In vitro evaluation of antioxidant potential of polysaccharides and oligosaccharides extracted from three different seaweeds.

Bioactive polysaccharides and oligosaccharides were successfully extracted from three distinct seaweeds: Sargassum sp., Graciallaria sp., and Ulva sp. utilizing various extraction techniques. The obtained polysaccharides and oligosaccharides were subjected to comprehensive characterization, and their potential antioxidant properties were assessed using a Hep G2 cell model. Analysis via FTIR spectroscopy unveiled the presence of sulfate groups in the polysaccharides and oligosaccharides derived from Sargassum sp. The antioxidant capabilities were assessed through various assays (DPPH, ABTS, Fe-ion chelation, and reducing power), revealing that SAR-OSC exhibited superior antioxidant activity than others. This was attributed to its higher phenolic content (24.6 µg/mg), FRAP value (36 µM Vitamin C/g of extract), and relatively low molecular weight (5.17 kDa). The study also investigated the protective effects of these polysaccharides and oligosaccharides against oxidative stress-induced damage in Hep G2 cells by measuring ROS production and intracellular antioxidant enzyme expressions (SOD, GPx, and CAT). Remarkably, SAR-OSC demonstrated the highest efficacy in protecting Hep G2 cells reducing ROS production and downregulating SOD, GPx, and CAT expressions. Current findings have confirmed that the oligosaccharides extracted by the chemical method show higher antioxidant activity, particularly SAR-OSC, and robust protective abilities in the Hep G2 cells.

Benmelstobart, anlotinib and chemotherapy in extensive-stage small-cell lung cancer: a randomized phase 3 trial.

Immunochemotherapy is the first-line standard for extensive-stage small-cell lung cancer (ES-SCLC). Combining the regimen with anti-angiogenesis may improve efficacy. ETER701 was a multicenter, double-blind, randomized, placebo-controlled phase 3 trial that investigated the efficacy and safety of benmelstobart (a novel programmed death-ligand 1 (PD-L1) inhibitor) with anlotinib (a multi-target anti-angiogenic small molecule) and standard chemotherapy in treatment-naive ES-SCLC. The ETER701 trial assessed two primary endpoints: Independent Review Committee-assessed progression-free survival per RECIST 1.1 and overall survival (OS). Here the prespecified final progression-free survival and interim OS analysis is reported. Patients randomly received benmelstobart and anlotinib plus etoposide/carboplatin (EC; n = 246), placebo and anlotinib plus EC (n = 245) or double placebo plus EC ('EC alone'; n = 247), followed by matching maintenance therapy. Compared with EC alone, median OS was prolonged with benmelstobart and anlotinib plus EC (19.3 versus 11.9 months; hazard ratio 0.61; P = 0.0002), while improvement of OS was not statistically significant with anlotinib plus EC (13.3 versus 11.9 months; hazard ratio 0.86; P = 0.1723). The incidence of grade 3 or higher treatment-related adverse events was 93.1%, 94.3% and 87.0% in the benmelstobart and anlotinib plus EC, anlotinib plus EC, and EC alone groups, respectively. This study of immunochemotherapy plus multi-target anti-angiogenesis as first-line treatment achieved a median OS greater than recorded in prior randomized studies in patients with ES-SCLC. The safety profile was assessed as tolerable and manageable. Our findings suggest that the addition of anti-angiogenesis therapy to immunochemotherapy may represent an efficacious and safe approach to the management of ES-SCLC. ClinicalTrials.gov identifier: NCT04234607 .

True lumen expansion but no aortic remodeling following thoracic endografting and distal bare-stent for subacute complicated Type B aortic dissection.

BACKGROUND: The effects of thoracic endovascular aneurysm repair (TEVAR) with additional distal bare metal stents (BMSs) in patients with subacute complicated type B aortic dissection (cTBAD) are unclear and are investigated in this retrospective study. METHODS: The medical records of 67 patients who received TEVAR due to subacute cTBAD were reviewed. Areas of true lumen (TL) and false lumen at 5 levels-- pulmonary artery (PA), diaphragm, renal artery (RA), middle of the infrarenal aorta, and aortic bifurcation-were measured using computed tomography before and 3, 6, and 12 months after surgery. The TL ratio (TL area/total aortic area) and total aortic area at each time point were compared between the TEVAR+BMS (n=37) and TEVAR-only (n=30) groups. The effects of BMS use and time were evaluated using generalized estimating equations and generalized linear regression models. RESULTS: Baseline characteristics, remodeling types, and clinical outcomes did not differ significantly between the 2 groups. Postoperative TL ratios at the diaphragm and RA were significantly higher in the TEVAR+BMS group than in the TEVAR-only group (p < 0.05). BMS use and time had significant interaction effects at the PA, diaphragm, and RA (all p < 0.05), but effects on total aortic area were not significant at any of the 5 parts. TL ratios at the diaphragm and RA exhibtied greater improvement in the TEVAR+BMS group than in the TEVAR-only group at postoperative months 6 and 12 (all p < 0.001). Aortic diameters at all 5 parts were significantly smaller in the TEVAR+BMS group than in the TEVAR-only group (all p < 0.05). CONCLUSION: In patients with subacute cTBAD, TEVAR with BMS implantation effectively expands the TL from the thoracic aorta to the RA but neither enhances aortic remodeling nor elicits any change in total aortic area in whole dissected aorta relative to TEVAR only.

Formation of Zwitterionic and Self-Healable Hydrogels via Amino-yne Click Chemistry for Development of Cellular Scaffold and Tumor Spheroid Phantom for MRI.

In situ-forming biocompatible hydrogels have great potential in various medical applications. Here, we introduce a pH-responsive, self-healable, and biocompatible hydrogel for cell scaffolds and the development of a tumor spheroid phantom for magnetic resonance imaging. The hydrogel (pMAD) was synthesized via amino-yne click chemistry between poly(2-methacryloyloxyethyl phosphorylcholine-co-2-aminoethylmethacrylamide) and dialkyne polyethylene glycol. Rheology analysis, compressive mechanical testing, and gravimetric analysis were employed to investigate the gelation time, mechanical properties, equilibrium swelling, and degradability of pMAD hydrogels. The reversible enamine and imine bond mechanisms leading to the sol-to-gel transition in acidic conditions (pH ≤ 5) were observed. The pMAD hydrogel demonstrated potential as a cellular scaffold, exhibiting high viability and NIH-3T3 fibroblast cell encapsulation under mild conditions (37 °C, pH 7.4). Additionally, the pMAD hydrogel also demonstrated the capability for in vitro magnetic resonance imaging of glioblastoma tumor spheroids based on the chemical exchange saturation transfer effect. Given its advantages, the pMAD hydrogel emerges as a promising material for diverse biomedical applications, including cell carriers, bioimaging, and therapeutic agent delivery.

Development of a Radiolabeled Cyclin-Dependent Kinases 4 and 6 (CDK4/6) Inhibitor for Brain and Cancer PET Imaging.

The synthesis, biochemical evaluation and radiosynthesis of a cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor and radioligand was performed. NT431, a newly synthesized 4-fluorobenzyl-abemaciclib, exhibited high potency to CDK4/6 and against four cancer cell lines with IC50 similar to that of the parent abemaciclib. We performed a two-step one-pot radiosynthesis to produce [18F]NT431 with good radiochemical yield (9.6 ± 3%, n = 3, decay uncorrected), high radiochemical purity (>95%), and high molar activity (>370 GBq/µmol (>10.0 Ci/µmol). In vitro autoradiography confirmed the specific binding of [18F]NT431 to CDK4/6 in brain tissues. Dynamic PET imaging supports that both [18F]NT431 and the parent abemaciclib crossed the BBB albeit with modest brain uptake. Therefore, we conclude that it is unlikely that NT431 or abemaciclib (FDA approved drug) can accumulate in the brain in sufficient concentrations to be potentially effective against breast cancer brain metastases or brain cancers. However, despite the modest BBB penetration, [18F]NT431 represents an important step towards the development and evaluation of a new generation of CDK4/6 inhibitors with superior BBB penetration for the treatment and visualization of CDK4/6 positive tumors in the CNS. Also, [18F]NT431 may have potential application in peripheral tumors such as breast cancer and other CDK4/6 positive tumors.

RNF149 Destabilizes IFNGR1 in Macrophages to Favor Post-Infarction Cardiac Repair.

BACKGROUND: Macrophage-driven inflammation critically involves in cardiac injury and repair following myocardial infarction (MI). However, the intrinsic mechanisms that halt the immune response of macrophages, which is critical to preserve homeostasis and effective infarct repair, remain to be fully defined. Here, we aimed to determine the ubiquitination-mediated regulatory effects on averting exaggerated inflammatory responses in cardiac macrophages. METHODS: We used transcriptome analysis of mouse cardiac macrophages and bone marrow-derived macrophages to identify the E3 ubiquitin ligase RNF149 (RING finger protein 149) as a modulator of macrophage response to MI. Employing loss-of-function methodologies, bone marrow transplantation approaches, and adenovirus-mediated RNF149 overexpression in macrophages, we elucidated the functional role of RNF149 in MI. We explored the underlying mechanisms through flow cytometry, transcriptome analysis, immunoprecipitation/mass spectrometry analysis, and functional experiments. RNF149 expression was measured in the cardiac tissues of patients with acute MI and healthy controls. RESULTS: RNF149 was highly expressed in murine and human cardiac macrophages at the early phase of MI. Knockout of RNF149, transplantation of Rnf149-/- bone marrow, and bone marrow macrophage-specific RNF149-knockdown markedly exacerbated cardiac dysfunction in murine MI models. Conversely, overexpression of RNF149 in macrophages attenuated the ischemia-induced decline in cardiac contractile function. RNF149 deletion increased infiltration of proinflammatory monocytes/macrophages, accompanied by a hastened decline in reparative subsets, leading to aggravation of myocardial apoptosis and impairment of infarct healing. Our data revealed that RNF149 in infiltrated macrophages restricted inflammation by promoting ubiquitylation-dependent proteasomal degradation of IFNGR1 (interferon gamma receptor 1). Loss of IFNGR1 rescued deleterious effects of RNF149 deficiency on MI. We further demonstrated that STAT1 activation induced Rnf149 transcription, which, in turn, destabilized the IFNGR1 protein to counteract type-II IFN (interferon) signaling, creating a feedback control mechanism to fine-tune macrophage-driven inflammation. CONCLUSIONS: These findings highlight the significance of RNF149 as a molecular brake on macrophage response to MI and uncover a macrophage-intrinsic posttranslational mechanism essential for maintaining immune homeostasis and facilitating cardiac repair following MI.

The multifaceted perspectives on the regulation of lncRNAs in hepatocellular carcinoma ferroptosis: from bench-to-bedside.

Despite being characterized by high malignancy, high morbidity, and low survival rates, the underlying mechanism of hepatocellular carcinoma (HCC) has not been fully elucidated. Ferroptosis, a non-apoptotic form of regulated cell death, possesses distinct morphological, biochemical, and genetic characteristics compared to other types of cell death. Dysregulated actions within the molecular network that regulates ferroptosis have been identified as significant contributors to the progression of HCC. Long non-coding RNAs (lncRNAs) have emerged as influential contributors to diverse cellular processes, regulating gene function and expression through multiple mechanistic pathways. An increasing body of evidence indicates that deregulated lncRNAs are implicated in regulating malignant events such as cell proliferation, growth, invasion, and metabolism by influencing ferroptosis in HCC. Therefore, elucidating the inherent role of ferroptosis and the modulatory functions of lncRNAs on ferroptosis in HCC might promote the development of novel therapeutic interventions for this disease. This review provides a succinct overview of the roles of ferroptosis and ferroptosis-related lncRNAs in HCC progression and treatment, aiming to drive the development of promising therapeutic targets and biomarkers for HCC patients.

Anti-osteoporosis drugs reduce mortality in cancer patients: A national cohort study of elderly with vertebral fractures.

Introduction: The most prevalent type of fragility fractures is osteoporotic vertebral fractures (OVFs). However, only a few studies have examined the relationship between anti-osteoporosis treatments and malignancy-related mortality following an OVF. The goal of this study is to determine the effect of anti-osteoporosis therapy on mortality in OVF patients with and without cancer. Method: Data from older people over the age of 65 who were hospitalised for OVFs between 1 January 2003 and 31 December 2018 were analysed retrospectively. A total of 6139 persons getting osteoporosis treatment and 28,950 who did not receive treatment were analysed, together with 2 sets of patients, comprising cancer patients (794) and cancer-free patients (5342), using anti-osteoporosis medication or not, in 1:1 propensity score-matched analyses. The hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated. Results: In all, 35,089 patients with OVFs were included in the population; 29,931 people (85.3%) were women, and the mean (standard deviation) age was 78.13 (9.27) years. Overall survival was considerably higher in those undergoing osteoporosis therapy. This was true both for those without cancer (adjusted HR 0.55; 95% CI 0.51-0.59; P<.0001) as well as those with cancer (adjusted HR 0.72; 95% CI 0.62-0.84; P<.0001). Even among cancer patients, those who received anti-osteoporotic drugs had a lower mortality rate than those who did not. Conclusion: Our findings suggest that anti-osteoporosis therapy should be initiated regardless of the presence of cancer in the elderly, as it increases survival following OVFs.

Circadian Rhythm Disruption in Hepatocellular Carcinoma Investigated by Integrated Analysis of Bulk and Single-Cell RNA Sequencing Data.

Circadian rhythms are essential regulators of a multitude of physiological and behavioral processes, such as the metabolism and function of the liver. Circadian rhythms are crucial to liver homeostasis, as the liver is a key metabolic organ accountable for the systemic equilibrium of the body. Circadian rhythm disruption alone is sufficient to cause liver cancer through the maintenance of hepatic metabolic disorder. Although there is evidence linking CRD to hepatocarcinogenesis, the precise cellular and molecular mechanisms that underlie the circadian crosstalk that leads to hepatocellular carcinoma remain unknown. The expression of CRD-related genes in HCC was investigated in this study via bulk RNA transcriptomic analysis and single-cell sequencing. Dysregulated CRD-related genes are predominantly found in hepatocytes and fibroblasts, according to the findings. By using a combination of single-cell RNA sequencing and bulk RNA sequencing analyses, the dysregulated CRD-related genes ADAMTS13, BIRC5, IGFBP3, MARCO, MT2A, NNMT, and PGLYRP2 were identified. The survival analysis using the Kaplan-Meier method revealed a significant correlation between the expression levels of BIRC5 and IGFBP3 and the survival of patients diagnosed with HCC.

ZBTB11 Depletion Targets Metabolic Vulnerabilities in K-Ras Inhibitor Resistant PDAC.

Over 95% of pancreatic ductal adenocarcinomas (PDAC) harbor oncogenic mutations in K-Ras. Upon treatment with K-Ras inhibitors, PDAC cancer cells undergo metabolic reprogramming towards an oxidative phosphorylation-dependent, drug-resistant state. However, direct inhibition of complex I is poorly tolerated in patients due to on-target induction of peripheral neuropathy. In this work, we develop molecular glue degraders against ZBTB11, a C2H2 zinc finger transcription factor that regulates the nuclear transcription of components of the mitoribosome and electron transport chain. Our ZBTB11 degraders leverage the differences in demand for biogenesis of mitochondrial components between human neurons and rapidly-dividing pancreatic cancer cells, to selectively target the K-Ras inhibitor resistant state in PDAC. Combination treatment of both K-Ras inhibitor-resistant cell lines and multidrug resistant patient-derived organoids resulted in superior anti-cancer activity compared to single agent treatment, while sparing hiPSC-derived neurons. Proteomic and stable isotope tracing studies revealed mitoribosome depletion and impairment of the TCA cycle as key events that mediate this response. Together, this work validates ZBTB11 as a vulnerability in K-Ras inhibitor-resistant PDAC and provides a suite of molecular glue degrader tool compounds to investigate its function.

[Expression and Clinical Significance of LINC00475 in Multiple Myeloma].

OBJECTIVE: To investigate the relative expression level and clinical significance of LINC00475 in serum of patients with multiple myeloma (MM). METHODS: The expression of LINC00475 in serum of 108 MM patients and five MM cell lines including RPMI 8226, NCI-H929, U266, OPM2 and CAG were detected by real-time fluorescence quantitative PCR. The diagnostic value of LINC00475 in MM was evaluated by receiver operating characteristic (ROC) curve analysis. The correlation of LINC00475 with patients' characteristics was analyzed. RESULTS: Compared with control groups, the expression of LINC00475 was up-regulated in serum of MM patients and MM cell lines (all P < 0.05). ROC curve analysis showed that the optimal cut-off value of LINC00475 was 262.4, the area under curve (AUC) was 0.924(95%CI : 0.884-0.964), and sensitivity and specificity was 83.3% and 91.7%, respectively, which indicated that LINC00475 had good evaluation value in MM patients. Compared with low-LINC00475 expression group, patients in high-LINC00475 expression group had higher levels of ß2microglobulin (ß2-MG) and Cystatin C (Cys-C) but lower albumin (ALB) (all P < 0.05). Compared with MM patients with International Staging System (ISS) stage I, the expression level of LINC00475 was significantly higher in patients with stage II and III (both P < 0.05). CONCLUSION: LINC00475 is helpful to distinguish MM patients from healthy adults, which is correlated with the prognostic indicators such as ß2-MG, ALB, and ISS stage.

In situ HER2 RNA expression as a predictor of pathologic complete response of HER2-positive breast cancer patients receiving neoadjuvant chemotherapy and anti-HER2 targeted treatment.

BACKGROUND: Immunohistochemistry (IHC) and in situ hybridization (ISH) remain standard biomarkers for therapeutic decisions in human epidermal growth factor 2 (HER2)-positive breast cancers (BCs); however, they are insufficient to explain the heterogeneous anti-HER2 response. METHODS: We aimed to investigate the correlation of in situ HER2 RNA expression (isHRE), using RNAscope, with HER2 biomarkers and the impact of isHRE on the pathological complete response (pCR) rates of 278 patients with HER2 IHC/fluorescence ISH (FISH)-positive BC receiving neoadjuvant chemotherapy and anti-HER2 targeted treatment (NCTT). RESULTS: We validated HER2 RNAscope scoring as a semiquantitative method to determine isHRE and showed a positive correlation between RNAscope scores and pCR rates, with particularly different rates between patients with a score of 5 versus 1-4 BCs (66.7% vs. 15.9%, p < 0.0001). There were higher RNAscope scores and pCR rates in patients with HER2 IHC 3 + versus IHC 2+/FISH + BCs and HER2 RNAscope scores and pCR rates showed similar non-linear positive correlations with HER2 copy numbers and HER2/centromere 17 ratios. Moreover, in each HER2-positive IHC/FISH category, higher pCR rates were observed in patients with RNAscope scores of 5 versus 1-4 BC. Patients achieving pCR had BCs with notably higher HER2 RNAscope scores. Multivariate analysis identified HER2 RNAscope 5 as a strong pCR predictor [odds ratio = 10.865, p < 0.001]. The combined impact of multivariate analysis-defined pCR predictors demonstrated that a higher pCR rate was observed in patients with a score of 5 versus a score of 1-4 BCs regardless of the status of hormone receptor and mono-or dual anti-HER2 blockade. CONCUSIONS: Our results demonstrated that high isHRE (RNAscope score 5) is a strong pCR predictor in patients with HER2-positive BCs receiving NCTT, highlighting the complementary role of isHRE in stratifying HER2 status in tissue. Such stratification is relevant to anti-HER2 therapeutic efficacy, particularly using the cutoff of score 1-4 versus 5.

Gastric Section Correlation Network for Gastric Precancerous Lesion Diagnosis.

Goal: Diagnosing the corpus-predominant gastritis index (CGI) which is an early precancerous lesion in the stomach has been shown its effectiveness in identifying high gastric cancer risk patients for preventive healthcare. However, invasive biopsies and time-consuming pathological analysis are required for the CGI diagnosis. Methods: We propose a novel gastric section correlation network (GSCNet) for the CGI diagnosis from endoscopic images of three dominant gastric sections, the antrum, body and cardia. The proposed network consists of two dominant modules including the scaling feature fusion module and section correlation module. The front one aims to extract scaling fusion features which can effectively represent the mucosa under variant viewing angles and scale changes for each gastric section. The latter one aims to apply the medical prior knowledge with three section correlation losses to model the correlations of different gastric sections for the CGI diagnosis. Results: The proposed method outperforms competing deep learning methods and achieves high testing accuracy, sensitivity, and specificity of 0.957, 0.938 and 0.962, respectively. Conclusions: The proposed method is the first method to identify high gastric cancer risk patients with CGI from endoscopic images without invasive biopsies and time-consuming pathological analysis.

Advances in Synthesis and Applications of Single-Atom Catalysts for Metal Oxide-Based Gas Sensors.

As a stable, low-cost, environment-friendly, and gas-sensitive material, semiconductor metal oxides have been widely used for gas sensing. In the past few years, single-atom catalysts (SACs) have gained increasing attention in the field of gas sensing with the advantages of maximized atomic utilization and unique electronic and chemical properties and have successfully been applied to enhance the detection sensitivity and selectivity of metal oxide gas sensors. However, the application of SACs in gas sensors is still in its infancy. Herein, we critically review the recent advances and current status of single-atom catalysts in metal oxide gas sensors, providing some suggestions for the development of this field. The synthesis methods and characterization techniques of SAC-modified metal oxides are summarized. The interactions between SACs and metal oxides are crucial for the stable loading of single-atom catalysts and for improving gas-sensitive performance. Then, the current application progress of various SACs (Au, Pt, Cu, Ni, etc.) in metal oxide gas sensors is introduced. Finally, the challenges and perspectives of SACs in metal oxide gas sensors are presented.

Comparison of minimally invasive transforaminal lumbar interbody fusion and midline lumbar interbody fusion in patients with spondylolisthesis.

BACKGROUND: This study aimed to compare surgical outcomes, clinical outcomes, and complications between minimally invasive transforaminal lumbar interbody fusion (MIS TLIF) and midline lumbar interbody fusion (MIDLIF) in patients with spondylolisthesis. METHODS: This study retrospectively compared the patients who underwent MIS TLIF (n = 37) or MIDLIF (n = 50) for spinal spondylolisthesis. Data of surgical outcomes (postoperative one-year fusion rate and time to bony fusion), clinical outcomes (visual analog scale [VAS] for pain and Oswestry Disability Index [ODI] for spine function), and complications were collected and analyzed. RESULTS: There was more 2-level fusion in MIDLIF (46% vs. 24.3%, p = 0.038). The MIS TLIF and MIDLIF groups had similar one-year fusion rate and time to fusion. The MIDLIF group had significantly lower VAS at postoperative 3-months (2.2 vs. 3.1, p = 0.002) and postoperative 1-year (1.1 vs. 2.1, p = < 0.001). ODI was not significantly different. The operation time was shorter in MIDLIF (166.1 min vs. 196.2 min, p = 0.014). The facet joint violation is higher in MIS TLIF (21.6% vs. 2%, p = 0.009). The other complications were not significantly different including rate of implant removal, revision, and adjacent segment disease. CONCLUSION: In this study, postoperative VAS, operation time, and the rate of facet joint violation were significantly higher in the MIS TLIF group. Comparable outcomes were observed between MIDLIF and MIS TLIF in terms of fusion rate, time to fusion, and postoperative ODI score.

Lactobacillus Plantarum intake mitigates neuropathic pain behavior via enhancing macrophage M2 polarization in a rat model of peripheral neuropathy.

Pro-inflammatory macrophages (M1-polarized) play a crucial role in neuroinflammation and neuropathic pain following nerve injury. Redirecting macrophage polarization toward anti-inflammatory (M2-polarized) phenotypes offers a promising therapeutic strategy. Recognized for their anti-inflammatory and immunomodulatory properties, probiotics are becoming a focal point of research. This study investigated the effects of Lactobacillus plantarum on macrophage polarization, nerve protection, and neuropathic pain behavior following chronic constriction injury (CCI) of the median nerve. Rats received daily oral doses of L. plantarum for 28 days before and 14 days after CCI. Subsequently, behavioral and electrophysiological assessments were performed. The M1 marker CD86 levels, M2 marker CD206 levels, and concentrations of pro-inflammatory and anti-inflammatory cytokines in the injured median nerve were assessed. L. plantarum administration effectively reduced neuropathic pain behavior and the Firmicutes to Bacteroidetes ratio after CCI. Moreover, L. plantarum treatment increased serum short-chain fatty acids (SCFAs) levels, preserved myelination of the injured median nerve, and suppressed injury-induced discharges. In CCI rats treated with L. plantarum, there was a reduction in CD86 and pro-inflammatory cytokine levels, accompanied by an increase in CD206 and the release of anti-inflammatory cytokines. Furthermore, receptors for anti-inflammatory cytokines were localized on Schwann cells, and their expression was significantly upregulated in the injured nerves of CCI rats receiving L. plantarum. In conclusion, L. plantarum shifts macrophage phenotypes from M1 to M2 by promoting the production of SCFAs and enhancing the release of anti-inflammatory cytokines. Ultimately, this process preserves nerve fiber integrity and impedes the onset of neuropathic pain.

Wogonin ameliorates ER stress-associated inflammatory response, apoptotic death and renal fibrosis in a unilateral ureteral obstruction mouse model.

Wogonin, a vital bioactive compound extracted from the medicinal plant, Scutellaria baicalensis, has been wildly used for its potential in mitigating the progression of chronic diseases. Chronic kidney disease (CKD) represents a significant global health challenge due to its high prevalence, morbidity and mortality rates, and associated complications. This study aimed to assess the potential of wogonin in attenuating renal fibrosis and to elucidate the underlying molecular mechanisms using a unilateral ureteral obstruction (UUO) mouse model as a CKD mimic. Male mice, 8 weeks old, underwent orally administrated of either 50 mg/kg/day of wogonin or positive control of 5 mg/kg/day candesartan following UUO surgery. NRK52E cells were exposed to tumor growth factors-beta (TGF-ß) to evaluate the anti-fibrotic effects of wogonin. The results demonstrated that wogonin treatment effectively attenuated TGF-ß-induced fibrosis markers in NRK-52E cells. Additionally, administration of wogonin significantly improved histopathological alterations and downregulated the expression of pro-fibrotic factors (Fibronectin, α-smooth muscle actin, Collagen IV, E-cadherin, and TGF-ß), oxidative stress markers (Catalase, superoxide dismutase 2, NADPH oxidase 4, and thioredoxin reductase 1), inflammatory molecules (Cyclooxygenase-2 and TNF-α), and the infiltration of neutrophils and macrophages in UUO mice. Furthermore, wogonin treatment mitigated endoplasmic reticulum (ER) stress-associated molecular markers (GRP78, GRP94, ATF4, CHOP, and the caspase cascade) and suppressed apoptosis. The findings indicate that wogonin treatment ameliorates key fibrotic aspects of CKD by attenuating ER stress-related apoptosis, inflammation, and oxidative stress, suggesting its potential as a future therapeutic target.

Patient experience with bronchoscopy: topical versus monitored anesthesia.

BACKGROUND: This study aimed to compare patient experiences during bronchoscopy procedures using either topical anesthesia (TA) or monitored anesthesia care (MA). The goal was to identify circumstances where patients could achieve similar levels of tolerance and satisfaction using only TA, especially in resource-limited settings. METHODS: This study included consecutive patients who underwent bronchoscopy with either TA or MA. Data collected included demographics, indications for bronchoscopy, procedure time, and complications during the procedure. A quality assurance survey was administered to assess patient experience and satisfaction with both procedures. A pre-specified subgroup analysis was performed based on procedure invasiveness and time. RESULTS: This study enrolled 350 (TA 251; MA 99) patients, with an average age of 65 years. Main indications for bronchoscopy included tumor diagnosis (38%), esophageal cancer staging (18%), and pulmonary infection (17%). The average duration of the procedures was 20 min, with MA being associated with a significantly longer procedure time than TA (31 min vs. 16 min; P < 0.001). The overall satisfaction rating with bronchoscopy was significantly higher in the MA group (visual analogue scale, 8.9 vs. 8.2; P = 0.001). Subgroup analyses showed that when less invasive or shorter procedures were performed, TA patients reported tolerance and satisfaction levels comparable to MA patients. CONCLUSIONS: Bronchoscopy with MA offered patients a better experience and greater satisfaction; however, in settings with limited resources, TA alone may provide similar levels of patient tolerance and satisfaction during less invasive or shorter procedures.