Topical application of a BCL-2 inhibitor ameliorates imiquimod-induced psoriasiform dermatitis by eliminating senescent cells.

BACKGROUND: Psoriasis is an inflammatory skin disease with unclear pathogenesis and unmet therapeutic needs. OBJECTIVE: To investigate the role of senescent CD4+ T cells in psoriatic lesion formation and explore the application of senolytics in treating psoriasis. METHODS: We explored the expression levels of p16INK4a and p21, classical markers of cellular senescence, in CD4+ T cells from human psoriatic lesions and imiquimod (IMQ)-induced psoriatic lesions. We prepared a senolytic gel using B-cell lymphoma 2 (BCL-2) inhibitor ABT-737 and evaluated its therapeutic efficacy in treating psoriasis. RESULTS: Using multispectrum immunohistochemistry (mIHC) staining, we detected increased expression levels of p16INK4a and p21 in CD4+ T cells from psoriatic lesions. After topical application of ABT-737 gel, significant alleviation of IMQ-induced psoriatic lesions was observed, with milder pathological alterations. Mechanistically, ABT-737 gel significantly decreased the percentage of senescent cells, expression of T cell receptor (TCR) α and ß chains, and expression of Tet methylcytosine dioxygenase 2 (Tet2) in IMQ-induced psoriatic lesions, as determined by mIHC, high-throughput sequencing of the TCR repertoire, and RT-qPCR, respectively. Furthermore, the severity of psoriatic lesions in CD4creTet2f/f mice was milder than that in Tet2f/f mice in the IMQ-induced psoriasis model. CONCLUSION: We revealed the roles of senescent CD4+ T cells in developing psoriasis and highlighted the therapeutic potential of topical ABT-737 gel in treating psoriasis through the elimination of senescent cells, modulation of the TCR αß repertoire, and regulation of the TET2-Th17 cell pathway.

Investigation on the contaminate of hand washing activities on the surface of environmental objects in intensive care unit.

To detect the contaminate of faucets in hospitals and the splash during hand washing, and to explore the reasonable layout of hand washing pools. Two faucets with roughly the same spatial layout in the ICU of a third-class first-class general hospital were selected, and the farthest splashing distance and specific splashing points were measured by color paper. Samples were detected by ATP detection technology and routine microbial detection method, and the contaminate of faucets was analyzed. After 72 h of daily hand-washing activities, the furthest distance to the splash point was about 100 cm around the faucet, and the place 40-110 cm around the faucet was contaminated seriously. The farthest distance that the splash point reached was about 80 cm around the faucet with the center of the circle, and the area 40-60 cm around the faucet was heavily contaminated. The distance from the water outlet of the long handle and the short handle faucet to the detection point had a high negative correlation (r = - 0.811, P < 0.001) and a moderate negative correlation (r = - 0.475, P = 0.001) with the number of splash points, respectively. The qualified rates of ATP detection and microbial culture were 25% and 15%, respectively. Pseudomonas aeruginosa, Staphylococcus epidermidis, and other pathogenic bacteria were detected in the water outlet of the faucet and the surrounding environment. Safe hand hygiene facilities are one of the important guarantees of hand hygiene effect. Clean objects and objects related to patients should not be placed within 1 m range near the water outlet of faucet. Anti-splash baffle should be installed as much as possible when conditions permit to reduce the contaminate caused by splash during hand washing.

PRRX1-fused mesenchymal neoplasm: A novel PRRX1::NCOA1 fusion transcript.

PRRX1-fused mesenchymal neoplasm is a recently identified, rare subcutaneous soft tissue neoplasm that is characterized by fusion of PRRX1 (exon 1) with NCOA1 (exon 13) in the majority of reported cases. Although initially considered to be fibroblastic, a possibility of neural or neuroectodermal differentiation has been suggested in a subset of cases. We report a 26-year-old female with a 4.0 cm painless mass located in the subcutis of the left thigh. Microscopically, the tumor was well-circumscribed and multinodular and was composed of relatively monomorphic ovoid to spindle cells arranged in loose fascicles, trabeculae, and cords within alternating myxoid and fibrous matrix, and vascularized stroma. Mitotic figures were scarce and necrosis was not observed. By immunohistochemistry, the neoplastic cells demonstrated focal co-expression of S100 protein and SOX10 and were negative for epithelial membrane antigen, smooth muscle actin, desmin, CD34, STAT6, HMB45, Melan-A, and MUC4. The expression of Rb1 was retained. Targeted RNA-sequencing identified a novel transcript fusion of PRRX1 (exon 1)::NCOA1 (exon 15), which was further confirmed by reverse transcription polymerase chain reaction and Sanger sequencing. The tumor was narrowly excised and no tumor recurrence or metastasis was identified after 13 months of follow-up. In summary, we report a new case of PRRX1-fused mesenchymal neoplasm, expanding the molecular genetic spectrum and providing further support for possible neural or neuroectodermal differentiation of this emerging soft tissue tumor entity.

[Lysine Succinylation:A New Perspective in the Treatment of Cardiovascular Diseases].

With the continuous development of identification technologies such as mass spectrometry,omics,and antibody technology,post-translational modification (PTM) has demonstrated increasing potential in medical research.PTM as a novel chemical modification method provides new perspectives for the research on diseases.Succinylation as a novel modification has aroused the interest of more and more researchers.The available studies about succinylation mainly focus on a desuccinylase named sirtuin 5.This enzyme plays a key role in modification and has been preliminarily explored in cardiovascular studies.This paper summarizes the influencing factors and regulatory roles of succinylation and the links between succinylation and other PTMs and reviews the research progress of PTMs in the cardiovascular field,aiming to deepen the understanding about the role of this modification and give new insights to the research in this field.

A Planar-Structured Dinuclear Cobalt(II) Complex with Indirect Synergy for Photocatalytic CO2-to-CO Conversion.

Dinuclear metal synergistic catalysis (DMSC) has been proved an effective approach to enhance catalytic efficiency in photocatalytic CO2 reduction reaction, while it remains challenge to design dinuclear metal complexes that can show DMSC effect. The main reason is that the influence of the microenvironment around dinuclear metal centres on catalytic activity has not been well recognized and revealed. Herein, we report a dinuclear cobalt complex featuring a planar structure, which displays outstanding catalytic efficiency for photochemical CO2-to-CO conversion. The turnover number (TON) and turnover frequency (TOF) values reach as high as 14457 and 0.40 s-1 respectively, 8.6 times higher than those of the corresponding mononuclear cobalt complex. Control experiments and DFT calculations revealed that the enhanced catalytic efficiency of the dinuclear cobalt complex is due to the indirect DMSC effect between two CoII ions, energetically feasible one step two-electron transfer process by Co2I,I intermediate to afford Co2II,II(CO22-) intermediate and fast mass transfer closely related with the planar structure.

Measurable residual disease testing by next generation sequencing is more accurate compared with multiparameter flow cytometry in adults with B-cell acute lymphoblastic leukemia.

Results of measurable residual disease (MRD)-testing by next-generation sequencing (NGS) correlate with relapse risk in adults with B-cell acute lymphoblastic leukemia (ALL) receiving chemotherapy or an allotransplant from a human leukocyte antigen (HLA)-identical relative or HLA-matched unrelated donor. We studied cumulative incidence of relapse (CIR) and survival prediction accuracy using a NGS-based MRD-assay targeting immunoglobulin genes after 2 courses of consolidation chemotherapy cycles in 93 adults with B-cell ALL most receiving HLA-haplotype-matched related transplants. Prediction accuracy was compared with MRD-testing using multi-parameter flow cytometry (MPFC). NGS-based MRD-testing detected residual leukemia in 28 of 65 subjects with a negative MPFC-based MRD-test. In Cox regression multi-variable analyses subjects with a positive NGS-based MRD-test had a higher 3-year CIR (Hazard Ratio [HR] = 3.37; 95 % Confidence Interval [CI], 1.34-8.5; P = 0.01) and worse survival (HR = 4.87 [1.53-15.53]; P = 0.007). Some data suggest a lower CIR and better survival in NGS-MRD-test-positive transplant recipients but allocation to transplant was not random. Our data indicate MRD-testing by NGS is more accurate compared with testing by MPFC in adults with B-cell ALL in predicting CIR and survival. (Registered in the Beijing Municipal Health Bureau Registration N 2007-1007 and in the Chinese Clinical Trial Registry [ChiCTR-OCH-10000940 and ChiCTROPC-14005546]).

Physicochemical and Rheological Properties of Degraded Konjac Gum by Abalone (Haliotis discus hannai) Viscera Enzyme.

In the present study, a new degraded konjac glucomannan (DKGM) was prepared using a crude enzyme from abalone (Haliotis discus hannai) viscera, and its physicochemical properties were investigated. After enzymatic hydrolysis, the viscosity of KGM obviously decreased from 15,500 mPa·s to 398 mPa·s. The rheological properties analysis of KGM and DKGMs revealed that they were pseudoplastic fluids, and pseudoplasticity, viscoelasticity, melting temperature, and gelling temperature significantly decreased after enzymatic hydrolysis, especially for KGM-180 and KGM-240. In addition, the molecular weight of KGM decreased from 1.80 × 106 Da, to 0.45 × 106 Da and the polydispersity index increased from 1.17 to 1.83 after 240 min of degradation time. Compared with natural KGM, the smaller particle size distribution of DKGM further suggests enzyme hydrolysis reduces the aggregation of molecular chains with low molecular weight. FT-IR and FESEM analyses showed that the fragmented KMG chain did not affect the structural characteristics of molecular monomers; however, the dense three-dimensional network microstructure formed by intermolecular interaction changed to fragment microstructure after enzyme hydrolysis. These results revealed that the viscosity and rheological properties of KGM could be controlled and effectively changed using crude enzymes from abalone viscera. This work provides theoretical guidance for the promising application of DKGM in the food industry.

Genetic deletion or pharmacologic inhibition of HDAC6 protects the heart against ischemia/reperfusion injury by limiting TNFα-induced mitochondrial injury in experimental diabetes.

AIMS: The histone deacetylase 6 (HDAC6) inhibitor, tubastatin A, reduces myocardial ischemia/reperfusion injury (MIRI) in type 1 diabetic rats. It remains unclear whether HDAC6 regulates MIRI in type 2 diabetic animals. Diabetes augments activity of HDAC6 and generation of tumor necrosis factor α (TNFα) and impairs mitochondrial complex I (mCI). Here we examined how HDAC6 regulates TNFα production, mCI activity, mitochondria, and cardiac function in type 1 and type 2 diabetic mice undergoing MIRI. METHODS AND RESULTS: HDAC6 knockout, streptozotocin-induced type 1 diabetic, and obese type 2 diabetic db/db mice underwent MIRI in vivo or ex vivo in a Langendorff-perfused system. We found that MIRI and diabetes additively augmented myocardial HDAC6 activity and generation of TNFα, along with cardiac mitochondrial fission, low bioactivity of mCI, and low production of ATP. Importantly, genetic disruption of HDAC6 or tubastatin A decreased TNFα levels, mitochondrial fission, and myocardial mitochondrial NADH levels in ischemic/reperfused diabetic mice, concomitant with augmented mCI activity, decreased infarct size, and improved cardiac function. Moreover, HDAC6 knockout or tubastatin A treatment decreased left ventricular dilation and improved cardiac systolic function 28 days after MIRI. H9c2 cardiomyocytes with and without HDAC6 knockdown were subjected to hypoxia/reoxygenation injury in the presence of high glucose. Hypoxia/reoxygenation augmented HDAC6 activity and TNFα levels and decreased mCI activity. These negative effects were blocked by HDAC6 knockdown. CONCLUSIONS: HDAC6 is an essential negative regulator of MIRI in diabetes. Genetic deletion or pharmacologic inhibition of HDAC6 protects the heart from MIRI by limiting TNFα-induced mitochondrial injury in experimental diabetes.

One-to-Nine Single Spectroscopic Intelligent Probe for Risk Assessment of Multiple Metals in Drinking Water.

26% of the world's population lacks access to clean drinking water; clean water and sanitation are major global challenges highlighted by the UN Sustainable Development Goals, indicating water security in public water systems is at stake today. Water monitoring using precise instruments by skilled operators is one of the most promising solutions. Despite decades of research, the professionalism-convenience trade-off when monitoring ubiquitous metal ions remains the major challenge for public water safety. Thus, to overcome these disadvantages, an easy-to-use and highly sensitive visual method is desirable. Herein, an innovative strategy for one-to-nine metal detection is proposed, in which a novel thiourea spectroscopic probe with high 9-metal affinity is synthesized, acting as "one", and is detected based on the 9 metal-thiourea complexes within portable spectrometers in the public water field; this is accomplished by nonspecialized personnel as is also required. During the processing of multimetal analysis, issues arise due to signal overlap and reproducibility problems, leading to constrained sensitivity. In this innovative endeavor, machine learning (ML) algorithms were employed to extract key features from the composite spectral signature, addressing multipeak overlap, and completing the detection within 30-300 s, thus achieving a detection limit of 0.01 mg/L and meeting established conventional water quality standards. This method provides a convenient approach for public drinking water safety testing.

Two new Cortinarius species in subgenus Leprocybe from Southwest China.

Two new Cortinarius species in subgenus Leprocybe, Cortinarius hengduanensis and C. yadingensis, are proposed based on a combination of morphological and molecular evidence. Cortinarius hengduanensis has distinct olive tinged basidiomata, a squamulose pileus, and small, subglobose to broadly ellipsoid basidiospores, the ITS sequence differs from that of C. flavifolium by at least 28 substitutions and independent positions. Cortinarius yadingensis has a squamulose pileus and subglobose to broadly ellipsoid coarsely verrucose basidiospores, the ITS sequence has at least 11 substitutions and index position deviations from the other members of the Leprocybe section. Both new species were found in mixed forests of southwest China.

Development of a highly sensitive ultra-small ratiometric fluorescence nanosphere probe for Sunset Yellow detection.

A highly sensitive ultra-small ratiometric fluorescence nanosphere probe was successfully manufactured to detect Sunset Yellow (SY). The probe, CMCS@N, S-CDs/Rh6G, was formed through the encapsulation of N, S-CDs and Rh6G within carboxymethyl chitosan (CMCS) through in situ cross-linking. Remarkably, our nanosphere probe had an average grain diameter of 6.80 nm and exhibited excellent dispersibility without the need for additional solvents. The probe exhibited a strong linear relationship with SY concentration in the range of 0.26-100 µM, with a low detection limit of 0.078 µM. Furthermore, SY demonstrated strong fluorescence quenching capability on our nanosphere probe, with the fluorescence quenching mechanism involving a combined effects of inner filter effect (IFE) and static quenching. Notably, our nanosphere probe retained the bacteriostatic properties of CMCS, with a substantial bacteriostasis rate of 77.58 %, introducing novel potential applications.

Fresnel lens three-dimensionally printed on the facet of a single mode fiber for trapping, manipulation, and spectrum.

Fiber optical tweezers (FOTs) provide a functionality for micro-/nanoparticle manipulation with a slim and flexible optical fiber setup. An added in situ spectroscopic functionality can achieve characterization of the trapped particle, potentially useful for endoscopic, in-vivo studies in an inherently heterogeneous environment if the applicator end is all-fiber-built. Here, we demonstrate all-fiber optical tweezers (a-FOTs) for the trapping and in situ spectral measurement of a single, cell-sized microparticle. The key to ensure the simultaneous bifunctionality is a high numerical aperture (NA) Fresnel lens fabricated by two-photon direct laser writing (DLW) corrected by grid-correction methods. We demonstrate trapping and time-resolved, in situ spectroscopy of a single upconversion particle (UCP), a common fluorescent biomarker in biophotonics. The system achieves a 0.5-s time resolution in the in situ spectral measurement of a trapped UCP. The all-fiber designed system preserves the advantages of flexibility and robustness of the fiber, potentially useful for in-vivo biomedical studies such as cell-to-cell interactions, pH and temperature detection, and nucleic acids detection.

Monolayer directional metasurface for all-optical image classifier doublet: publisher's note.

This publisher's note contains a correction to Opt. Lett.49, 2505 (2024)10.1364/OL.520642.

FTY720 ameliorates experimental MPO-ANCA-associated vasculitis by regulating fatty acid oxidation via the neutrophil PPARα-CPT1a pathway.

OBJECTIVES: Increasing studies demonstrated the importance of C5a and anti-neutrophil cytoplasmic antibody (ANCA)-induced neutrophil activation in the pathogenesis of ANCA-associated vasculitis (AAV). Sphingosine-1-phosphate (S1P) acts as a downstream effector molecule of C5a and enhances neutrophil activation induced by C5a and ANCA. The current study investigated the role of a S1P receptor modulator FTY720 in experimental autoimmune vasculitis (EAV) and explored the immunometabolism-related mechanisms of FTY720 in modulating ANCA-induced neutrophil activation. METHODS: The effects of FTY720 in EAV were evaluated by quantifying hematuria, proteinuria, crescent formation, tubulointerstitial injury and pulmonary hemorrhage. RNA sequencing of renal cortex and gene enrichment analysis were performed. The proteins of key identified pathways were analyzed in neutrophils isolated from peripheral blood of patients with active AAV and normal controls. We assessed the effects of FTY720 on ANCA-induced neutrophil respiratory burst and neutrophil extracellular traps formation (NETosis). RESULTS: FTY720 treatment significantly attenuated renal injury and pulmonary hemorrhage in EAV. RNA sequencing analyses of renal cortex demonstrated enhanced fatty acid oxidation (FAO) and peroxisome proliferators-activated receptors (PPAR) signalling in FTY720-treated rats. Compared with normal controls, patients with active AAV showed decreased FAO in neutrophils. FTY720-treated differentiated HL-60 cells showed increased expression of carnitine palmitoyltransferase 1A (CPT1a) and PPARα. Blocking or knockdown of CPT1a or PPARα in isolated human neutrophils and HL-60 cells reversed the inhibitory effects of FTY720 on ANCA-induced neutrophil respiratory burst and NETosis. CONCLUSION: FTY720 attenuated renal injury in EAV through upregulating FAO via the PPARα-CPT1a pathway in neutrophils, offering potential immunometabolic targets in AAV treatment.

Brain Short-Chain Fatty Acids Induce ACSS2 to Ameliorate Depressive-Like Behavior via PPARγ-TPH2 Axis.

Short-chain fatty acids (SCFAs) have been increasingly evidenced to be important bioactive metabolites of the gut microbiota and transducers in controlling diverse psychiatric or neurological disorders via the microbiota-gut-brain axis. However, the precise mechanism by which brain SCFAs extert multiple beneficial effects is not completely understood. Our previous research has demonstrated that the acetyl-coenzyme A synthetase short-chain family member 2 (ACSS2) is a novel target of the rapid and long-lasting antidepressant responses. Here, we show that micromolar SCFAs significantly augment both total cellular and nuclear ACSS2 to trigger tryptophan hydroxylase 2 (TPH2) promoter histone acetylation and its transcription in SH-SY5Y cells. In chronic-restraint-stress-induced depression mice, neuronal ACSS2 knockdown by stereotaxic injection of adeno-associated virus in the hippocampus abolished SCFA-mediated improvements in depressive-like behaviors of mice, supporting that ACSS2 is required for SCFA-mediated antidepressant responses. Mechanistically, the peroxisome-proliferator-activated receptor gamma (PPARγ) is identified as a novel partner of ACSS2 to activate TPH2 transcription. Importantly, PPARγ is also responsible for SCFA-mediated antidepressant-like effects via ACSS2-TPH2 axis. To further support brain SCFAs as a therapeutic target for antidepressant effects, d-mannose, which is a naturally present hexose, can significantly reverse the dysbiosis of gut microbiota in the chronic-restraint-stress-exposure mice and augment brain SCFAs to protect against the depressive-like behaviors via ACSS2-PPARγ-TPH2 axis. In summary, brain SCFAs can activate ACSS2-PPARγ-TPH2 axis to play the antidepressive-like effects, and d-mannose is suggested to be an inducer of brain SCFAs in resisting depression.

ALK-Rearranged Renal Cell Carcinoma: A Multi-Institutional Study of 9 Cases With Expanding the Morphologic and Molecular Genetic Spectrum.

ALK-rearranged renal cell carcinoma (ALK-RCC) is rare, molecularly defined RCC subtype in the recently published fifth edition of World Health Organization classification of tumors. In this study, we described 9 ALK-RCCs from a clinicopathologic, immunohistochemical, and molecular genetic aspect, supporting and extending upon the observations by previous studies regarding this rare subgroup of RCC. There were 6 male and 3 female patients with ages ranging from 14 to 59 years (mean, 34.4 years). None of the patients had sickle cell trait. The diagnosis was based on radical or partial nephrectomy specimen for 8 patients and on biopsy specimen for 1. Tumor size ranged from 2.5 to 7.2 cm (mean, 2.8 cm). Follow-up was available for 6 of 9 patients (6-36 months); 5 had no tumor recurrence or metastasis and 1 developed lung metastasis at 24 months. The patient was subsequently treated with resection of the metastatic tumor followed by crizotinib-targeted therapy, and he was alive without tumor 12 months later. Histologically, the tumors showed a mixed growth of multiple patterns, including papillary, solid, tubular, tubulocystic, cribriform, and corded, often set in a mucinous background. The neoplastic cells had predominantly eosinophilic cytoplasm. Focally, clear cytoplasm with polarized nuclei and subnuclear vacuoles (n = 1), and pale foamy cytoplasm (n = 1) were observed on the tumor cells. The biopsied tumor showed solid growth of elongated tubules merging with bland spindle cells. Other common and uncommon features included psammomatous microcalcifications (n = 5), rhabdoid cells (n = 4), prominent intracytoplasmic vacuoles (n = 4), prominent chronic inflammatory infiltrate (n = 3), signet ring cell morphology (n = 2), and pleomorphic cells (n = 2). By immunohistochemistry, all 9 tumors were diffusely positive for ALK(5A4) and 4 of 8 tested cases showed reactivity for TFE3 protein. By fluorescence in situ hybridization analysis, ALK rearrangement was identified in all the 9 tumors; none of the tested tumors harbored TFE3 rearrangement (0/4) or gains of chromosomes 7 and 17 (0/3). ALK fusion partners were identified by RNA-sequencing in all 8 cases analyzed, including EML4 (n = 2), STRN (n = 1), TPM3 (n = 1), KIF5B (n = 1), HOOK1 (n = 1), SLIT1 (n = 1), and TPM1(3'UTR) (n = 1). Our study further expands the morphologic and molecular genetic spectrum of ALK-RCC.

N-terminal truncated phospholipase A1 accessory protein PlaS from Serratia marcescens alleviates inhibitory on host cell growth and enhances PlaA1 enzymatic activity.

Phospholipase A1 (PLA1) is a kind of specific phospholipid hydrolase widely used in food, medical, textile. However, limitations in its expression and enzymatic activity have prompted the investigation of the phospholipase-assisting protein PlaS. In this study, we elucidate the role of PlaS in enhancing the expression and activity of PlaA1 through N-terminal truncation. Our research demonstrates that truncating the N-terminal region of PlaS effectively overcomes its inhibitory effect on host cells, resulting in improved cell growth and increased protein solubility of the protein. The yeast two-hybrid assay confirms the interaction between PlaA1 and N-terminal truncated PlaS (∆N27 PlaS), highlighting their binding capabilities. Furthermore, in vitro studies using Biacore analysis reveal a concentration-dependent and specific binding between PlaA1 and ∆N27 PlaS, exhibiting high affinity. Molecular docking analysis provides insights into the hydrogen bond interactions between ∆N27 PlaS and PlaA1, identifying key amino acid residues crucial for their binding. Finally, the enzyme activity of PLA1 was boost to 8.4 U/mL by orthogonal test. Study significantly contributes to the understanding of the interaction mechanism between PlaS and PlaA1, offering potential strategies for enhancing PlaA1 activity through protein engineering approaches.

Fibroblast: A Novel Target for Autoimmune and Inflammatory Skin Diseases Therapeutics.

Fibroblasts are crucial components of the skin structure. They were traditionally believed to maintain the skin's structure by producing extracellular matrix and other elements. Recent research illuminated that fibroblasts can respond to external stimuli and exhibit diverse functions, such as the secretion of pro-inflammatory factors, adipogenesis, and antigen presentation, exhibiting remarkable heterogeneity and plasticity. This revelation positions fibroblasts as active contributors to the pathogenesis of skin diseases, challenging the traditional perspective that views fibroblasts solely as structural entities. Based on their diverse functions, fibroblasts can be categorized into six subtypes: pro-inflammatory fibroblasts, myofibroblasts, adipogenic fibroblasts, angiogenic fibroblasts, mesenchymal fibroblasts, and antigen-presenting fibroblasts. Cytokines, metabolism, and epigenetics regulate functional abnormalities in fibroblasts. The dynamic changes fibroblasts exhibit in different diseases and disease states warrant a comprehensive discussion. We focus on dermal fibroblasts' aberrant manifestations and pivotal roles in inflammatory and autoimmune skin diseases, including psoriasis, vitiligo, lupus erythematosus, scleroderma, and atopic dermatitis, and propose targeting aberrantly activated fibroblasts as a potential therapeutic strategy for inflammatory and autoimmune skin diseases.

Crosstalk among Oxidative Stress, Autophagy, and Apoptosis in the Protective Effects of Ginsenoside Rb1 on Brain Microvascular Endothelial Cells: A Mixed Computational and Experimental Study.

OBJECTIVE: Brain microvascular endothelial cells (BMECs) were found to shift from their usually inactive state to an active state in ischemic stroke (IS) and cause neuronal damage. Ginsenoside Rb1 (GRb1), a component derived from medicinal plants, is known for its pharmacological benefits in IS, but its protective effects on BMECs have yet to be explored. This study aimed to investigate the potential protective effects of GRb1 on BMECs. METHODS: An in vitro oxygen-glucose deprivation/reperfusion (OGD/R) model was established to mimic ischemia-reperfusion (I/R) injury. Bulk RNA-sequencing data were analyzed by using the Human Autophagy Database and various bioinformatic tools, including gene set enrichment analysis (GSEA), Gene Ontology (GO) classification and enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, protein-protein interaction network analysis, and molecular docking. Experimental validation was also performed to ensure the reliability of our findings. RESULTS: Rb1 had a protective effect on BMECs subjected to OGD/R injury. Specifically, GRb1 was found to modulate the interplay between oxidative stress, apoptosis, and autophagy in BMECs. Key targets such as sequestosome 1 (SQSTM1/p62), autophagy related 5 (ATG5), and hypoxia-inducible factor 1-alpha (HIF-1α) were identified, highlighting their potential roles in mediating the protective effects of GRb1 against IS-induced damage. CONCLUSION: GRbl protects BMECs against OGD/R injury by influencing oxidative stress, apoptosis, and autophagy. The identification of SQSTM1/p62, ATG5, and HIF-1α as promising targets further supports the potential of GRb1 as a therapeutic agent for IS, providing a foundation for future research into its mechanisms and applications in IS treatment.