Advanced biology最新文献

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.

Anaesthetics temporarily inhibit neural activity by acting on voltage-gated sodium channels and GABA receptors. Although their neurological mechanisms are well-defined, their wider cellular effects, especially in non-neuronal systems, are inadequately understood. This study utilized Solanum lycopersicum plant's root apex cells as a transparent model to examine anaesthetic-induced subcellular alterations via live-cell fluorescence imaging, immunostaining, and super-resolution microscopy. These findings demonstrate the hierarchical cascade of organelle dysfunction, such as mitochondria, lysosomes, vesicle trafficking, and nuclear architectures under anaesthesia in plants. The nucleus is identified as the main controller of recovery potential and cellular fate. In a time dependent experiment, it is found that plant cells exposed to lidocaine for up to 4 h can still recover mitochondrial potential, lysosomal function, and nuclear integrity when anaesthesia is removed. However, beyond 4 h the damage, especially to the nucleus, is irreversible, and cells proceeded to cell death. The data further demonstrate that organelles can recover after brief exposure, but prolonged exposure stops recovery, resulting in the irreversible degradation of the nucleus leading to complete cell death. The results may help to uncover organelle-related dysfunction under anaesthetic toxicity and provide a clearer understanding for minimizing or reversing such damage.

Nasopharyngeal carcinoma (NPC), an Epstein-Barr virus (EBV)-driven malignancy with geographic prevalence in Asia, faces therapeutic challenges due to acquired resistance. Ferroptosis—an iron-dependent cell death pathway driven by lipid peroxidation—emerges as a critical regulator of NPC pathobiology. This review synthesizes how ferroptosis suppression promotes NPC tumor growth, metastasis, and therapy resistance. Key mechanisms include: 1. EBV-mediated activation of p62-Keap1-NRF2/GPX4 and GPX4-TAK1 axes conferring chemo/radioresistance; 2. Extracellular vesicle (EV)-mediated transfer of ITGB3 or SCARB1 reprogramming tumor-associated macrophages (TAMs) and inhibiting ferroptosis in circulating cells; 3. Metabolic rewiring (e.g., CAPRIN2/HMGCR, P4HA1/HMGCS1) enhancing metastasis. Additionally, ferroptosis induction via radiotherapy, natural compounds (solasodine, luteolin), repurposed drugs (disulfiram/copper), or nanotechnology synergizes with immunotherapy by promoting lipid peroxidation and reversing EBV-mediated immune evasion. Targeting ferroptosis regulators (SLC7A11, GPX4, FTO, CD38) overcomes resistance, positioning ferroptosis modulation as a transformative strategy for NPC management.

Type 1 Diabetes (T1D) is characterized by autoimmune destruction of pancreatic beta cells, resulting in insulin deficiency. Natural-based biomaterials like collagen offer promising avenues mimicking tissue microenvironments. However, limited research has been conducted on crosslinked collagen microgels with vascular endothelial growth factor (VEGF) and their effects on biomaterial stability and beta cell function. The aim is to synthesize functionalized-VEGF collagen microgels that mimic the pancreatic environment to sustain pancreatic beta cells for diabetes therapy. Physicochemical analysis confirms the incorporation of functional groups and structural stability over time. Mechanical testing shows adequate resistance to deformation. Metabolic activity increases after 48 h of incubation for the 1 and 3 ng mL⁻¹ VEGF concentrations, as demonstrated by enzymatic and microscopic assays. DNA quantification confirms enhanced cell proliferation at 72 h across all VEGF concentrations. Further analysis shows that VEGF microgels can maintain oxygen consumption and insulin secretion under glucose stimulation of pancreatic beta cells. These findings highlight the intrinsic advantages of collagen-based platforms for cell support and suggest their potential for translational applications. Future studies will focus on molecular-level interactions and in vivo validation, placing this strategy as a promising candidate for advanced diabetes therapy.