Advanced biology最新文献

Ischemic heart disease, a leading global cause of mortality, highlights the need for novel therapies. Electroacupuncture (EA) shows cardioprotective potential, yet the central neural mechanisms, particularly the role of the midbrain periaqueductal gray (PAG), remain unclear. This study investigated how EA at Shen men (HT7) improves cardiac function post-myocardial infarction (MI) via Ventrolateral Periaqueductal Gray Matter (vlPAG) glutamatergic(Glu) neurons. Neuronal activity monitored via c-Fos immunofluorescence and fiber photometry is detected. Chemogenetic tools selectively inhibited or activated vlPAG glutamatergic neurons. Cardiac function is assessed by echocardiography and histopathology, while inflammation is analyzed via Western blot and Reverse Transcription Quantitative Real-Time Polymerase Chain Reaction. Improvement of cardiac function: electroacupuncture significantly elevated cardiac function in MI mice to improve the prognostic level of mice; verification of neural mechanism: electroacupuncture selectively activated vlPAG glutamatergic neurons, and the cardioprotective effect of electroacupuncture is suppressed by inhibition of the vlPAG^Glu, whereas specific activation of this neuron can mimic the effect of electroacupuncture(EA). This study unveils a central “acupoint-brain-heart” axis, where EA at HT7 engages vlPAG to restore cardiac homeostasis. These findings bridge traditional acupuncture and modern neuroscience, proposing vlPAG glutamatergic pathways as novel targets for cardiovascular therapy.

This study explores the interaction between immune and cancer cells in the tumor microenvironment (TME) of cervical carcinoma (CC), with emphasis on tumor-associated macrophages (M2-TAMs) and the STAT3-NF-κB signaling pathway. It investigates how Treg cell polymorphisms and TAM infiltration through these pathways influence overall survival (OS) in CC patients. This prospective study follows 100 CC patients from 2018 to 2023 using qRT-PCR and immunohistochemistry on tumor samples, and flow cytometry on blood samples to evaluate immunosuppressive cytokines and Treg cell polymorphisms. High stromal CD163+204+ TAM density, mediated by STAT3/NF-κB, correlates with biomarkers such as Ki-67, VEGFα, and FOXP3 (p < 0.001). XPO5 expression is associated with increased STAT3, SNAIL, and HPV 16/18 levels. FOXP3 T allele deletion and HLA-G polymorphism in the blood of patients correlate with higher STAT3 tumor expression and elevated IL-4 and IL-17 blood cytokines. The CXCL12-CXCR4 axis shows a strong association with STAT3, SNAIL in TME and blood cytokines, including IL-6 and IL-12. Elevated CXCL12, CXCR4, and SNAIL expression in TME significantly increases mortality risk. These findings underscore the role of M2TAM infiltration and immune modulation in tumor progression and clinical outcomes in CC.

Acute Respiratory Distress Syndrome (ARDS) is a life-threatening condition characterized by severe inflammation and lung damage, leading to critical hypoxemia. Despite its high mortality rate, the only currently available treatment, Dexamethasone, is associated with significant side effects. This study aims to evaluate the efficacy of primed human umbilical cord blood-derived mesenchymal stem cells (hUCB-pMSCs) as a potential alternative treatment for ARDS. A novel lung microphysiological system (MPS) modeling the lung environment is developed and treated with lipopolysaccharide (LPS) to simulate ARDS. The effects of hUCB-pMSCs and dexamethasone are compared using state-of-the-art methods, including fluorescence-based imaging and single-cell RNA sequencing. The hUCB-pMSCs significantly activated angiogenesis-related pathways in endothelial cells and enhanced the formation of tip-like endothelial cells involved in new blood vessel formation. These findings are corroborated by fluorescence microscopy, demonstrating the robust potential of hUCB-pMSCs as a therapeutic approach. Overall, the results support the potential of hUCB-pMSCs as a promising alternative treatment for ARDS.

Biologic medicines (or biologics) have revolutionized the treatment of cancer, autoimmune disorders, and genetic conditions. Their therapeutic success stems from complex structural properties that confer high target specificity and biological compatibility. However, their high cost and complex manufacturing limit patient access, with annual treatment expenses often reaching tens of thousands of dollars per patient. Biosimilars, developed to match reference biologics in quality, safety, and efficacy, provide a pathway to curb escalating costs. Having generated more than 36 billion USD in healthcare savings over the past decade, their wider adoption remains challenged by stringent regulatory pathways and the market exclusivity of reference products. These limitations have spurred the development of biobetters, which are engineered biologics with enhanced stability, potency, half-life, or reduced immunogenicity that maximize patient benefit. This review explores the distinctions, development strategies, and regulatory challenges of biologics, biosimilars, and biobetters. Biosimilarity establishment and biobetter design strategies are examined with emphasis on enzyme-based examples such as L-asparaginase and glucarpidase. Advanced delivery technologies have also been demonstrated to improve drug stability, bioavailability, and patient adherence. Finally, emerging innovations and future directions underscore the transformative potential of these biopharmaceuticals in addressing unmet medical needs and expanding global access.

Diminished ovarian reserve (DOR), marked by reduced oocyte quantity and quality, remains therapeutically challenging. This study evaluates the protective effects of Qingxin Jianpi Decoction (QXJP) against cyclophosphamide (CTX)-induced DOR via integrated network pharmacology and experimental validation. Bioactive compounds in QXJP are screened (TCMSP: OB ≥30%, DL ≥0.18) and targets predicted (SwissTargetPrediction). Functional enrichment analysis is performed using DAVID. CTX-induced DOR rats receive QXJP (low/medium/high doses) or resveratrol. Ovarian histology, hormone levels (FSH, LH, E2, and AMH), apoptosis (Bax/Bcl-2, cleaved Caspase-3), ferroptosis markers (SLC7A11, ACSL4, MDA, and 4-HNE), and PI3K/AKT/Nrf2 pathway activity are quantified by Western blot or ELISA. Network pharmacology identifies 176 bioactive compounds targeting 297 DOR-associated genes, highlighting the PI3K-AKT pathway. QXJP restores estrous cyclicity, increases follicle counts, reduces fibrosis, and rebalances FSH, LH, E2, and AMH levels (all p < 0.01). It suppresses granulosa cell apoptosis (decreased Bax/Cleaved Caspase-3, increased Bcl-2), attenuated ferroptosis-related alterations (upregulated SLC7A11, downregulated MDA, 4-HNE, and ACSL4), and activates PI3K/AKT/Nrf2 signaling (increased p-PI3K/PI3K, p-AKT/AKT ratios; upregulates Nrf2, HO-1, and GPX4, p < 0.05). QXJP ameliorates CTX-induced DOR by attenuating ovarian apoptosis and ferroptosis via the PI3K/AKT/Nrf2 pathway. This multi-target mechanism underscores its potential as a herbal therapy for DOR.

The Hmox1 enzyme, which is the inducible enzyme among the Hmoxs, catalyzes the first and rate-limiting step in the heme degradation pathway, generating three byproducts, namely, carbon monoxide, free iron, and biliverdin. These byproducts can affect an array of biological processes; hence, Hmox1 modulates multiple metabolic processes. Along with the degradation of cytotoxic heme, Hmox1 provides protection against inflammation, apoptosis, and oxidative stress. It also ameliorates tissue injury, maintains iron homeostasis, and supports embryonic survival. Initially, different studies labeled it as an active cancer-assisting agent; however, multiple recent studies have shown that it also deters cancer progression. Hence, this review first looks into the traditional role of Hmox1 and various Hmox1 inducers. Second, there are multiple links between Hmox1 and different types of cancer, including how it acts as a promoter or plays an antitumor role in different or even the same cancers. On the basis of the available data, the work proposes a few speculations to explain this dual role of Hmox1 in cancer.

Bone metastasis causes severe complications for patients suffering from advanced-stage prostate cancer. Exercise is recommended to help maintain musculoskeletal health during treatment. As primary mechanosensors and regulators of bone homeostasis, osteocytes recently investigate for their roles in prostate cancer bone metastasis. Recently, in vivo studies show that exercise mitigates prostate tumor progression and preserves bone structure. In contrast, in vitro studies indicate direct prostate cancer–osteocyte interactions under mechanical loading conditions promote prostate cancer growth and migration but exclude other host cells present in the metastatic bone microenvironment. Thus, these in vitro findings are not consistent with recent in vivo results. In this study, the role of mechanically stimulated osteocytes during the initial stages of metastatis in osteoblast-rich areas is examined. When treated with conditioned media from flow-stimulated osteocytes, osteoblasts reduce PC-3 wound healing migration and invasion compared to static controls. Of interest, osteoblasts treated with flow-stimulated MLO-Y4 and primary osteocyte conditioned media suppress PC-3 cancer cell growth, alter cancer cell morphology, and preserve mineralized matrix in a microfluidic co-culture assay. Overall, the inhibitory role of mechanical loading of osteocytes on the early-stage metastasis of the endosteal surface during prostate cancer bone metastasis is demonstrated.

The 3D organization of the genome constitutes a spatial layer of information processing that helps govern gene expression and thus cell function. Advances in chromosome conformation capture sequencing have enabled detailed assessment of chromatin architecture, from enhancer–promoter loops to topological domains and higher-order contacts, across cell types and developmental states. While the ability to investigate genome conformation is maturing, the field faces a central challenge: The link between chromatin interactions and cellular function remains largely correlative, leaving their causality unresolved. This review explores how recent developments in genome engineering enable the targeted manipulation of 3D chromatin architecture – specifically DNA loops – to illuminate causal links between genome structure and function. Synthetic strategies are introduced that rewire enhancer–promoter communication through engineered chromatin loops, leveraging programmable DNA-binding platforms such as zinc fingers, transcription activator-like effectors (TALEs), and CRISPR-Cas9. The current limitations of these approaches related to efficiency, scalability, and specificity are also highlighted, and the strategies to address them are outlined. As these systems mature, programmable 3D genome engineering is emerging as a transformative pillar of synthetic biology, complementing sequence-based editing as a core modality for both understanding and ultimately reprogramming genome function.

This study investigates the effects of ion release and pH elevation from a biodegradable metallic magnesium (Mg) –30 calcium (Ca) coating on osteogenesis using osteoblast-like cells. The coating, formed on titanium (Ti) via magnetron sputtering, has previously been shown to enhance osteogenesis by promoting calcite formation on the Ti surface upon degradation in vitro study. However, the individual and combined roles of released Mg²⁺, Ca²⁺, and pH elevation remain unclear. To clarify these effects, culture media supplemented with Mg²⁺ and Ca²⁺ salts are prepared. Mg²⁺ at 4–5 mm promotes early alkaline phosphatase (ALP) activity compared to the 0.9 mm control, without affecting proliferation but suppressing mineralization. Ca²⁺ at 2.3–3 mm enhances ALP activity without affecting proliferation or mineralization compared to the 1.3–2.2 mm control. When both ions coexist, proliferation, ALP activity, and mineralization are enhanced compared to Mg²⁺ alone, suggesting a synergistic effect. Furthermore, the elevated pH resulting from the Mg–30Ca extract more effectively promotes proliferation, accelerates the peak of ALP activity, and supports mineralization than ions co-supplementation. These findings indicate that Mg–30Ca coatings enhance osteogenesis through both ion release and pH elevation, providing new insight into the osteogenic potential of biodegradable metallic coatings.

Metabolic dysfunction-associated steatotic liver disease (MASLD) and its progressive form metabolic dysfunction-associated steatohepatitis (MASH) are prevalent chronic liver diseases that are closely linked to metabolic syndrome, type 2 diabetes, and cardiovascular complications. Despite their rising incidence and growing socioeconomic burden, effective therapies remain limited. Traditional preclinical models often fail to replicate the complexity of human MASLD, particularly in capturing the interplay between patient-specific predisposition, metabolic dysfunction, immune activation and progressive fibrosis. In this review, a comprehensive overview of emerging human-based in vitro and ex vivo platforms is provided for use in MASLD research, including conventional 2D cultures, organoids, 3D spheroids, precision-cut liver slices, microphysiological systems, and bioprinted constructs. Their utility is evaluated for modeling different stages of MASLD and MASH and their alignment with key disease hallmarks is discussed. Furthermore, the different models are assessed for their capability to model pathophysiologically relevant nutritional exposure, to emulate genetic risk factors, to reflect the complex hepatic cell repertoire and to conduct high-throughput drug screenings. Recent successful applications of MASLD and MASH models are highlighted in drug discovery and development. Together, these insights aim to guide the refinement of human MASLD models to narrow the translational gap in MASH drug development.