Search

Abstract Aim Cannabinoid receptors are components of the endocannabinoid system that affect various physiological functions. We aim to investigate the effect of cannabinoid receptor modulation on kidney disease. Methods PubMed, Web of Science databases, and EMBASE were searched. Articles selection, data extraction and quality assessment were independently performed by two investigators. The SYRCLE’s RoB tool was used to assess the risk of study bias, and pooled SMD using a random-effect model and 95% CIs were calculated. Subgroup analyses were conducted in preselected subgroups, and publication bias was evaluated. We compared the effects of CB1 and CB2 antagonists and/or knockout and agonists and/or genetic regulation on renal function, blood glucose levels, body weight, and pathological damage-related indicators in different models of chronic and acute kidney injury. Results The blockade or knockout of CB1 could significantly reduce blood urea nitrogen [SMD,− 1.67 (95% CI − 2.27 to − 1.07)], serum creatinine [SMD, − 1.88 (95% CI − 2.91 to − 0.85)], and albuminuria [SMD, − 1.60 (95% CI − 2.16 to − 1.04)] in renal dysfunction animals compared with the control group. The activation of CB2 group could significantly reduce serum creatinine [SMD, − 0.97 (95% CI − 1.83 to − 0.11)] and albuminuria [SMD, − 2.43 (95% CI − 4.63 to − 0.23)] in renal dysfunction animals compared with the control group. Conclusions The results suggest that targeting cannabinoid receptors, particularly CB1 antagonists and CB2 agonists, can improve kidney function and reduce inflammatory responses, exerting a renal protective effect and maintaining therapeutic potential in various types of kidney disease.

Abstract Background RNA methylation is a widely known post-transcriptional regulation which exists in many cancer and immune system diseases. However, the potential role and crosstalk of five types RNA methylation regulators in diabetic nephropathy (DN) and immune microenvironment remain unclear. Methods The mRNA expression of 37 RNA modification regulators and RNA modification regulators related genes were identified in 112 samples from 5 Gene Expression Omnibus datasets. Nonnegative Matrix Factorization clustering method was performed to determine RNA modification patterns. The ssGSEA algorithms and the expression of human leukocyte antigen were employed to assess the immune microenvironment characteristics. Risk model based on differentially expression genes responsible for the modification regulators was constructed to evaluate its predictive capability in DN patients. Furthermore, the results were validated by using immunofluorescence co-localizations and protein experiments in vitro. Results We found 24 RNA methylation regulators were significant differently expressed in glomeruli in DN group compared with control group. Four methylation-related genes and six RNA regulators were introduced into riskScore model using univariate Logistic regression and integrated LASSO regression, which could precisely distinguish the DN and healthy individuals. Group with high-risk score was associated with high immune infiltration. Three distinct RNA modification patterns were identified, which has significant differences in immune microenvironment, biological pathway and eGFR. Validation analyses showed the METTL3, ADAR1, DNMT1 were upregulated whereas YTHDC1 was downregulated in DN podocyte cell lines comparing with cells cultured by the normal glucose. Conclusion Our study reveals that RNA methylation regulators and immune infiltration regulation play critical roles in the pathogenesis of DN. The bioinformatic analyses combine with verification in vitro could provide robust evidence for identification of predictive RNA methylation regulators in DN.

Abstract Background Coinfections in patients with coronavirus disease 2019 (COVID-19) affect patient prognosis. Patients with hematologic malignancies (HMs) are usually immunosuppressed and may be at high risk of coinfection, but few related data have been reported. Here, we conducted a retrospective study to explore coinfections in patients with HMs and COVID-19 by next-generation sequencing (NGS) of bronchoalveolar lavage fluid (BALF). Methods The data of hospitalized patients with pneumonia who underwent NGS analysis of BALF were reviewed. COVID-19 patients with HMs were enrolled in the HM group, and those without HMs were enrolled in the non-HM group. The coinfections of the two groups identified by NGS were analyzed. Results Fifteen patients were enrolled in the HM group, and 14 patients were enrolled in the non-HM group. The coinfection rates in the HM group and non-HM group were 80.0% and 85.7%, respectively. The percentage of coinfected bacteria in the HM group was significantly lower than that in the non-HM group (20.0% vs 71.4%, p = 0.005). The coinfection rates of fungi and viruses were 60.0% and 35.7%, respectively, in the HM group and 35.7% and 78.6%, respectively, in the non-HM group, with no significant differences. The most common coexisting pathogen in patients with HMs was Pneumocystis jirovecii (33.3%), and the most common coexisting pathogen in patients without HMs was human gammaherpesvirus 4 (50%). Coinfection with herpesviruses occurred frequently in both groups. Conclusions Our study showed that the majority of hospitalized patients with COVID-19 are likely to be co-infected with other pathogens. Pneumocystis jiroveci and herpesvirus are commonly coinfected pathogens in patients with HMs. Bacterial coinfection is rare in patients with HMs but is more common in patients without HMs.

Abstract Background Patients treated with anti-CD20 monoclonal antibodies could have a higher risk of adverse outcomes of coronavirus disease 2019 (COVID-19). The novel anti-CD20 monoclonal antibody obinutuzumab has shown greater B-cell depletion and superior in vitro efficacy than rituximab. We aimed to assess whether obinutuzumab would result in worse COVID-19 outcomes than rituximab. Methods We retrospectively reviewed 124 patients with B-cell lymphoma, 106 of whom received rituximab treatment and 18 of whom received obinutuzumab treatment. The adverse outcomes of COVID-19 were compared between patients in the two cohorts. Results The proportions of patients who were hospitalized (55.6% vs. 20.8%, p = 0.005), experienced prolonged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (38.9% vs. 2.9%, p

Abstract Background Previous studies indicated that excessive engagement in digital devices could lead to negative psychological impacts in general population. We aimed to determine the association of electronic screen exposure with depression among women in early pregnancy. Methods A cross-sectional study was conducted from June 2021 to June 2022. A total of 665 women in early pregnancy were recruited and the information included socio-demographic characteristics, screen exposure and Patient Health Questionnaire − 9 depression scale. Results Among the women in early pregnancy, the total daily smartphone viewing time was the longest (median [P25-P75], 5 [3–6] hours/day) in the three types of electronic screen exposure. The total daily smartphone viewing time (P = 0.015, OR[95%CI] = 1.09[1.11–1.18]), smartphone (P = 0.016, OR[95%CI] = 1.24[1.04–1.47]) and television viewing time (P = 0.006, OR[95%CI] = 1.35[1.09–1.67]) before nocturnal sleep were significantly associated with depression among women in early pregnancy. The thresholds calculated by receiver operator characteristic curves were 7.5 h/day, 1.5 h/day and 1.5 h/day, respectively. In addition, women with higher scores of smartphone addiction were more susceptible to depression (P

Abstract Background We previously conducted a case-control study and found that exposure to electronic screen before nocturnal sleep was associated with hypertensive disorders in pregnancy (HDP). Hence, we carried out this cohort study aiming to identify the effects of screen exposure time on the incidence rate and severity of HDP. Methods A retrospective cohort study was conducted from January 2022 and July 2022 from three hospitals in Wuxi and Changzhou cities. A total of 732 women were recruited and the information included socio-demographic characteristics, screen exposure and outcomes. Generalized estimating equations and binary non-conditional logistic models were applied to multivariate analysis, calculating the odds ratios (ORs) and 95% confidence intervals (CIs) of screen exposure time. Results The duration order of total screen time was smartphone > computer > television, while the duration order of screen time before nocturnal sleep was smartphone > television > computer. Multivariate analyses showed that the susceptibility of HDP among women who exposed to television before nocturnal sleep was 81.5% percent higher than those not exposed (P = 0.018, OR[95%CI] = 1.815[1.106–2.981]). In addition, total daily exposure time of television in the third trimester of pregnancy significantly increased the severity of HDP (P = 0.021, OR[95%CI] = 3.641[1.213–10.927]). Conclusions Based on this preliminary study, we would suggest that pregnant women do not watch television before nocturnal sleep. While in the third trimester of pregnancy, total exposure time of television should be limited. Investigations from other areas and experimental studies should be conducted to verify the conclusion.

Abstract Botrytis cinerea is the causative agent of gray mold, a fungal disease affecting a broad array of food crops and resulting in considerable agricultural and economic losses. Currently, chemical fungicides are the most effective control measure, but this practice is challenged by the growing resistance of pathogens to these fungicides. Scopoletin, a major phytoalexin of tobacco plants, has shown promise as an antifungal treatment. Here, we found that scopoletin was effective against B. cinerea infection of tomato leaves. It inhibited mycelial growth and conidial germination of B. cinerea and disrupted cell wall, cell membrane, and infection structure formation. Transcriptomic analysis identified 3495 differentially expressed genes in response to scopoletin treatment. Interestingly, scopoletin seems to deactivate the HOG pathway of B. cinerea. The growth defect caused by hyperactivation of the pathway, such as iprodione treatment and deletion of BcPtc1, the negative regulator of this pathway, was partly rescued by scopoletin. Moreover, it could downregulate phosphorylation levels of BcSak1 treated with iprodione and NaCl. In addition, the control efficiency of triadimefon was significantly increased by scopoletin. Thus, scopoletin is a promising, naturally derived, and sustainable treatment for gray mold, especially when combined with triadimefon.

Abstract Background Previous studies achieved low microbial detection rates in lymphoma patients with interstitial pneumonia (IP) after chemotherapy. However, the metagenomic next-generation sequencing (mNGS) is a comprehensive approach that is expected to improve the pathogen identification rate. Thus far, reports on the use of mNGS in lymphoma patients with chemotherapy-related IP remain scarce. In this study, we summarized the microbial detection outcomes of lymphoma patients with chemotherapy-related IP through mNGS testing of bronchoalveolar lavage fluid (BALF). Methods Fifteen lymphoma patients with chemotherapy-related IP were tested for traditional laboratory microbiology, along with the mNGS of BALF. Then, the results of mNGS and traditional laboratory microbiology were compared. Results Of the 15 enrolled patients, 11 received rituximab and 8 were administered doxorubicin hydrochloride liposome. The overall microbial yield was 93.3% (14/15) for mNGS versus 13.3% (2/15) for traditional culture methods (P ≤ 0.05). The most frequently detected pathogens were Pneumocystis jirovecii (12/15, 80%), Cytomegalovirus (4/15, 26.7%), and Epstein-Barr virus (3/15, 20%). Mixed infections were detected in 10 cases. Five patients recovered after the treatment with antibiotics alone without glucocorticoids. Conclusion Our findings obtained through mNGS testing of BALF suggested a high microbial detection rate in lymphoma patients with IP after chemotherapy. Notably, there was an especially high detection rate of Pneumocystis jirovecii. The application of mNGS in patients with chemotherapy-related IP was more sensitive.

Abstract Background The RNA profiles of tumor-educated platelets (TEPs) possess pathological features that could be used for early cancer detection. However, the utility of TEP RNA profiling in detecting early colorectal cancer (CRC) versus noncancerous colorectal diseases has not yet been investigated. This study assesses the diagnostic capacity of TEP RNA profiles in a cohort of patients with CRC and noncancerous diseases. Methods Transcriptome sequencing for platelets isolated from 132 patients with CRC at early and late stages and 190 controls consisting of healthy donors and patients with ulcerative disease, Crohn’s disease, polyps, and adenomas was performed and analyzed using binary particle swarm optimization coupled with support vector machine to identify genes that contributed to the classification of CRC patients versus controls. The area under the receiver operating curves (AUROCs) and the accuracy of TEP RNA profiles in CRC diagnosis were assessed. Results TEP RNA profiling achieved high performance in distinguishing and staging CRC patients from the controls. Using the swarm intelligence algorithm, the 921 most contributive genes that classified CRC patients from the controls were identified. AUROCs of 0.928 for the training set via leave-one-out cross-validation and 0.92 for the validation set were achieved, both of which were significantly higher than the clinically utilized serum biomarkers: carcinoembryonic antigen and cancer antigen 19-9. Notably, an AUROC of 0.915 in an external validation set was achieved. For predicting different CRC stages, an AUROC of 0.984 was achieved in the training set and 1.000 in the internal validation set. Conclusions RNA profiles of TEPs are of potential diagnostic value for identifying early CRC from noncancerous diseases. Prospective studies are needed to validate its clinical relevance.

Abstract Background A single circular mitochondrial (mt) genome is a common feature across most metazoans. The mt-genome includes protein-coding genes involved in oxidative phosphorylation, as well as RNAs necessary for translation of mt-RNAs, whose order and number are highly conserved across animal clades, with few known exceptions of alternative mt-gene order or mt-genome architectures. One such exception consists of the fragmented mitochondrial genome, a type of genome architecture where mt-genes are split across two or more mt-chromosomes. However, the origins of mt-genome fragmentation and its effects on mt-genome evolution are unknown. Here, we investigate these origin and potential mechanisms underlying mt-genome fragmentation, focusing on a genus of booklice, Liposcelis, which exhibits elevated sequence divergence, frequent rearrangement of mt-gene order, and fragmentation of the mt genome, and compare them to other Metazoan clades. Results We found this genus Liposcelis exhibits very low conservation of mt-gene order across species, relative to other metazoans. Levels of gene order rearrangement were, however, unrelated to whether or not mt-genomes were fragmented or intact, suggesting mitochondrial genome fragmentation is not affecting mt-gene order directly. We further investigated possible mechanisms underpinning these patterns and revealed very high conservation of non-coding sequences at the edges of multiple recombination regions across populations of one particular Liposcelis species, supportive of a hypothesis that mt-fragmentation arises from recombination errors between mt-genome copies. We propose these errors may arise as a consequence of a heightened mutation rate in clades exhibiting mt-fragmentation. Consistent with this, we observed a striking pattern across three Metazoan phyla (Arthropoda, Nematoda, Cnidaria) characterised by members exhibiting high levels of mt-gene order rearrangement and cases of mt-fragmentation, whereby the mt-genomes of species more closely related to species with fragmented mt-genomes diverge more rapidly despite experiencing strong purifying selection. Conclusions We showed that contrary to expectations, mt-genome fragmentation is not correlated with the increase in mt-genome rearrangements. Furthermore, we present evidence that fragmentation of the mt-genome may be part of a general relaxation of a natural selection on the mt-genome, thus providing new insights into the origins of mt-genome fragmentation and evolution.

Abstract Background Silk glands are used by silkworms to spin silk fibers for making their cocoons. These have recently been regarded as bioreactor hosts for the cost-effective production of other valuable exogenous proteins and have drawn wide attention. Results In this study, we established a transgenic silkworm strain which synthesizes the recombinant human lactoferrin (rhLF) in the silk gland and spins them into the cocoon by our previously constructed silk gland based bioreactor system. The yield of the rhLF with the highest expression level was estimated to be 12.07 mg/g cocoon shell weight produced by the transgenic silkworm strain 34. Utilizing a simple purification protocol, 9.24 mg of the rhLF with recovery of 76.55% and purity of 95.45% on average could be purified from 1 g of the cocoons. The purified rhLF was detected with a secondary structure similar with the commercially purchased human lactoferrin. Eight types of N-glycans which dominated by the GlcNAc (4) Man (3) (61.15%) and the GlcNAc (3) Man (3) (17.98%) were identified at the three typical N-glycosylation sites of the rhLF. Biological activities assays showed the significant evidence that the purified rhLF could relief the lipopolysaccharide (LPS)-induced cell inflammation in RAW264.7 cells and exhibit potent antibacterial bioactivities against the Escherichia coli (E. coli) and Bacillus subtilis. Conclusions These results show that the middle silk gland of silkworm can be an efficient bioreactor for the mass production of rhLF and the potential application in anti-inflammation and antibacterial.