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MSphere Jun 2024Bacterial ribonuclease E (RNase E) is vital for posttranscriptional regulation by degrading and processing RNA. The RraA protein inhibits RNase E activity through...
Bacterial ribonuclease E (RNase E) is vital for posttranscriptional regulation by degrading and processing RNA. The RraA protein inhibits RNase E activity through protein-protein interactions, exerting a global regulatory effect on gene expression. However, the specific role of RraA remains unclear. In this study, we investigated expression in ZJ-T and identified three promoters responsible for its expression, resulting in transcripts with varying 5'-UTR lengths. During the stationary phase, was significantly posttranscriptionally inhibited. Deletion of had no impact on bacterial growth in rich medium Luria-Bertani broth with salt (LBS) but resulted in decreased biofilm formation and increased resistance to polymyxin B. Transcriptome analysis revealed 350 differentially expressed genes (DEGs) between the wild type and the mutant, while proteome analysis identified 267 differentially expressed proteins (DEPs). Integrative analysis identified 55 genes common to both DEGs and DEPs, suggesting that RraA primarily affects gene expression at the posttranscriptional level. KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis demonstrated that RraA facilitates the conversion of fatty acids, propionic acid, and branched-chain amino acids to acetyl-CoA while enhancing amino acid and peptide uptake. Notably, RraA positively regulates the expression of virulence-associated genes, including those involved in biofilm formation and the type VI secretion system. This study expands the understanding of the regulatory network of RraA through transcriptome analysis, emphasizing the importance of proteomic analysis in investigating posttranscriptional regulation.IMPORTANCERraA is an inhibitor protein of ribonuclease E that interacts with and suppresses its endonucleolytic activity, thereby playing a widespread regulatory role in the degradation and maturation of diverse mRNAs and noncoding small RNAs. However, the physiological functions and associated regulon of RraA in have not been fully elucidated. Here, we report that RraA impacts virulence-associated physiological processes, namely, antibiotic resistance and biofilm formation, in . By conducting an integrative analysis of both the transcriptome and proteome, we revealed the involvement of RraA in carbon metabolism, amino acid catabolism, and transport, as well as in the type VI secretion system. Collectively, these findings elucidate the regulatory influence of RraA on multiple pathways associated with metabolism and pathogenesis in .
PubMed: 38934599
DOI: 10.1128/msphere.00020-24 -
Immunity, Inflammation and Disease Jun 2024To investigate the prognostic factors of patients with anti-melanoma differentiation-associated gene 5 (MDA5) positive clinically amyopathic dermatomyositis (CADM) and...
OBJECTIVE
To investigate the prognostic factors of patients with anti-melanoma differentiation-associated gene 5 (MDA5) positive clinically amyopathic dermatomyositis (CADM) and interstitial lung disease (ILD).
METHODS
A retrospective analysis was conducted on clinical data of 125 patients with anti-MDA5 + CADM-ILD collected from 10 branches in eastern China between December 2014 and December 2022. Prognostic factors were analyzed using χ test, Log-rank test, COX and logistic regression analysis.
RESULTS
In this cohort, 125 anti-MDA5 + CADM-ILD patients exhibited a rapidly progressive interstitial lung disease (RPILD) incidence of 37.6%, and an overall mortality rate of 24.8%. One patient was lost to follow-up. After diagnosis of RPILD, a mortality rate of 53.2% occurred in patients died within 3 months, and that of 5.6% appeared in those who survived for more than 3 months. Multiple factor analysis revealed that C-reactive protein (CRP) ≥ 10 mg/L (p = 0.01) and recombinant human tripartite motif containing 21 (Ro52) (+) (p = 0.003) were associated with a higher risk of RPILD in anti-MDA5 + CADM-ILD patients; CRP ≥ 10 mg/L (p = 0.018) and the presence of RPILD (p = 0.003) were identified as the factors influencing survival time in these patients, while arthritis was the protective factor (p = 0.016).
CONCLUSION
Patients with anti-MDA5 + CADM-ILD will have a higher mortality rate, and the initial 3 months after diagnosis of RPILD is considered the risk window for the dismal prognosis. Patients with CRP ≥ 10 mg/L, Ro52 (+) and RPILD may be related to a shorter survival time, while patients complicated with arthritis may present with relatively mild conditions.
Topics: Humans; Lung Diseases, Interstitial; Dermatomyositis; Interferon-Induced Helicase, IFIH1; Male; Female; Prognosis; Middle Aged; Retrospective Studies; Adult; Autoantibodies; China; Aged
PubMed: 38934403
DOI: 10.1002/iid3.1332 -
Neural Regeneration Research Jun 2024Microglial activation that occurs rapidly after closed head injury may play important and complex roles in neuroinflammation-associated neuronal damage and repair. We...
Microglial activation that occurs rapidly after closed head injury may play important and complex roles in neuroinflammation-associated neuronal damage and repair. We previously reported that induced neural stem cells can modulate the behavior of activated microglia via CXCL12/CXCR4 signaling, influencing their activation such that they can promote neurological recovery. However, the mechanism of CXCR4 upregulation in induced neural stem cells remains unclear. In this study, we found that nuclear factor-κB activation induced by closed head injury mouse serum in microglia promoted CXCL12 and tumor necrosis factor-α expression but suppressed insulin-like growth factor-1 expression. However, recombinant complement receptor 2-conjugated Crry (CR2-Crry) reduced the effects of closed head injury mouse serum-induced nuclear factor-κB activation in microglia and the levels of activated microglia, CXCL12, and tumor necrosis factor-α. Additionally, we observed that, in response to stimulation (including stimulation by CXCL12 secreted by activated microglia), CXCR4 and Crry levels can be upregulated in induced neural stem cells via the interplay among CXCL12/CXCR4, Crry, and Akt signaling to modulate microglial activation. In agreement with these in vitro experimental results, we found that Akt activation enhanced the immunoregulatory effects of induced neural stem cell grafts on microglial activation, leading to the promotion of neurological recovery via insulin-like growth factor-1 secretion and the neuroprotective effects of induced neural stem cell grafts through CXCR4 and Crry upregulation in the injured cortices of closed head injury mice. Notably, these beneficial effects of Akt activation in induced neural stem cells were positively correlated with the therapeutic effects of induced neural stem cells on neuronal injury, cerebral edema, and neurological disorders post-closed head injury. In conclusion, our findings reveal that Akt activation may enhance the immunoregulatory effects of induced neural stem cells on microglial activation via upregulation of CXCR4 and Crry, thereby promoting induced neural stem cell-mediated improvement of neuronal injury, cerebral edema, and neurological disorders following closed head injury.
PubMed: 38934402
DOI: 10.4103/NRR.NRR-D-23-01495 -
Emerging Microbes & Infections Jun 2024, a group of multi-drug resistant, Gram-positive, aerobic and partially acid-fast bacteria, are emerging causes of bacterial conjunctivitis and keratitis. However, the...
, a group of multi-drug resistant, Gram-positive, aerobic and partially acid-fast bacteria, are emerging causes of bacterial conjunctivitis and keratitis. However, the pathogenesis of keratitis is largely unknown. To address this, we used New Zealand White rabbits to develop the first eye infection model and conducted tests to study the pathogenesis mechanisms of . There is increasing evidence that biofilms play a significant role in ocular infections, leading us to hypothesize that biofilm formation is crucial for effective infection. In order to look for potential candidate genes which are important in biofilm formation and keratitis. We performed genome sequencing of two ocular isolates, -PW1004 and -PW899, to identify potential virulence factors. Through and studies, we characterized their biological roles in mediating keratitis. Our findings confirmed that is an ocular pathogen by fulfilling the Koch's postulates, and using genome sequence data, we identified encoding a mycolyltransferase, as a crucial gene in biofilm formation and causing keratitis in the rabbit model. This is the first report demonstrating the novel role of mycolyltransferase in causing ocular infections. Overall, our findings contribute to a better understanding of pathogenesis and provide a potential target for treatment. Specific inhibitors targeting TmytC could serve as an effective treatment option for infections.
PubMed: 38934251
DOI: 10.1080/22221751.2024.2373317 -
Intervirology Jun 2024This study aimed to investigate the differences between pregnant women with chronic hepatitis B virus (HBV) infection and intrafamilial infection and those without...
INTRODUCTION
This study aimed to investigate the differences between pregnant women with chronic hepatitis B virus (HBV) infection and intrafamilial infection and those without intrafamilial infection.
METHODS
HBV DNA was extracted from the sera of 16 pregnant women with chronic hepatitis B (CHB) and their family members for gene sequencing and phylogenetic analyses. A total of 74 pregnant women with CHB were followed up from the second trimester to three months postpartum. Viral markers and other laboratory indicators were compared between pregnant women with CHB with and without intrafamilial infection.
RESULTS
The phylogenetic tree showed that HBV lines in the mother-spread pedigree shared a node, whereas there was an unrelated genetic background for HBV lines in individuals without intrafamilial infection. From delivery to three months postpartum, compared with those without intrafamilial infection, pregnant women with intrafamilial infection were related negatively to HBV DNA (β=-0.43, 95% Confidence Interval [CI]: -0.76 to -0.12, p=0.009), HBeAg (β=-195.15, 95% CI: -366.35 to -23.96, p=0.027), and hemoglobin changes (β=-8.09, 95%CI: -15.54 to -0.64, p=0.035) and positively to changes in the levels of alanine aminotransferase (β=73.9, 95%CI:38.92-108.95, p<0.001) and albumin (β=2.73, 95% CI:0.23-5.23, p=0.033).
CONCLUSION
The mother-spread pedigree spread model differs from that of non-intrafamilial infections. Pregnant women with intra-familial HBV infection have less hepatitis flares and liver damage, but their HBV DNA and HBeAg levels rebound faster after delivery, than those without intra-familial infection by the virus.
PubMed: 38934174
DOI: 10.1159/000539994 -
Haematologica Jun 2024To evaluate the efficacy and safety of flumatinib in the later-line treatment of Chinese patients with Philadelphia chromosome-positive chronic-phase chronic myeloid...
To evaluate the efficacy and safety of flumatinib in the later-line treatment of Chinese patients with Philadelphia chromosome-positive chronic-phase chronic myeloid leukemia (CP-CML previously treated with tyrosine kinase inhibitors (TKIs). Patients with CML-CP were evaluated for the probabilities of responses including complete hematologic response (CHR), cytogenetic response, and molecular response (MR) and adverse events (AEs) after the later-line flumatinib therapy. Of 336 enrolled patients with median age 50 years, median duration of treatment with flumatinib was 11.04 (2-25.23) months. Patients who achieved clinical responses at baseline showed maintenance of CHR, complete cytogenetic response (CCyR)/2-log molecular response (MR2), major molecular response (MMR), and 4-log molecular response or deep molecular response (MR4/DMR) in 100%, 98.9%, 98.6%, and 92.9% patients, respectively. CHR, CCyR/MR2, MMR, and MR4/DMR responses were achieved in 86.4%, 52.7%, 49.6%, and 23.5% patients respectively, which showed the lack of respective clinical responses at baseline. The patients without response at baseline, treated with flumatinib as 2L TKI, having no resistance to prior TKI or only resistance to imatinib, with response to last TKI, and with BCR::ABL ≤10% had higher CCyR/MR2, MMR, or MR4/DMR. The AEs observed during the later-line flumatinib treatment were tolerable and consistent with those reported with the first-line therapy. Flumatinib was effective and safe in patients who are resistant or intolerant to other TKIs. In particular, 2L flumatinib treatment induced high response rates and was more beneficial to patients without previous 2G TKI resistance, thus serving as a probable treatment option for these patients.
PubMed: 38934064
DOI: 10.3324/haematol.2023.284892 -
Kidney Research and Clinical Practice Jun 2024Patients with sensitization and blood type O experience increased waiting times for deceased-donor kidney transplantation (DDKT). While allocation benefits are needed to...
BACKGROUND
Patients with sensitization and blood type O experience increased waiting times for deceased-donor kidney transplantation (DDKT). While allocation benefits are needed to resolve inequity in DDKT opportunity, whether DDKT has comparable outcomes in this disadvantaged population requires further study. This study assessed these outcomes and developed a new allocation system that balances equity and utility.
METHODS
Patients from national and hospital cohorts from two centers in Korea were categorized as B1 to B4 (according to panel reactive antibody [PRA] positivity and ABO blood type) and A1 to A4 (based on the maximal PRA% and blood type), respectively. Competing risk and Cox regression analyses were performed to assess the effects of PRA and blood type on graft failure and mortality, respectively. Based on DDKT opportunities and posttransplant outcomes, a new scoring system for kidney allocation was developed.
RESULTS
The national and hospital cohorts included 3,311 and 819 patients, respectively, who underwent DDKT. Despite the disparities in DDKT opportunities, the graft failure rates and mortality did not differ among the different PRA and blood type groups. Furthermore, posttransplantation outcomes did not differ according to the categories with different DDKT opportunities. A new scoring system to provide additional points to disadvantaged populations was developed based on the hazard ratios for DDKT.
CONCLUSION
A new allocation approach based on PRA and ABO blood types offers benefits to disadvantaged patients with fewer DDKT opportunities and could enhance equity without sacrificing utility in Korea, which has a long waiting time for DDKT.
PubMed: 38934045
DOI: 10.23876/j.krcp.24.033 -
Kidney Research and Clinical Practice Jun 2024Time-restricted feeding (TRF), devoid of calorie restriction, is acknowledged for promoting metabolic health and mitigating various chronic metabolic diseases. While TRF...
BACKGROUND
Time-restricted feeding (TRF), devoid of calorie restriction, is acknowledged for promoting metabolic health and mitigating various chronic metabolic diseases. While TRF exhibits widespread benefits across multiple tissues, there is limited exploration into its impact on kidney function. In this study, our aim was to investigate the potential ameliorative effects of TRF on kidney damage in a mouse model of cisplatin-induced acute kidney injury (AKI).
METHODS
Cisplatin-induced AKI was induced through intraperitoneal injection of cisplatin into C57BL/6 male mice. Mice undergoing TRF were provided unrestricted access to standard chow daily but were confined to an 8-hour feeding window during the dark cycle for 2 weeks before cisplatin injection. The mice were categorized into four groups: control, TRF, cisplatin, and TRF + cisplatin.
RESULTS
The tubular damage score and serum creatinine levels were significantly lower in the TRF + cisplatin group compared to the cisplatin group. The TRF + cisplatin group exhibited reduced expression of phosphorylated nuclear factor kappa B, inflammatory cytokines, and F4/80-positive macrophages compared to the cisplatin group. Furthermore, oxidative stress markers for DNA, protein, and lipid were markedly decreased in the TRF + cisplatin group compared to the cisplatin group. TUNEL-positive tubular cells, cleaved caspase-3 expression, and the Bax/Bcl-2 ratio in the TRF + cisplatin group were lower than those in the cisplatin group.
CONCLUSION
TRF, without calorie restriction, effectively mitigated kidney damage by suppressing inflammatory reactions, oxidative stress, and tubular apoptosis in a mouse model of cisplatin-induced AKI. TRF holds promise as a novel dietary intervention for preventing cisplatin-induced AKI.
PubMed: 38934035
DOI: 10.23876/j.krcp.23.351 -
Frontiers in Aging Neuroscience 2024Amid the backdrop of global aging, the increasing prevalence of cognitive decline among the elderly, particularly within the female demographic, represents a...
BACKGROUND
Amid the backdrop of global aging, the increasing prevalence of cognitive decline among the elderly, particularly within the female demographic, represents a considerable public health concern. Physical activity (PA) is recognized as an effective non-pharmacological intervention for mitigating cognitive decline in older adults. However, the relationship between different PA patterns and cognitive function (CF) in elderly women remains unclear.
METHODS
This study utilized data from National Health and Nutrition Examination Survey (NHANES) 2011-2014 to investigate the relationships between PA, PA patterns [inactive, Weekend Warrior (WW), and Regular Exercise (RE)], and PA intensity with CF in elderly women. Multivariate regression analysis served as the primary analytical method.
RESULTS
There was a significant positive correlation between PA and CF among elderly women (β-PA: 0.003, 95% CI: 0.000-0.006, = 0.03143). Additionally, WW and RE activity patterns were associated with markedly better cognitive performance compared to the inactive group (β-WW: 0.451, 95% CI: 0.216-0.685, = 0.00017; β-RE: 0.153, 95% CI: 0.085-0.221, = 0.00001). Furthermore, our results indicate a progressive increase in CF with increasing PA intensity (β-MPA- dominated: 0.16, 95% CI: 0.02-0.09, = 0.0208; β-VPA-dominated: 0.21, 95% CI: 0.09-0.34, = 0.0011; β-Total VPA: 0.31, 95% CI: -0.01-0.63, = 0.0566).
CONCLUSION
Our study confirms a positive association between PA and CF in elderly women, with even intermittent but intensive PA models like WW being correlated with improved CF. These findings underscore the significant role that varying intensities and patterns of PA play in promoting cognitive health among older age groups, highlighting the need for adaptable PA strategies in public health initiatives targeting this population.
PubMed: 38934018
DOI: 10.3389/fnagi.2024.1407423 -
Heliyon Jun 2024The remediation of dye pollutants remains a concern in contemporary water management practices. Hence, the need for efficient and cost-effective techniques for dye...
The remediation of dye pollutants remains a concern in contemporary water management practices. Hence, the need for efficient and cost-effective techniques for dye removal from wastewater. In this study, the epicarp of fruits was treated with orthophosphoric acid for enhanced porosity and efficiency in the uptake of Indigo carmine dye (ICD). Treated fruit waste (RHPW) presented morphologically distributed pores as well as high porosity with Branneur-Emmet-Teller (BET) surface area of 945.43 m/g. RHPW displayed functional groups suitable for adsorption. The maximum ICD uptake was observed at pH 5 while the maximum uptake (q) was 20.41 mg/g in the concentration range of 2-10 mg/L. Freundlich isotherm and Pseudo-second order kinetics well-described equilibrium and kinetics data respectively. This indicated a multilayered adsorption. The Dubinin-Radushkecich model energy value was 40.82 kJ/mol, indicating chemical adsorption. The ridge regression, the Lasso and the Elastic net statistical models were used to establish a positive relationship between the various adsorption operational parameters studied. Lasso provided the best result based on the estimated mean squared error. The RHPW-ICD adsorption system was more favorable at room temperature, as the removal efficiency decreased with temperature rise. The findings established fruit epicarp as an economical and sustainable precursor for the preparation of potent adsorbent for Indigo carmine dye removal. This can find possible application in wastewater treatment.
PubMed: 38933985
DOI: 10.1016/j.heliyon.2024.e32121