SNPs were significantly correlated with the occurrence of NAFLD (P>0.05), in either genotypic or allelic distribution. The recessive model of rs3811951 appeared to show a correlation (odds ratio=1.077; 95% confidence interval=0.924-1.256; P=0.04), but there was no statistical significance after Bonferroni correction (Pcorr>0.0125).
Four obesity-related PCSK1 SNPs (rs6234, rs155971, rs6232, rs3811951) showed no significant correlation with the development of NAFLD in a Han Chinese population.
The majority of non-small cell lung cancer (NSCLC) cases remain undiagnosed until advanced stages of the disease. Accumulating studies have highlighted the utility of palliative care as an effective treatment option, which relieves patients’ suffering by activating placebo effect in the body. To evaluate the clinical significance of palliative care, data from NSCLC drug-randomized controlled trials (RCTs) were collected and the effects of placebo treatment examined.
PubMed (MEDLINE), Scopus, Web of Science, and China National Knowledge Infrastructure databases were searched from January 1,1978 to September 1,2020. Placebo-controlled phase II/III pharmaceutical RCTs enrolling patients with solely stage III/IV NSCLC were included. The quality of included studies was assessed using the Jadad method. Single-arm and two-arm meta-analyses of the therapeutic and adverse effects of placebo, that is, the primary and secondary outcome measures, were subsequently performed using either Bayesian or conventional models.
Five RCTs including 2245 drug-treated and 1510 placebo-treated patients at NSCLC stage III or IV were included for the study. Low risk of bias was observed for all five included studies using the Cochrane method. Following placebo treatment, controlled disease rate of 24.1% (95% credible interval [CrI], -0.126-0.609) and dropout rate of 2.1% (95% CrI, 0.007-0.039) were calculated, with a dose reduction rate of 3.0% (95% CrI, 0.017-0.045). Compared with active drug treatment, the placebo treatment group had a risk ratio of 0.81 (95% confidence interval, 0.68-0.97) and 0.85 (95% confidence interval, 0.76-0.96) for the achievement of progression-free survival and overall survival, respectively.
In NSCLC drug RCTs, placebo treatment is indicated to generally induce low toxicity in patients by dropout and dose reduction rates and adverse events, although the therapeutic responses could not be precisely determined. The results suggest that under specific circumstances, palliative care which can activate placebo effect may have similar effects as active drugs (such as erlotinib, vandetanib, or pemetrexed) in terms of prolonging survival time.
在题为“体内代谢检测2H-摄入后掺入2H2O”(DOI 10.1097/JBR.0000000000000121)，[
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