This review aims to comparatively examine the structural differences, receptor interactions, downstream signaling effects, and pathophysiological roles of the two main isoforms of the VEGFA gene, VEGF165a and VEGF165b, which arise from alternative splicing of exon 8. Recent experimental and clinical studies conducted between 2020 and 2025 in both human and animal models were systematically reviewed to evaluate the biological functions, receptor-binding properties, and pro- and anti-angiogenic effects of VEGF165b. VEGF165a promotes endothelial cell proliferation, migration, and vascular permeability by activating VEGFR-2 through PI3K/Akt and MAPK/ERK pathways. In contrast, VEGF165b binds to the same receptors but induces weak signaling and competitively inhibits the effects of VEGF165a. While VEGF165b is predominantly expressed in healthy tissues, a shift in favor of VEGF165a is observed in pathological conditions such as cancer, proliferative diabetic retinopathy, and age-related macular degeneration. Conversely, excessive VEGF165b expression is associated with impaired angiogenesis in diseases such as peripheral artery disease, systemic sclerosis, and preeclampsia. Disruption in the VEGF165 isoform balance underlies many diseases characterized by either excessive or insufficient angiogenesis. In this context, isoform-specific therapeutic strategies—such as the modulation of alternative exon usage via splice-switching oligonucleotides—may allow the development of more precise and targeted vascular therapies in the future. The VEGF165a/VEGF165b ratio also holds promise as a biomarker for guiding personalized angiogenesis-modulating treatments.

The aim of this study was to investigate the impact of type 1 diabetes on lung tissue using histopathological and immunohistochemical techniques, with a particular focus on whether it induces endoplasmic reticulum stress in the lung. The experiment utilized 18 male Balb/c mice, two months old with an average weight of 40 grams, randomly assigned to three groups: Control (n = 6), Sham (n = 6), and Streptozotocin diabetes group (n= 6). Diabetes was induced in the Streptozotocin group via a single intraperitoneal injection of 100 mg·kg-1 Streptozotocin. Following the experimental period, histopathological, immunohistochemical, and semi-quantitative analyses were conducted. Histopathological analysis revealed significant degeneration, apoptotic changes in epithelial cells and connective tissue, capillary dilation and inflammatory cell infiltration in the Streptozotocin group compared with the control and sham groups. Immunohistochemical analyses revealed a strong positive immunoreactivity for glucose regulated protein 78, nuclear factor kappa B and caspase–3 in type I and II pneumocytes, club cells, endothelial cells and alveolar macrophages in the Streptozotocin group. These observations imply the possible induction of endoplasmic reticulum stress in the lungs by type 1 diabetes and finally culminate into various histopathological alterations.

Diabetes mellitus (DM) causes oxidative stress, neuroinflammation, and endoplasmic reticulum (ER) dysfunction that contribute to neurodegeneration. This study investigated the effects of 18β-glycyrrhetinic acid-loaded silver nanoparticles (18β-GA-AgNPs) on brain injury in diabetic rats. Fifty-six male Wistar rats were divided into eight groups: Sham, 18β-GA, AgNPs, 18β-GA-AgNPs, DM, DM+18β-GA, DM+AgNPs, and DM+18β-GA-AgNPs. Diabetes was induced by alloxan (120 mg/kg, IP), and treatments were administered orally for 14 days. Biochemical markers (MDA, GSH, SOD), histopathology, and expression of ER stress and apoptotic proteins (ATF6, IRE1, Caspase-3, BCL-2, CREB, TNF-α, and IL-1β) were evaluated. The DM group exhibited significant increases in MDA, TNF-α, IL-1β, ATF6, and Caspase-3 with reduced GSH, SOD, and BCL-2, indicating oxidative stress, inflammation, apoptosis, and ER stress. In contrast, IRE1 levels remained unchanged in DM rats but showed a slight elevation in the AgNPs group. Treatment with 18β-GA-AgNPs markedly reduced MDA, TNF-α, IL-1β, ATF6, and Caspase-3, while restoring GSH, SOD, BCL-2, and CREB expression. Histopathological analysis confirmed neuronal apoptosis and perivascular and extracellular space enlargement in DM rats, whereas 18β-GA-AgNPs substantially attenuated these changes. Overall, 18β-GA-AgNPs provided synergistic neuroprotection by suppressing oxidative stress, inflammation, and ER stress while enhancing antioxidant and anti-apoptotic defenses. These findings suggest that 18β-GA-AgNPs may represent a promising therapeutic strategy against diabetes-associated neurodegeneration, although further long-term, ultrastructural, and sex-inclusive studies are warranted.

Diabetic foot ulcers (DFUs) remain among the most disabling and costly complications of type 2 diabetes mellitus, driving the majority of non-traumatic lower-limb amputations and carrying a five-year mortality that rivals many aggressive cancers. Their refractory nature reflects a self-perpetuating pathological microenvironment in which hyperglycaemia, oxidative stress, advanced glycation end-product accumulation, immune senescence, sustained pro-inflammatory macrophage activation, impaired angiogenesis, and biofilm-forming, frequently drug-resistant infections converge to arrest the normal progression of wound repair. Conventional standard-of-care dressings and off-loading strategies address symptoms rather than these interlocking mechanisms and leave a large therapeutic gap. This chapter synthesises the most recent advances across three rapidly maturing and increasingly convergent domains of translational wound medicine: smart biomaterials, in particular stimuli-responsive, self-healing, conductive and sensing hydrogels engineered to actively remodel the wound micro-environment; nano-medicine, spanning metallic nanoparticles, metal-organic frameworks, catalytic nanozymes, electrospun nano-fibres, and phototherapeutic nano-platforms that deliver multi-modal anti-microbial and pro-regenerative activity; and regenerative medicine, encompassing mesenchymal stem cells, engineered exosomes, bio-engineered skin substitutes and three-dimensional bioprinting. Emphasis is placed on integrated next-generation platforms, including exosome-laden responsive hydrogels, glucose-oxidase-enabled photothermal micro-needles and closed-loop theranostic wearables that couple continuous biosensing with on-demand therapy. The mechanistic rationale linking each technology to a specific pathophysiological target is highlighted, and the principal barriers to clinical translation, including vascularisation, scalable manufacturing, standardisation, safety and reimbursement, are critically appraised. Together, these developments signal a paradigm shift from passive wound coverage towards precision, micro-environment-adaptive and personalised DFU therapeutics.

İnsan yaşamı, ilk hücresel farklılaşmalardan başlayarak karmaşık fizyolojik süreçler, çevresel etkiler, sağlık davranışları ve yaşamın son dönemlerine uzanan bütüncül bir yolculuktur. Bu yolculuğun anlaşılması, yalnızca tek bir disiplinin değil, sağlık bilimlerinin farklı alanlarının ortak bakış açısını gerektirir. DOĞUM-YAŞAM-ÖLÜM: Çok Disiplinli Sağlık Bilimleri Araştırmaları, embriyolojik gelişimden stres fizyolojisine, bağımlılık tedavilerinden dijital sağlık uygulamalarına, yaşam sonu bakımından ölümün klinik, etik ve hukuki boyutlarına kadar uzanan güncel ve özgün konuları bir araya getirmektedir. Bu eser, sağlık bilimleri alanındaki araştırmacılar, akademisyenler, öğrenciler ve sağlık profesyonelleri için disiplinler arası bir başvuru kaynağı olmayı amaçlamaktadır. Yaşamın başlangıcını, sürdürülebilirliğini ve sonlanışını bilimsel bir bakış açısıyla ele alan kitap, okuyucuyu sağlık olgusuna daha geniş bir perspektiften bakmaya davet etmektedir.