Engineered Exosomes Complexed with Botulinum Toxin Type A for Enhanced Anti-Aging Effects on Skin.

Skin aging is commonly characterized by increased wrinkles, loss of elasticity, and hyperpigmentation, significantly affecting personal appearance and quality of life. Although botulinum toxin type A (BTX-A) has been widely applied in cosmetic anti-wrinkle treatments, its intrinsic cytotoxicity limits broader clinical applications. In this study, we developed a novel exosome-based BTX-A composite delivery system designed to synergize the anti-aging properties of exosomes with the wrinkle-reducing effects of BTX-A while reducing toxicity.

hUMSC-derived exosomes alleviate hypoxic cerebrovascular injury AMPK/NLRP3-mediated pyroptosis suppression and mitochondrial protection.

Ranked as the most prevalent cause of death worldwide, ischemic stroke urgently requires innovative therapeutic strategies. The present study demonstrates the therapeutic potential of human umbilical cord-derived mesenchymal stem cell-derived exosomes (hUMSC-Exos) in ameliorating hypoxia-induced cerebrovascular endothelial dysfunction through modulation of the AMPK/NLRP3 signaling pathway. Bioinformatics analysis of DisGeNET and exosomal cargo databases revealed 283 overlapping cerebral ischemia-related genes, implicating hUMSC-Exos in inflammatory regulation.

Elucidating molecular pathogenesis and developing targeted therapeutic interventions for cerebrovascular endothelial cell-mediated vascular dementia.

Vascular dementia (VaD) ranks as the second most prevalent subtype of dementia, surpassed only by Alzheimer's disease (AD). The maintenance of neurological function and cerebral homeostasis critically depends on precisely regulated blood flow within the intricately organized cerebrovascular network. Disruptions in cerebral hemodynamics may impair neurovascular homeostasis, thereby inducing pathophysiological cascades characterized by oxidative stress, neuroinflammation, and neuronal degeneration.

genetic variants drive autoimmune pathogenesis in multiple sclerosis and neuromyelitis optica spectrum disorders.

Objective: This study aims to investigate the association of Fc receptor-like 3 () gene variants with multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) in a Chinese population cohort.

Methods: In Stage 1, 154 MS patients, 109 NMOSD patients, and 301 normal controls were recruited, Sequenom MassARRAY technology was used for genotyping single nucleotide polymorphisms (SNPs). Stage 2 involved an independent cohort of 95 MS patients, 139 NMOSD patients, and 226 normal controls.

Mechanism of Endothelial Cell Death in Cerebral Ischemic Stroke and Application of Protective Drugs.

Brain endothelial cells (BECs) are situated at the interface between the bloodstream and the brain, serving a crucial function in the development and maturation of the brain, particularly in upholding the integrity of the blood-brain barrier (BBB). Consequently, any modifications or gradual breakdown of the endothelium can significantly disrupt brain homeostasis. Ischemic stroke (IS), characterized by the progressive compromise of the BBB and increased BECs mortality, stands as a prominent global cause of mortality and disability.

Epigenetic regulation and tumor suppressive function of lncRNA EP300-AS1 in nasopharyngeal carcinoma through activation of TFAP2C binding to CST6: implications for diagnosis, prognosis, and therapy.

The long non-coding RNA EP300-AS1 (lncRNA EP300-AS1), identified as a potential regulatory factor in various cancers, remains underexplored in nasopharyngeal carcinoma (NPC). This study investigated EP300-AS1's regulatory mechanisms in NPC, particularly its interaction with transcription factor AP-2 Gamma (TFAP2C) and its effect on cystatin E/M (CST6) expression. Employing clinical samples and NPC cell lines, we conducted in vitro and in vivo xenograft experiments to assess the impacts of modulating EP300-AS1 expression.

SKA3 promotes lung adenocarcinoma progression via the EGFR/E2F1/SKA3/integrin β1 signaling loop.

Spindle and kinetochore-associated complex subunit 3 (SKA3) contributes to tumor growth and metastasis, but its specific roles have not been clearly elucidated. In this study, we found that SKA3 contributed to lung adenocarcinoma (LUAD) progression by interacting with integrin β1. The expression characteristics of SKA3 in LUAD patients were analyzed by The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets and validated in 33 paired LUAD tissues by immunohistochemistry.

An environmentally sensitive zinc-selective two-photon NIR fluorescent turn-on probe and zinc sensing in stroke.

A two-photon near infrared (NIR) fluorescence turn-on sensor with high selectivity and sensitivity for Zn detection has been developed. This sensor exhibits a large Stokes' shift (∼300 nm) and can be excited from 900 to 1000 nm, with an emission wavelength of ∼785 nm, making it ideal for imaging in biological tissues. The sensor's high selectivity for Zn over other structurally similar cations, such as Cd, makes it a promising tool for monitoring zinc ion levels in biological systems.

Regulation of the AGEs-induced inflammatory response in human periodontal ligament cells via the AMPK/NF-κB/ NLRP3 signaling pathway.

The heightened prevalence and accelerated progression of periodontitis in individuals with diabetes is primarily attributed to inflammatory responses in human periodontal ligament cells (HPDLCs). This study is aimed at delineating the regulatory mechanism of nucleotide-binding oligomerization domain-like receptors (NLRs) in mediating inflammation incited by muramyl dipeptide (MDP) in HPDLCs, under the influence of advanced glycation end products (AGEs), metabolic by-products associated with diabetes. We performed RNA-seq in HPDLCs induced by AGEs treatment and delineated activation markers for the receptor of AGEs (RAGE).

GPR124 induces NLRP3 inflammasome-mediated pyroptosis in endothelial cells during ischemic injury.

Objective: G protein-coupled receptor 124 (GPR124) regulates central nervous system angiogenesis and blood-brain barrier (BBB) integrity, and its deficiency aggravates BBB breakdown and hemorrhagic transformation in ischemic mice. However, excessive GPR124 expression promotes inflammation in atherosclerotic mice. In this study, we aimed to elucidate the role of GPR124 in hypoxia/ischemia-induced cerebrovascular endothelial cell injury.

Safety and Effectiveness of High-dose Liposomal Amphotericin B: A Systematic Review and Meta-analysis.

Background: Although the level of medical care has been improved in recent years, the probability of patients contracting pathogens has increased greatly, with a rising incidence of invasive fungal infections. Deep-seated fungi have become common pathogens of nosocomial infections.

Objective: This study aims to systematically assess the effectiveness, mortality, survival rate, and adverse reactions (ARs) of high-dose (HD) liposomal amphotericin B (L-AMB) for human diseases.

Oligodendrocytes Play a Critical Role in White Matter Damage of Vascular Dementia.

With the deepening of population aging, the treatment of cognitive impairment and dementia is facing increasing challenges. Vascular dementia (VaD) is a cognitive dysfunction caused by brain blood flow damage and one of the most common causes of dementia after Alzheimer's disease. White matter damage in patients with chronic ischemic dementia often occurs before cognitive impairment, and its pathological changes include leukoaraiosis, myelin destruction and oligodendrocyte death.

Human embryonic stem cells secrete macrophage migration inhibitory factor: A novel finding.

Macrophage migration inhibitory factor (MIF) is expressed in a variety of cells and participates in important biological mechanisms. However, few studies have reported whether MIF is expressed in human Embryonic stem cells (ESCs) and its effect on human ESCs. Two human ESCs cell lines, H1 and H9 were used.

The overexpression and clinical significance of TBX15 in human gliomas.

T-box transcription factor 15 (TBX15) is upregulated in a variety of tumors and has been reported to promote uncontrolled proliferation of tumor cells and induce tumor cells to avoid apoptosis, thus accelerating the malignant transformation of malignant tumors. However, the prognostic value of TBX15 in glioma and its relationship with immune infiltration remain unknown. In this study, we intended to explore the prognostic value of TBX15 and its link to glioma immune infiltration and examine TBX15 expression in pan-cancer using RNAseq data in TPM format from TCGA and GTEx.

Advances in immunotherapy modalities for atherosclerosis.

Cardiovascular disease (CVD) is one of the leading causes of death worldwide. Atherosclerosis is the pathological basis of atherosclerotic cardiovascular disease (ASCVD). Atherosclerosis is now understood to be a long-term immune-mediated inflammatory condition brought on by a complicated chain of factors, including endothelial dysfunction, lipid deposits in the artery wall, and monocyte-derived macrophage infiltration, in which both innate immunity and adaptive immunity play an indispensable role.

Polysaccharides from Lam. (jackfruit) pulp improves intestinal barrier functions of high fat diet-induced obese rats.

Polysaccharides show protective effects on intestinal barrier function due to their effectiveness in mitigating oxidative damage, inflammation and probiotic effects. Little has been known about the effects of polysaccharides from Lam. pulp (jackfruit, JFP-Ps) on intestinal barrier function.

A Novel Strategy for Alzheimer's Disease Based on the Regulatory Effect of Amyloid-β on Gut Flora.

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases worldwide. The accumulation of amyloid-β (Aβ) protein and plaque formation in the brain are two major causes of AD. Interestingly, growing evidence demonstrates that the gut flora can alleviate AD by affecting amyloid production and metabolism.

Targeting 4-1BB for tumor immunotherapy from bench to bedside.

Immune dysfunction has been proposed as a factor that may contribute to disease progression. Emerging evidence suggests that immunotherapy aims to abolish cancer progression by modulating the balance of the tumor microenvironment. 4-1BB (also known as CD137 and TNFRS9), a member of tumor necrosis factor receptor superfamily, has been validated as an extremely attractive and promising target for immunotherapy due to the upregulated expression in the tumor environment and its involvement in tumor progression.

TLR9/FCRL3 regulates B cell viability, apoptosis, and antibody and IL-10 production through ERK1/2, p38, and STAT3 signaling pathways.

B cells play a role in the progression of multiple sclerosis (MS) and are closely related to Fc-receptor like-3 (FCRL3), but little is known about FCRL3 in B cells and MS. Activation of TLR9 in B cells with CpG found that CpG promoted FCRL3 expression in a dose- and time-dependent manner. CpG significantly activated ERK1/2, p38, and STAT3 pathways, and FCRL3 overexpression further promoted the activation of these pathways, while FCRL3 siRNA significantly inhibited the activation of these pathways by CpG.

Advances in Immune Microenvironment and Immunotherapy of Isocitrate Dehydrogenase Mutated Glioma.

The tumor immune microenvironment and immunotherapy have become current important tumor research concerns. The unique immune microenvironment plays a crucial role in the malignant progression of isocitrate dehydrogenase (IDH) mutant gliomas. IDH mutations in glioma can inhibit tumor-associated immune system evasion of NK cell immune surveillance.

Discovery of Novel Quinazoline Derivatives as Potent Antitumor Agents.

In this work, we designed and synthesized a novel series of quinazoline derivatives - and then evaluated their broad-spectrum antitumor activity against MGC-803, MCF-7, PC-9, A549, and H1975, respectively. Most of them demonstrated low micromolar cytotoxicity towards five tested cell lines. In particular, compound exhibited nanomolar level inhibitory activity against MGC-803 cells with an IC value of 0.