Nevin Manimala

Gut Microbes. 2024 Jan-Dec;16(1):2315631. doi: 10.1080/19490976.2024.2315631. Epub 2024 Feb 22.

ABSTRACT

Immune checkpoint inhibitors (ICI) have been positioned as a standard of care for patients with advanced non-small-cell lung carcinomas (NSCLC). A pilot clinical trial has reflected optimistic association between supplementation with Clostridium butyricum MIYAIRI 588 (CBM588) and ICI efficacy in NSCLC. However, it remains to be established whether this biotherapeutic strain may be sufficient to heighten the immunogenicity of the tumor draining lymph nodes to overcome resistance to ICI. Herein, we report that supplementation with CBM588 led to an improved responsiveness to antibody targeting programmed cell death protein 1 (aPD-1). This was statistically associated with a significant decrease in α-diversity of gut microbiota from CBM588-treated mice upon PD-1 blockade. At the level of the tumor-draining lymph node, such combination of treatment significantly lowered the frequency of microbiota-modulated subset of regulatory T cells that express Retinoic Orphan Receptor gamma t (Ror$\gamma$t⁺ Treg). Specifically, this strongly immunosuppressive was negatively correlated with the abundance of bacteria that belong to the family of Ruminococcaceae. Accordingly, the colonic expression of both indoleamine 2,3-Dioxygenase 1 (IDO-1) and interleukin-10 (IL-10) were heightened in mice with greater PD-1 blockade efficacy. The CBM588-induced ability to secrete Interleukin-10 of lamina propria mononuclear cells was heightened in tumor bearers when compared with cancer-free mice. Conversely, blockade of interleukin-10 signaling preferentially enhanced the capacity of CD8⁺ T cells to secrete Interferon gamma when being cocultured with CBM588-primed lamina propria mononuclear cells of tumor-bearing mice. Our results demonstrate that CBM588-centered intervention can adequately improve intestinal homeostasis and efficiently overcome resistance to PD-1 blockade in mice.

PMID:38385162 | DOI:10.1080/19490976.2024.2315631

Synth Syst Biotechnol. 2024 Feb 8;9(2):196-208. doi: 10.1016/j.synbio.2024.01.012. eCollection 2024 Jun.

ABSTRACT

The goal of this study was to use statistical optimization to change the nutritional and environmental conditions so that Streptomyces baarensis MH-133 could make more active metabolites. Twelve trials were used to screen for critical variables influencing productivity using the Placket-Burman Design method. S. baarensis MH-133 is significantly influenced by elicitation, yeast extract, inoculum size, and incubation period in terms of antibacterial activity. A total of 27 experimental trials with various combinations of these factors were used to carry out the response surface technique using the Box-Behnken design. The analyses revealed that the model was highly significant (p < 0.001), with a lack-of-fit of 0.212 and a coefficient determination (R2) of 0.9224. Additionally, the model predicted that the response as inhibition zone diameter would reach a value of 27 mm. Under optimal conditions, S. baarensis MH-133 produced 18.0 g of crude extract to each 35L and was purified with column chromatography. The active fraction exhibiting antibacterial activity was characterized using spectroscopic analysis. The MIC and MBC values varied between 37.5 and 300 μg/ml and 75 and 300 μg/ml, respectively. In conclusion, the biostatistical optimization of the active fraction critical variables, including environmental and nutritional conditions, enhances the production of bioactive molecules by Streptomyces species.

PMID:38385149 | PMC:PMC10876617 | DOI:10.1016/j.synbio.2024.01.012

Front Cardiovasc Med. 2024 Feb 7;11:1279890. doi: 10.3389/fcvm.2024.1279890. eCollection 2024.

ABSTRACT

BACKGROUND: An increase in deaths has been perceived during the pandemic, which cannot be explained only by COVID-19. The actual number of deaths far exceeds the recorded data on deaths directly related to SARS-CoV-2 infection. Data from early and short-lived pandemic studies show a dramatic shift in cardiovascular mortality. Grounded in the post-pandemic era, macroscopic big data on cardiovascular mortality during the pandemic need to be further reviewed and studied, which is crucial for cardiovascular disease prevention and control.

METHODS: We retrieved and collected data associated with cardiovascular disease mortality from the National Vital Statistic System from the Center for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) platform based on the ICD-10 codes. We applied regression analysis to characterize overall cardiovascular disease mortality trends from 2010 to 2023 and built a time series model to predict mortality for 2020-2023 based on mortality data from 2010 to 2019 in order to affirm the existence of the excess deaths by evaluating observed vs. predicted mortality. We also conducted subgroup analyses by sex, age and race/ethnicity for the purpose of obtaining more specific sociodemographic information.

RESULTS: All-cause age-standardised mortality rates (ASMRs) for CVD dramatically increased between 2019 and 2021[annual percentage change (APC) 11.27%, p < 0.01], and then decreased in the following 2021-2023(APC: -7.0%, p < 0.01). Subgroup analyses found that the ASMR change was most pronounced in Alaska Indians/Native American people (APC: 16.5% in 2019-2021, -12.5% in 2021-2023, both p < 0.01), Hispanics (APC: 12.1% in 2019-2021, -12.2% in 2021-2023, both p < 0.05) and non-Hispanic Black people (APC:11.8% in 2019-2021, -10.3% in 2021-2023, both p < 0.01)whether during the increasing or declining phase. Similarly, the ASMR change was particularly dramatic for the 25-44 age group (APC:19.8% in 2019-2021, -15.4% in 2021-2023, both p < 0.01) and males (APC: 11.5% in 2019-2021, -7.6% in 2021-2023, both p < 0.01). By the end of 2023, the proportion of COVID-related excess death remained high among the elderly (22.4%), males (42.8%) and Alaska Indians/Native American people(39.7%). In addition, we did not find the presence of excess deaths in the young (25-44) and middle-aged cohort (45-64) in 2023, while excess deaths remained persistent in the elderly.

CONCLUSIONS: All-cause ASMRs for CVD increased notably during the initial two years of the COVID-19 pandemic and then witnessed a decline in 2021-2023. The cohorts (the young, males and minorities) with the steepest rise in mortality decreased at the fastest rate instead. Previous initiatives to promote cardiovascular health were effective, but further research on cardiovascular healthcare for the elderly and racial disparities should be attached to priority considering the presence of sociodemographic differences in CVD death.

PMID:38385134 | PMC:PMC10879411 | DOI:10.3389/fcvm.2024.1279890

Front Cardiovasc Med. 2024 Feb 7;11:1286100. doi: 10.3389/fcvm.2024.1286100. eCollection 2024.

ABSTRACT

BACKGROUND: The association between low socioeconomic status (SES) and worse surgical outcomes has become an emerging area of interest. Literature has demonstrated that carotid artery stenting (CAS) poses greater risk of postoperative complications, particularly stroke, than carotid endarterectomy (CEA). This study aims to compare the impact of low SES on patients undergoing CAS vs. CEA.

METHODS: The National Inpatient Sample (NIS) was queried for patients undergoing CAS and CEA from 2010 to 2015. Patients were stratified by highest and lowest median income quartiles by zip code and compared through demographics, hospital characteristics, and comorbidities defined by the Charlson Comorbidity Index (CCI). Primary outcome was in-hospital mortality. Secondary outcomes included acute kidney injury (AKI), post-operative stroke, sepsis, and bleeding requiring reoperation.Multivariable logistic regression was used to determine the effect of SES on outcomes.

RESULTS: Five thousand four hundred twenty-five patients underwent CAS (Low SES: 3,516 (64.8%); High SES: 1,909 (35.2%) and 38,399 patients underwent CEA (Low SES: 22,852 (59.5%); High SES: 15,547 (40.5%). Low SES was a significant independent predictor of mortality [OR = 2.07 (1.25-3.53); p = 0.005] for CEA patients, but not for CAS patients [OR = 1.21 (CI 0.51-2.30); p = 0.68]. Stroke was strongly associated with low SES, CEA patients (Low SES = 1.5% vs. High SES = 1.2%; p = 0.03), while bleeding was with high SES, CAS patients (Low SES = 5.3% vs. High SES = 7.1%; p = 0.01). CCI was a strong predictor of mortality for both procedures [CAS: OR1.45 (1.17-1.80); p < 0.001. CEA: OR1.60 (1.45-1.77); p < 0.001]. Advanced age was a predictor of mortality post-CEA [OR = 1.03 (1.01-1.06); p = 0.01]. While not statistically significant, advanced age and increased mortality trended towards a positive association in CAS [OR = 1.05 (1.00-1.10); p = 0.05].

CONCLUSIONS: Low SES is a significant independent predictor of post-operative mortality in patients who underwent CEA, but not CAS. CEA is also associated with higher incidence of stroke in low SES patients. Findings demonstrate the impact of SES on outcomes for patients undergoing carotid revascularization procedures. Prospective studies are warranted to further evaluate this disparity.

PMID:38385132 | PMC:PMC10879273 | DOI:10.3389/fcvm.2024.1286100

Oncol Lett. 2024 Feb 6;27(4):142. doi: 10.3892/ol.2024.14275. eCollection 2024 Apr.

ABSTRACT

Locoregional recurrences and distant metastases are major problems for patients with squamous cell carcinoma of the head and neck (SCCHN). Because SCCHN is a heterogeneous group of tumours with varying characteristics, the present study concentrated on the subgroup of squamous cell carcinoma of the oral tongue (SCCOT) to investigate the use of machine learning approaches to predict the risk of recurrence from routine clinical data available at diagnosis. The approach also identified the most important parameters that identify and classify recurrence risk. A total of 66 patients with SCCOT were included. Clinical data available at diagnosis were analysed using statistical analysis and machine learning approaches. Tumour recurrence was associated with T stage (P=0.001), radiological neck metastasis (P=0.010) and diabetes (P=0.003). A machine learning model based on the random forest algorithm and with attendant explainability was used. Whilst patients with diabetes were overrepresented in the SCCOT cohort, diabetics had lower recurrence rates (P=0.015 after adjusting for age and other clinical features) and an improved 2-year survival (P=0.025) compared with non-diabetics. Clinical, radiological and histological data available at diagnosis were used to establish a prognostic model for patients with SCCOT. Using machine learning to predict recurrence produced a classification model with 71.2% accuracy. Notably, one of the findings of the feature importance rankings of the model was that diabetics exhibited less recurrence and improved survival compared with non-diabetics, even after accounting for the independent prognostic variables of tumour size and patient age at diagnosis. These data imply that the therapeutic manipulation of glucose levels used to treat diabetes may be useful for patients with SCCOT regardless of their diabetic status. Further studies are warranted to investigate the impact of diabetes in other SCCHN subtypes.

PMID:38385115 | PMC:PMC10877229 | DOI:10.3892/ol.2024.14275

Int J Biol Sci. 2024 Feb 4;20(4):1452-1470. doi: 10.7150/ijbs.90226. eCollection 2024.

ABSTRACT

A growing number of studies have revealed an association between proteasome activator complex subunit 2 (PSME2) and the progression of various forms of cancer. However, the effect of PSME2 on osteosarcoma progression is unknown. Pan-cancer analyses focused on the immunological activity and prognostic relevance of PSME2 have yet to be conducted. The Cancer Genome Atlas and Genome-Tissue Expression databases were leveraged to evaluate PSME2 expression and activity across 33 cancer types. Significant PSME2 dysregulation was noted in a wide range of cancer types and this gene was found to offer significant diagnostic and prognostic utility in most analyzed cancers. From a mechanistic perspective, PSME2 expression levels were correlated with DNA methylation, DNA repair, genomic instability, and TME scores in multiple cancer types. PSME2 was subsequently established as a pan-cancer biomarker of M1 macrophage infiltration based on a combination of bulk, single-cell, and spatial transcriptomic data and confirmatory fluorescent staining results. In osteosarcoma cells, overexpressing PSME2 significantly suppressed tumor proliferative, migratory, and invasive activity. Screening efforts also successfully identified the PSME2-activating drug irinotecan, which can synergistically promote the death of osteosarcoma cells when combined with the chemotherapeutic drug paclitaxel. As a biomarker of M1 macrophage infiltration, PSME2 expression levels may offer insight into tumor development and progression for a wide range of cancers including osteosarcoma, emphasizing its potential utility as a prognostic and therapeutic target worthy of further study.

PMID:38385075 | PMC:PMC10878157 | DOI:10.7150/ijbs.90226

Scars Burn Heal. 2024 Feb 20;10:20595131241230739. doi: 10.1177/20595131241230739. eCollection 2024 Jan-Dec.

ABSTRACT

INTRODUCTION: Postburn scarring often presents a specific reconstructive challenge from both functional and cosmetic perspectives. The purpose of this study was to investigate whether autologous nanofat harvested from the donor site of full skin or a skin flap can be reused for the treatment of early postburn scaring.

METHODS: From July 2018 to April 2022, patients with early postburn scarring underwent scar reconstruction surgery with full-thickness skin or a skin flap for a contour deformity and/or scar contracture, and autologous nanofat grafting was performed during the same operation. The Vancouver Scar Score (VSS) and the itch and pain scores were evaluated at the preoperation time point as well as at 2-3 weeks and 3-months postoperation. A comparison was made among the same patients at different time points.

RESULTS: A total of 17 patients, aged from 18 months to 62 years old were included in this analysis. The VSS was reduced from 10.00 ± 2.12 to 7.41 ± 1.277 at the 2-3-week postoperation time point, and to 5.53 ± 1.37 at the 3-month postoperation time point. The pain and itch score were reduced from 4.65 ± 1.37 and 6.35 ± 1.27, to 3.70 ± 1.10 and 4.94 ± 1.30 at the 2-3-week postoperation time point, and to 3.00 ± 1.28 and 3.94 ± 0.97 at the 3-month postoperation time point respectively. The VSS and pain and itch scores showed a statistically significant reduction (P < 0.05) at the 2-3-week and 3-month postoperative follow-ups compared with the preoperation time point.

CONCLUSION: Autologous nanofat grafting from donor sites of full thickness skin or skin flap may be a promising treatment for an early postburn scaring as it promotes scar softening, improves itching and pain within the scar. However, this is a small case series with only 17 patients. Further conclusions need to be drawn through expanded samples for randomized controlled clinical trials.

LAY SUMMARY: Hypertrophic scarring is the most common complication after partial thickness burn injury, and the complex pathogenesis and prolonged dynamic process render treatments only marginally effective. In the past few decades, with the technological advances of liposuction and fat grafting, nanofat grafting has been used in a variety of surgical fields, including wound healing, scleroderma, facial rejuvenation, and neuralgia. However, the role of nanofat grafting is not well documented in the prevention and treatment of early postburn scarring. Full-thickness skin grafting or skin flap transplantation is the most common method for the reconstruction of a hypertrophic scaring until now. In the current study, we harvested subcutaneous fat during the preparation of the full-thickness skin or skin flap, prepared nanofat and injected it in the scar located at a nonsurgical site. Comparison of the pre- and postoperation scores for scar color, scar thickness, scar stiffness, and scar regularity showed that the postoperation scores were decreased significantly and that there was a significant improvement in scar pigmentation and thickness as well astheaesthetic outcome after treatment. Most importantly, reductions in the scores for pain and itching could be assessed objectively. It seems that the nanofat grafting is a potential method for prevention and treatment for early postburn scaring.

PMID:38385064 | PMC:PMC10880530 | DOI:10.1177/20595131241230739

Int J Endocrinol. 2024 Feb 14;2024:8229604. doi: 10.1155/2024/8229604. eCollection 2024.

ABSTRACT

OBJECTIVE: This study aims to explore the relationships between serum indoxyl sulfate (IS) and Klotho protein levels with vascular calcification in patients with chronic kidney disease (CKD) stages 3-5.

METHODS: From December 2021 to January 2023, a total of 108 CKD patients in stages 3-5 were enrolled in this cross-sectional investigation. Demographic information and routine clinical biochemistry test results were gathered. Serum levels of IS and Klotho were quantified through enzyme-linked immunosorbent assays. Furthermore, multislice spiral computed tomography was employed to evaluate vascular calcification. The association between serum IS or Klotho levels and abdominal aorta calcification was assessed using univariate analysis and logistic regression analyses.

RESULTS: With the progression of CKD stages, serum creatinine, phosphorus, intact parathyroid hormone (iPTH), serum IS, and abdominal aortic calcification exhibited incremental trends, while serum calcium and Klotho protein levels showed a diminishing trend, with statistically significant differences (P < 0.05). Significant differences were observed in age, blood phosphorus, calcium, total parathyroid hormone, serum IS, and Klotho protein levels between patients with and without aortic calcification (P < 0.05). Logistic regression analysis demonstrated that advanced age, high IS level, and low Klotho protein level were independent risk factors for abdominal aortic calcification in CKD patients (P < 0.05).

CONCLUSION: This study indicates elevated serum IS levels and decreased Klotho protein levels in CKD patients. High IS level and low Klotho level were independent risk factors for abdominal aortic calcification.

PMID:38385060 | PMC:PMC10881242 | DOI:10.1155/2024/8229604

Front Pharmacol. 2024 Feb 6;14:1338975. doi: 10.3389/fphar.2023.1338975. eCollection 2023.

ABSTRACT

Objective: This study aims to evaluate the clinical and preclinical efficacy of SMI in treating CHF, and to summarize the relevant mechanisms of action in order to provide evidence for its role in CHF treatment. Methods: A systematic computerized search of eight databases and three registry systems was performed, with the time frame spanning from the inception of the databases to 30 June 2023. Strict procedures were used for data extraction, quality assessment, and data analysis. The methodological quality of the included studies was assessed using RoB-2 and SYRCLE tools. Statistical analysis was performed using Rev Man 5.4 software, using either fixed-effects or random-effects models. Results: A total of 25 clinical trials (including test group 1,367 patients, control group 1,338 patients) and 11 animal studies (including 201 animals) were included in this review. The meta-analysis of clinical studies showed that SMI can improve cardiac function indicators (LVEF, LVFS, LVEDV, LVESV, LVEDD, LVESD) (p < 0.00001), reduce BNP/NT-proBNP levels (p < 0.01), and improve inflammatory markers (hs-CRP, TNF-α, IL-6) (p < 0.00001) and endothelin (ET) levels (p < 0.0001). In animal studies, SMI demonstrated improved cardiac function (LVEF, LVFS) (p < 0.05), and improved heart failure markers (NT-proBNP, p < 0.05) when compared to control groups. Conclusion: This study represents the first meta-analysis which includes both preclinical and clinical studies on SMI. Clinical and animal studies have shown that SMI can improve cardiac function in CHF patients through its anti-apoptotic effects, antioxidant activities, anti-inflammatory effects, and improvement of myocardial metabolism. This study has certain limitations in terms of literature quality, quantity, and follow-up time. Therefore, the conclusions drawn from this study may require further validation through larger-scale, high-quality RCT trials.

PMID:38385058 | PMC:PMC10880451 | DOI:10.3389/fphar.2023.1338975

Front Neurol. 2024 Feb 7;15:1367735. doi: 10.3389/fneur.2024.1367735. eCollection 2024.

ABSTRACT

INTRODUCTION: To date, no systematic review or meta-analysis has critically evaluated the relevance of using optokinetic after-nystagmus (OKAN) in diagnosis of vestibular disorders. To assess the role of OKAN in diagnosis of vestibular disorders, the OKAN time constant (TC) between patients with vestibular disorders and healthy participants will be compared.

METHODS: Automated search strategies were carried out in the Embase, Medline PubMed, Web of Science, and Scopus databases from inception to December 2023. The following inclusion criteria were applied: (1) evaluation of OKAN in individuals with vestibular disorders, (2) clinical trials, and (3) inclusion of healthy individuals as the control group. Exclusion criteria were: (1) animal studies, (2) non-clinical trial study designs, (3) assessment of non-vestibular disorders, (4) no examination of OKAN TC, (5) only examination of healthy participants, (6) studies published in a language other than English, (7) no healthy participants as control group, (8) case reports, and (9) only abstract available. The random-effects model was used to pool the data. The Joanna Briggs Institute (JBI) Critical Appraisal Tools was used to assess the risk of bias. The quality assessment was performed with the aid of the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies, provided by NHLBI. The PRISMA guidelines were used as reporting guidelines. The main outcome of this study was the between-group mean difference (MDbetween) in OKAN TC and its 95% confidence interval between patients with vestibular disorders and healthy participants.

RESULTS: Seven out of 244 screened articles were included that studied 289 participants. The overall mean difference (MD = -7.08) with a 95% CI of [-10.18; -3.97] was significant (p = 0.014). The heterogeneity was significant (p = 0.02). Quality assessment was generally good (76%). The risk of bias was low in five studies and moderate in two studies.

CONCLUSION: The results demonstrate that OKAN TC is significantly shorter in patients with vestibular disorders compared to healthy controls. This finding is important for future research, particularly with the emergence of novel clinical tools and diagnostic syndromes.

SYSTEMATIC REVIEW: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=442695.

PMID:38385042 | PMC:PMC10879310 | DOI:10.3389/fneur.2024.1367735