The Effect of Placebo on Pruritus in Patients with Chronic Urticaria: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials.

BACKGROUND: The anti-pruritic effect of placebo in patients with chronic urticaria has gained increasing attention in clinical research. However, the extent of placebo effect and its influencing factors in the treatment of chronic urticaria are not well understood. OBJECTIVE: The objective of this systematic review and meta-analysis was to investigate the effect of placebo on pruritus in patients with chronic urticaria and to explore relevant influencing factors. METHODS: PubMed, Embase, Web of Science, Cochrane Library, and PsycINFO were searched from inception to 10 July, 2024. Primary outcome included pruritus scores. The secondary outcomes focused on global symptoms and quality of life. Subgroup analyses and meta-regression analyses were conducted based on drug types, sample size, participants' age, and other variables. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system and a trial sequential analysis were employed to establish the reliability of evidence. RESULTS: A total of 65 eligible publications (including 67 randomized controlled trials) involving 10,704 patients with chronic urticaria were included. The pruritus scores decreased following placebo treatment (moderate evidence). In addition, favorable results were observed in global symptoms (moderate evidence) and quality of life (low evidence) after placebo treatment. Subgroup analyses indicated that the type of active medication in intervention groups was an influencing factor of placebo effect of pruritus. Meta-regression analyses demonstrated that the anti-pruritic effect of placebo was inversely correlated with sample size and positively correlated with participants' age. A trial sequential analysis provided further support for the anti-pruritic effect of placebo. CONCLUSIONS: A substantial improvement of pruritus after placebo treatment was observed in patients with chronic urticaria. The anti-pruritic effect of placebo varied with sample size, participants' age, and type of active medication used. Future research should further investigate the effect size of placebo and clarify the potential mechanism. PROSPERO REGISTRATION: The protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) as CRD42023482608.

Neohesperidin Attenuates DSS-Induced Ulcerative Colitis by Inhibiting Inflammation, Reducing Intestinal Barrier Damage, and Modulating Intestinal Flora Composition.

Flavonoid natural products are emerging as a promising approach for treating Ulcerative Colitis (UC) due to their natural origin and minimal toxicity. This study investigates the effects of Neohesperidin (NEO), a natural flavonoid, on Dextran Sodium Sulfate (DSS)-induced UC in mice, focusing on the underlying molecular mechanisms. Early intervention with NEO (25 and 50 mg/kg) mitigated colon shortening, restored damaged barrier proteins, and significantly reduced the inflammatory cytokine levels. Moreover, NEO inhibited the MAPK/NF-κB signaling pathway and enhanced the levels of intestinal barrier proteins (Claudin-3 and ZO-1). Additionally, NEO increased beneficial intestinal probiotics (S24-7 and Lactobacillaceae) while reducing harmful bacteria (Erysipelotrichi, Enterobacteriaceae). Fecal microbial transplantation (FMT) results demonstrated that NEO (50 mg/kg) markedly improved UC symptoms. In conclusion, early NEO intervention may alleviate DSS-induced UC by inhibiting inflammatory responses, preserving intestinal barrier integrity and modulating gut microbiota.

Tricyclic Benzo[1,3]oxazinyloxazolidinones as Potent Antibacterial Agents against Drug-Resistant Pathogens.

Herein, we developed a series of benzo[1,3]oxazinyloxazolidinones as potent antibacterial agents. Some of the compounds exhibited potent antibacterial activity against a range of clinical drug-resistant pathogens, including Mtb, MRSA, MRSE, VISA, and VRE. Notably, compound 16d inhibited protein synthesis and displayed potent activity against linezolid-resistant Enterococcus faecalis. Although 16d showed cross-resistance to linezolid-resistant MRSA, the frequency of resistance development of MRSA against 16d was lower compared to that of linezolid. Additionally, 16d exhibited excellent pharmacokinetic properties and superior in vivo efficacy compared to linezolid. Furthermore, compound 16d modulated cytokine levels and ameliorated histopathological changes in major organs of bacterially infected mice. Hoechst-PI double staining and scanning electron microscopy analyses revealed that 16d exhibited some similarities with linezolid in its effects while also demonstrating a distinct mechanism characterized by cell membrane damage. Moreover, 16d significantly disrupted the MRSA biofilms. The antibacterial agent 16d represents a promising candidate for the treatment of serious infections caused by drug-resistant bacteria.

Novel analgesic peptide derived from Cinobufacini injection suppressing inflammation and pain via ERK1/2/COX-2 pathway.

Inflammatory pain is a chronic pain caused by peripheral tissue inflammation, seriously impacting the patient's life quality. Cinobufacini injection, as a traditional Chinese medicine injection preparation, shows excellent efficacy in anti-inflammatory and analgesic treatment in patients with advanced tumors. In this study, a novel analgesic peptide CI5 with anti-inflammatory and analgesic bio-functions that naturally presents in Cinobufacini injection and its regulatory mechanism are reported. Our results showed that the administration of CI5 significantly relieved the pain of mice in the acetic acid twisting analgesic model and formalin inflammatory pain model. Furthermore, CI5 effectively reduced the inflammatory cytokines (IL-6, TNF-α and IL-1ß) and inflammatory mediator (PGE2) expressions, and prevented the carrageenan-induced paw edema in mice. Further LC-MS/MS results showed the anti-inflammatory and analgesic bio-functions of CI5 depended on its interaction with the Rac-2 protein upstream of ERK1/2 and the inflammatory signaling pathway (ERK1/2/COX-2 axis). In summary, CI5, as a novel natural candidate identified from Cinobufacini injection, showed substantial clinical promise for inflammatory pain treatments.

Exploring the Bidirectional Effects of Gut Microbiota and Short-Chain Fatty Acids on Urticaria Subtypes Through Mendelian Randomization and Mediation Analysis.

Background: Emerging evidence links gut microbiota and their by-products, notably short-chain fatty acids (SCFAs), to urticaria. This study employs multiple Mendelian Randomization (MR) analyses to unravel the complex interactions among gut microbiota, SCFAs, and different subtypes of urticaria, aiming to elucidate the underlying mechanisms and enhance future clinical research. Methods: We analyzed published genome-wide association study (GWAS) summary statistics to identify associations between gut microbiota and three common subtypes of urticaria: spontaneous, dermatographic, and temperature-triggered. Initial two-sample and reverse MR analyses explored the causality in these relationships. Subsequent multivariate MR analyses investigated the role of SCFAs in modulating these interactions, with multiple sensitivity analyses to ensure robustness. Findings: Specific taxa were differently associated with various urticaria subtypes. From microbiota to urticaria: one taxon was negatively associated with dermatographic urticaria; seven taxa were negatively associated and four positively associated with temperature-triggered urticaria; four taxa were negatively associated and six positively associated with spontaneous urticaria. Conversely, from urticaria to microbiota: five taxa were negatively associated with dermatographic urticaria; four were negatively and two positively associated with temperature-triggered urticaria; and two were negatively associated with spontaneous urticaria. These associations were observed at a nominal significance level (P < 0.05). After applying Bonferroni correction for multiple testing, these associations did not reach statistical significance. The observed trends, however, provide insights into potential microbiota-urticaria interactions. Multivariate MR analyses elucidated the role of SCFAs, particularly acetate, which plays a crucial role in modulating immune response. Adjusting for acetate revealed direct effects of Actinobacteria, Bifidobacteriales, and Bifidobacteriaceae on spontaneous urticaria, with corresponding mediation effects of -22%, -24.9%, and -24.9% respectively. Similarly, adjustments for Alcaligenaceae and Betaproteobacteria indicated significant negative effects of acetate on dermatographic and spontaneous urticaria, with mediation effects of -21.7% and -23.7%, respectively. Conclusion: This study confirms the interconnected roles of gut microbiota, SCFAs, and urticaria. It highlights SCFAs' potential mediating role in influencing urticaria through microbiota, providing insights for future therapeutic strategies.

Reliability and validity of "My Jump 2" application for countermovement jump free arm and interlimb jump symmetry in different sports of professional athletes.

Background: Vertical jumping is an important evaluation tool to measure muscle strength and power as well as lower limb symmetry. It is of practical importance and value to develop and utilize a portable and low-cost mobile application (APP) to evaluate jumping. The "My Jump 2" app is an iPhone camera-based application for measuring jumping movements, which is applied to the countermovement jump (CMJ) vertical jumps of the lower limbs of athletes in different sports. The validity of this application and previous versions applied to different forms of vertical jump tests has been preliminarily demonstrated in different population, which has an obvious progress in research. Therefore, the reliability and validity of the jump height, time of flight parameters and symmetry of the CMJ vertical jump of athletes in different sports are needed to be verified by more experiments. Purpose: The purpose of this study is to verify whether "My Jump 2" can effectively and reliably assess jump height, flight practice and lower limb symmetry in CMJAM (countermovement jump free arm) tests in fencing, swimming and diving athletes. Methods: Seventy-nine fencers, swimmers and divers with training experience participated in this study. They completed a total of three CMJAM vertical jump and lower limb symmetry tests in 1 day, while being assessed by using the "My Jump 2" application and a force platform. The intra-group correlation coefficient (ICC) was used to verify reliability, while the Cronbach's alpha and coefficient of variation (CV%) was used to analyze the stability of the CMJAM vertical jump test over three jumps. The Pearson correlation coefficient was used to verify the strength of the relationship between methods (i.e., concurrent validity), and the Bland-Altman plot was used to represent consistency, meanwhile, the t-test was used to determine the systematic bias between methods. Results: Compared with the force platform, the cumulative height values of the total number of jumps (r = 0.999; p = 0.000), the cumulative time to vacate (r = 0.999; p = 0.000) for the CMJAM test obtained by the "My Jump 2" application, the height (ICC = 0.999-1, p = 0.000), the time to vacate flight (ICC = 0.999-1, p = 0.000), contact time symmetry (ICC = 0.976-0.994, p = 0.000), and flight time symmetry (ICC = 0.921-0.982, p = 0.000), respectively. Showed high correlation between the results of "my jump 2" app and the force platform. Conclusion: The "My Jump 2" application is a valid tool to assess CMJAM vertical jump and lower limb symmetry in fencing, swimming and diving athletes with training experience.

Genetic causality and metabolite pathway identifying the relationship of blood metabolites and psoriasis.

BACKGROUND: Psoriasis is a chronic inflammatory disease that causes significant disability. However, little is known about the underlying metabolic mechanisms of psoriasis. Our study aims to investigate the causality of 975 blood metabolites with the risk of psoriasis. MATERIALS AND METHODS: We mainly applied genetic analysis to explore the possible associations between 975 blood metabolites and psoriasis. The inverse variance weighted (IVW) method was used as the primary analysis to assess the possible association of blood metabolites with psoriasis. Moreover, generalized summary-data-based Mendelian randomization (GSMR) was used as a supplementary analysis. In addition, linkage disequilibrium score regression (LDSC) was used to investigate their genetic correction further. Metabolic pathway analysis of the most suggested metabolites was also performed using MetaboAnalyst 5.0. RESULTS: In our primary analysis, 17 metabolites, including unsaturated fatty acids, phospholipids, and triglycerides traits, were selected as potential factors in psoriasis, with odd ratios (OR) ranging from 0.986 to 1.01. The GSMR method confirmed the above results (ß = 0.001, p < 0.05). LDSC analysis mainly suggested the genetic correlation of psoriasis with genetic correlations (rg) from 0.088 to 0.155. Based on the selected metabolites, metabolic pathway analysis suggested seven metabolic pathways including ketone body that may be prominent pathways for metabolites in psoriasis. CONCLUSION: Our study supports the causal role of unsaturated fatty acid properties and lipid traits with psoriasis. These properties may be regulated by the ketone body metabolic pathway.

Action Programmed Nanoantibiotics with pH-Induced Collapse and Negative-Charged-Surface-Induced Deformation against Antibiotic-Resistant Bacterial Peritonitis.

The incorporation of well-designed antibiotic nanocarriers, along with an antibiotic adjuvant effect, in combination with various antibiotics, offers an opportunity to combat drug-resistant strains. However, precise control over morphology and encapsulated payload release can significantly impact their antibacterial efficacy and synergistic effects when used alongside antibiotics. Here, this study focuses on developing lipopeptide-based nanoantibiotics, which demonstrate an antibiotic adjuvant effect by inducing pH-induced collapse and negative-charged-surface-induced deformation. This enhances the disruption of the bacterial outer membrane and facilitates drug penetration, effectively boosting the antimicrobial activity against drug-resistant strains. The modulation regulations of the lipopeptide nanocarriers with modular design are governed by the authors. The nanoantibiotics, made from lipopeptide and ciprofloxacin (Cip), have a drug loading efficiency of over 80%. The combination with Cip results in a significantly low fractional inhibitory concentration index of 0.375 and a remarkable reduction in the minimum inhibitory concentration of Cip against multidrug-resistant (MDR) Escherichia coli (clinical isolated strains) by up to 32-fold. The survival rate of MDR E. coli peritonitis treated with nanoantibiotics is significantly higher, reaching over 87%, compared to only 25% for Cip and no survival for the control group. Meanwhile, the nanoantibiotic shows no obvious toxicity to major organs.

Effect and mechanism of natural composite hydrogel from fish scale intercellular matrix on diabetic chronic wound repair.

Diabetes mellitus is a chronic metabolic disease with prolonged low-grade inflammation and impaired cellular function, leading to poor wound healing. The treatment of diabetic wounds remains challenging due to the complex wound microenvironment. In view of the prominence of fish scales in traditional Chinese medicine and their wide application in modern medicine, we isolated the intercellular components in the scales of sea bass, obtained a natural composite hydrogel, fish scales gel (FSG), and applied it to diabetic chronic wounds. FSG was rich in collagen-like proteins, and possessed low-temperature gelation properties. In vitro, FSG was biocompatible and promoted fibroblast proliferation by approximately 40 %, endothelial cell migration by approximately 20 % and activated the M1 macrophages. In addition, FSG restored the function of fibroblasts and vascular endothelial cells damaged by high glucose. Importantly, FSG normalized the acute inflammatory response to impaired macrophages in a high-glucose microenvironment. Transcriptome analysis implies that this mechanism may involve enhanced cell signaling and cellular communication, improved sensitivity to cytokines, and activation of the TNF signaling pathway. Animal experiments confirmed that FSG significantly improved wound closure by approximately 15 % in diabetic rats, showing similar effects to acute wounds. In conclusion, the regulation of multiple cellular functions by FSG, especially the counterintuitive ability to induce acute inflammation, promoted diabetic wound healing and provides a novel therapeutic strategy for wound repair in diabetic patients.

Arbutin alleviates intestinal colitis by regulating neutrophil extracellular traps formation and microbiota composition.

BACKGROUND: Ulcerative colitis (UC) is a chronic recurrent intestinal disease lacking effective treatments. ß-arbutin, a glycoside extracted from the Arctostaphylos uva-ursi leaves, that can regulate many pathological processes. However, the effects of ß-arbutin on UC remain unknown. PURPOSE: In this study, we investigated the role of ß-arbutin in relieving colitis and explored its potential mechanisms in a mouse model of dextran sulfate sodium (DSS)-induced colitis. METHODS: In C75BL/6 J mice, DSS was used to induce colitis and concomitantly ß-arbutin (50 and 100 mg/kg) was taken orally to evaluate its curative effect by evaluating disease activity index (DAI) score, colon length and histopathology. Alcian blue periodic acid schiff (AB-PAS) staining, immunohistochemistry (IHC), immunofluorescence (IF) and TdT-mediated dUTP Nick-End Labeling (Tunel) staining were used to assess intestinal barrier function. Flow cytometry, double-IF and western blotting (WB) were performed to verify the regulatory mechanism of ß-arbutin on neutrophil extracellular traps (NETs) in vivo and in vitro. NETs depletion experiments were used to demonstrate the role of NETs in UC. Subsequently, the 16S rRNA gene sequencing was used to analyze the intestinal microflora of mouse. RESULTS: Our results showed that ß-arbutin can protect mice from DSS-induced colitis characterized by a lower DAI score and intestinal pathological damage. ß-arbutin reduced inflammatory factors secretion, notably regulated neutrophil functions, and inhibited NETs formation in an ErK-dependent pathway, contributing to the resistance to colitis as demonstrated by in vivo and in vitro experiments. Meanwhile, remodeled the intestinal flora structure and increased the diversity and richness of intestinal microbiota, especially the abundance of probiotics and butyric acid-producing bacteria. It further promoted the protective effect in the resistance of colitis. CONCLUSION: ß-arbutin promoted the maintenance of intestinal homeostasis by inhibiting NETs formation, maintaining mucosal-barrier integrity, and shaping gut-microbiota composition, thereby alleviating DSS-induced colitis. This study provided a scientific basis for the rational use of ß-arbutin in preventing colitis and other related diseases.

Acupuncture versus tricyclic antidepressants in the prophylactic treatment of tension-type headaches: an indirect treatment comparison meta-analysis.

BACKGROUND: Acupuncture showed better improvement than sham acupuncture in reducing attack frequency of tension-type headache (TTH), but its effectiveness relative to first-line drugs for TTH is unknown, which impedes the recommendation of acupuncture for patients who are intolerant to drugs for TTH. We aimed to estimate the relative effectiveness between acupuncture and tricyclic antidepressants (TCAs) through indirect treatment comparison (ITC) meta-analysis. METHODS: We searched Ovid Medline, Embase, and Cochrane Library from database inception until April 13, 2023. Randomized controlled trials of TCAs or acupuncture in the prevention of TTH in adults were included. The primary outcome was headache frequency. The secondary outcomes were headache intensity, responder rate, and adverse event rate. Bayesian random-effect models were used to perform ITC meta-analysis, and confidence of evidence was evaluated by using the GRADE approach. RESULTS: A total of 34 trials involving 4426 participants were included. Acupuncture had similar effect with TCAs in decreasing TTH frequency (amitriptyline: mean difference [MD] -1.29, 95% CI -5.28 to 3.02; amitriptylinoxide: MD -0.05, 95% CI -6.86 to 7.06) and reducing TTH intensity (amitriptyline: MD 2.35, 95% CI -1.20 to 5.78; clomipramine: MD 1.83, 95% CI -4.23 to 8.20). Amitriptyline had a higher rate of adverse events than acupuncture (OR 4.73, 95% CI 1.42 to 14.23). CONCLUSION: Acupuncture had similar effect as TCAs in reducing headache frequency of TTH, and acupuncture had a lower adverse events rate than amitriptyline, as shown by very low certainty of evidence.

Different doses and courses of omalizumab for patients with chronic spontaneous urticaria: A systematic review with meta-analysis and trial sequential analysis.

Background: The stability, efficacy, and safety of omalizumab at different doses and regimens for chronic spontaneous urticaria (CSU) are yet to be studied. Objective: A systematic review (SR) with meta-analysis (MA) and trial sequential analysis (TSA) was performed to assess the efficacy and safety of omalizumab in CSU. Methods: Randomised controlled trials (RCTs) of administering omalizumab versus placebo for CSU were searched. Random-effects MAs were performed using planned subgroup analyses. TSA was performed to control for the risk of random errors and assess the stability of our MA results. Publication bias was visually assessed using a contour-enhanced funnel plot and the trim-and-fill method. The quality of RCTs was assessed using the Cochrane Risk of Bias Tool 2. Results: Twelve studies met the inclusion criteria. Omalizumab had remarkable effects on the patient percentage of the weekly urticaria activity score is zero (UAS = 0) [RR 4.64, 95% CI (3.38, 6.37)], percentage of no angioedema-burdened days [MD 3.15, 95% CI (0.10, 6.19], patient percentage of UAS ≤6 [RR 3.05, 95% CI (2.46, 3.78)], and patient percentage of the weekly itch severity score minimally important difference (ISS7 MID) [RR 1.50, 95% CI (1.36, 1.66)]. Omalizumab was well tolerated across studies [RR 0.98, 95% CI (0.90, 1.08)]. TSA confirmed the above results, except for "the percentage of no angioedema-burdened day". Conclusion: Among the different doses and courses assessed, omalizumab (300 mg, 12 weeks) can be recommended as an effective treatment for patients with CSU. However, whether omalizumab improves angioedema requires further investigation. The clinical management of angioedema accompanying CSU requires further attention.

An Automated and Fast Sample Preparation Workflow for Laser Microdissection Guided Ultrasensitive Proteomics.

Spatial tissue proteomics integrating whole-slide imaging, laser microdissection, and ultrasensitive mass spectrometry is a powerful approach to link cellular phenotypes to functional proteome states in (patho)physiology. To be applicable to large patient cohorts and low sample input amounts, including single-cell applications, loss-minimized and streamlined end-to-end workflows are key. We here introduce an automated sample preparation protocol for laser microdissected samples utilizing the cellenONE robotic system, which has the capacity to process 192 samples in 3 h. Following laser microdissection collection directly into the proteoCHIP LF 48 or EVO 96 chip, our optimized protocol facilitates lysis, formalin de-crosslinking, and tryptic digest of low-input archival tissue samples. The seamless integration with the Evosep ONE LC system by centrifugation allows 'on-the-fly' sample clean-up, particularly pertinent for laser microdissection workflows. We validate our method in human tonsil archival tissue, where we profile proteomes of spatially-defined B-cell, T-cell, and epithelial microregions of 4000 µm2 to a depth of ∼2000 proteins and with high cell type specificity. We finally provide detailed equipment templates and experimental guidelines for broad accessibility.

Disease-Related Factors Associated with Acupuncture Response in Patients with Chronic Tension-Type Headache: A Secondary Analysis of A Randomized Controlled Trial.

OBJECTIVE: To explore the demographic and disease-related factors associated with acupuncture response in patients with chronic tension-type headache (CTTH). METHODS: Using data from a randomized clinical trial (218 cases) consisting of 4 weeks of baseline assessment, 8 weeks of treatment, and 24 weeks of follow-up, participants were regrouped into responders (at least a 50% reduction in monthly headache days at week 16 compared with baseline) and non-responders. Twenty-three demographic and disease-related factors associated with acupuncture response in 183 participants were analyzed by multivariable logistic regression. RESULTS: One hundred and nineteen (65.0%) participants were classified as responders. Four factors were significantly independently associated with acupuncture response, including treatment assignment, headache intensity at baseline, and 2 domains [general health (GH) and social functioning (SF)] from the 36-Item Short Form Health Survey quality of life questionnaire. Treatment assignment was associated with non-response: participants receiving true acupuncture were 3-time more likely to achieve a CTTH response than those receiving superficial acupuncture [odds ratio (OR) 0.322, 95% confidence interval (CI) 0.162 to 0.625, P=0.001]. Compared with patients with mild-intensity headache, patients with moderate-intensity headache were twice as likely to respond to acupuncture (OR 2.001, 95% CI 1.020 to 4.011, P=0.046). The likelihood of non-response increased by 4.5% with each unit increase in the GH grade (OR 0.955, 95% CI 0.917 to 0.993, P=0.024) while decreased by 3.8% with each unit increase in the SF grade (OR 1.038, 95% CI 1.009 to 1.069, P=0.011). CONCLUSIONS: Greater headache intensity, lower GH score, and higher SF score were associated with better acupuncture responses in CTTH patients. These 3 factors require independent validation as predictors of acupuncture effectiveness in CTTH.

Pharmacological inhibition of ICOS attenuates the protective effect of exercise on cardiac fibrosis induced by isoproterenol.

AIMS: To investigate the cardioprotective mechanism of exercise or exercise combined with inducible costimulatory molecules (ICOS) monoclonal antibody (mAb) therapy against isoproterenol (ISO)-induced cardiac remodeling. MAIN METHODS: Totally 24 male C57BL/6J mice were randomly divided into four groups: the control group (normal saline treatment), ISO group (subcutaneous injection of isoproterenol, 10 mg/kg/day, once daily for 5 consecutive days), the exercise with subcutaneous ISO injection group (EPI), and the exercise with injected with ISO and ICOS mAb group (EPII). The mice in EPI and EPII group were trained on a small animal treadmill for 4 weeks (13 m/min, 0% grade, 60min/day). KEY FINDINGS: Exercise significantly attenuated CD45+, Mac-2 inflammatory cell infiltration, cardiac fibrosis and inhibited the RIPK1/RIPK3/MLKL/CaMKII and cardiomyocyte pyroptosis pathways to counter ISO-induced severe cardiac injury. The administration of the ICOS mAb may inhibit the cardioprotection of exercise against ISO-induced heart damage. Compared to those in EPI, our data showed that the increasing levels of myocardial fibrosis, the leukocyte infiltration of cardiac tissue and proteins expression of cardiac myocyte necrosis and pyroptosis signaling pathways in the EPII group. SIGNIFICANCE: Our results demonstrated that exercise decreased leukocyte infiltration in heart, inhibited the cardiomyocyte pyroptosis and necroptosis signaling pathways, and attenuated inflammatory responses to alleviate ISO-induced cardiac fibrosis. However, the antifibrotic effects of combined treatment with exercise and ICOS mAb intervention did not exhibit synergistic enhancement.

The efficacy and safety of oral microecological agents as add-on therapy for atopic dermatitis: A systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Atopic dermatitis (AD) is a common skin disease that is hard to completely cure in a short time. Guidelines recommend the use of topical corticosteroids (TCS) as first-line anti-inflammatory therapy for AD, but long-term use has significant side effects. Microecological agents (MA), including probiotics, prebiotics and synbiotics, have been widely reported as a potential adjunctive therapy of AD, but whether MA can contribute to AD treatment is currently controversial. Therefore, we conducted a systematic review and meta-analysis to investigate whether MA as an add-on therapy for AD has synergistic and attenuated effects and to further understand the role of MA in clinical interventions for AD. METHODS: We systematically searched Medline, Embase, Web of Science, Cochrane Library and PsycINFO databases up to Apr 11, 2023, and bibliographies were also manually searched, for potentially relevant studies regarding MA as additional therapy of AD. The Cochrane Risk of Bias Tool for assessing risk of bias was used to assess the quality of randomized controlled trials (RCTs). Two reviewers screened studies, extracted data, and evaluated the risk of bias independently. The primary outcomes (SCORAD scores and the number of adverse events) and the secondary outcomes (pruritus scores, the quality of life and the frequency of TCS) were extracted from each article. The data were combined and analyzed to quantify the safety and efficacy of the treatment. R (V4.4.3) software was used for data synthesis. The certainty of the evidence was evaluated with the Grade of Recommendation, Assessment, Development and Evaluation (GRADE) system. We also performed a trial sequential analysis to assess the reliability of the evidence. RESULTS: A total of 21 studies, including 1230 individuals, were identified, 20 of which met the eligibility criteria for the meta-analysis. Our pooled meta-analyses showed that compared with controls, oral MA as an add-on therapy was associated with significantly lower SCORAD scores (MD = -5.30, 95% CI -8.50, -1.55, p < 0.01, I2  = 81%). However, adverse events, pruritus scores, quality of life, and frequency of TCS use showed no significant difference in this meta-analysis study (p > 0.05). CONCLUSIONS: This meta-analysis showed that MA plus TCS could be an effective and safe treatment for patients with AD to relieve relevant symptoms, which might be used as an add-on therapy in the treatment of AD. However, due to the limited number of studies, results should be interpreted with caution. Further studies with a larger sample size are needed to explore the optimal protocol of MA plus TCS.

A framework for ultra-low-input spatial tissue proteomics.

Spatial proteomics combining microscopy-based cell phenotyping with ultrasensitive mass-spectrometry-based proteomics is an emerging and powerful concept to study cell function and heterogeneity in (patho)physiology. However, optimized workflows that preserve morphological information for phenotype discovery and maximize proteome coverage of few or even single cells from laser microdissected tissue are currently lacking. Here, we report a robust and scalable workflow for the proteomic analysis of ultra-low-input archival material. Benchmarking in murine liver resulted in up to 2,000 quantified proteins from single hepatocyte contours and nearly 5,000 proteins from 50-cell regions. Applied to human tonsil, we profiled 146 microregions including T and B lymphocyte niches and quantified cell-type-specific markers, cytokines, and transcription factors. These data also highlighted proteome dynamics within activated germinal centers, illuminating sites undergoing B cell proliferation and somatic hypermutation. This approach has broad implications in biomedicine, including early disease profiling and drug target and biomarker discovery. A record of this paper's transparent peer review process is included in the supplemental information.

Genome-wide association and RNA-seq analyses reveal a potential gene related to linolenic acid in soybean seeds.

Linolenic acid (LA) has poor oxidative stability since it is a polyunsaturated fatty acid. Soybean oil has a high LA content and thus has poor oxidative stability. To identify candidate genes that affect the linolenic acid (LA) content in soybean seeds, a genome-wide association study (GWAS) was performed with 1,060 soybean cultivars collected in China between 2019-2021 and which LA content was measured using matrix-assisted laser desorption/ionization time-of-flight imaging mass spectrometry (MALDI-TOF IMS). A candidate gene, GmWRI14, encoding an APETALA2 (AP2)-type transcription factor, was detected by GWAS in cultivars from all three study years. Multiple sequence alignments showed that GmWRI14 belongs to the plant WRI1 family. The fatty acid contents of different soybean lines were evaluated in transgenic lines with a copy of GmWRI14, control lines without GmWRI14, and the gmwri14 mutant. MALDI-TOF IMS revealed that GmWRI14 transgenic soybeans had a lower LA content with a significant effect on seed size and shape, whereas gmwri14 mutants had a higher LA content. compared to control. The RNA-seq results showed that GmWRI14 suppresses GmFAD3s (GmFAD3B and GmFAD3C) and GmbZIP54 expression in soybean seeds, leading to decreased LA content. Based on the RNA-seq data, yeast one-hybrid (Y1H) and qRT-PCR were performed to confirm the transcriptional regulation of FAD3s by GmWRI14. Our results suggest that FAD3 is indirectly regulated by GmWRI14, representing a new molecular mechanism of fatty acid biosynthesis, in which GmWRI14 regulates LA content in soybean seeds.

Biocontrol of bacterial wilt disease in tomato using Bacillus subtilis strain R31.

Bacterial wilt disease caused by Ralstonia solanacearum is a widespread, severe plant disease. Tomato (Solanum lycopersicum), one of the most important vegetable crops worldwide, is particularly susceptible to this disease. Biological control offers numerous advantages, making it a highly favorable approach for managing bacterial wilt. In this study, the results demonstrate that treatment with the biological control strain Bacillus subtilis R31 significantly reduced the incidence of tomato bacterial wilt. In addition, R31 directly inhibits the growth of R. solanacearum, and lipopeptides play an important role in this effect. The results also show that R31 can stably colonize the rhizosphere soil and root tissues of tomato plants for a long time, reduce the R. solanacearum population in the rhizosphere soil, and alter the microbial community that interacts with R. solanacearum. This study provides an important theoretical basis for elucidating the mechanism of B. subtilis as a biological control agent against bacterial wilt and lays the foundation for the optimization and promotion of other agents such as R31.

Pathogen Profile of Klebsiella variicola, the Causative Agent of Banana Sheath Rot.

Banana (Musa spp.) is an important fruit and food crop worldwide. In recent years, banana sheath rot has become a major problem in banana cultivation, causing plant death and substantial economic losses. Nevertheless, the pathogen profile of this disease has not been fully characterized. Klebsiella variicola is a versatile bacterium capable of colonizing different hosts, such as plants, humans, insects, and animals, and is recognized as an emerging pathogen in various hosts. In this study, we obtained 12 bacterial isolates from 12 different banana samples showing banana sheath rot in Guangdong and Guangxi Provinces, China. Phylogenetic analysis based on 16S rRNA sequences confirmed that all 12 isolates were K. variicola strains. We sequenced the genomes of these strains, performed comparative genomic analysis with other sequenced K. variicola strains, and found a lack of consistency in accessory gene content among these K. variicola strains. However, prediction based on the pan-genome of K. variicola revealed 22 unique virulence factors carried by the 12 pathogenic K. variicola isolates. Microbiome and microbial interaction network analysis of endophytes between the healthy tissues of diseased plants and healthy plants of two cultivars showed that Methanobacterium negatively interacts with Klebsiella in banana plants and that Herbaspirillum might indirectly inhibit Methanobacterium to promote Klebsiella growth. These results suggest that banana sheath rot is caused by the imbalance of plant endophytes and opportunistic pathogenic bacteria, providing an important basis for research and control of this disease.[Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.