Growth Factor Synthesis Research Articles

Tumor-induced phosphopenic osteomalacia: modern approaches to diagnostics and treatment

Phosphopenic osteomalacia (PPOM) is a rare variant of paraneoplastic syndrome caused by tumor synthesis of fibroblast growth factor 23 (FGF23). FGF23 secretion leads to a decrease in phosphate reabsorption and calcitriol levels, which leads to the development of severe hypophosphataemia and hypocalcaemia. FGF23 synthesis is predominantly associated with benign mesenchymal tumors, but has also been described in malignant neoplasms. The main clinical manifestations of PPOM are generalized myalgias and myopathy, ostealgia, pathological fractures, etc. The diagnosis of the disease requires a step-by-step investigation using somatostatin receptor-based imaging techniques, as these have the highest sensitivity for the detection of neoplasms causing osteomalacia. Surgical intervention is clearly the treatment of choice. Promising non-surgical methods include treatment with burosumab and somatostatin analogues.

Current ideas on the pathogenesis of osteoporosis in chronic lymphatic leukemia (literature review)

Background. Chronic lymphocytic leukemia (CLL) is the second most common hematological malignancy without a trend towards a decrease in its incidence. 66 % of patients with CLL experience bone fractures as a result of osteoporosis in all age groups, and the detection frequency is no more than 15 %. Insufficient understanding of the osteoporosis pathogenesis in CLL leads to problems in diagnosis, prevention and therapy.The aim of the study. To analyze modern data on the features of the osteoporosis pathogenesis in chronic lymphocytic leukemia.Results and discussion. Osteoporosis is formed when osteoresorption prevails over osteosynthesis due to intercellular interactions of bone tissue and the immune system, dysregulation of intracellular signaling pathways RANKL/RANK/OPG, Wnt, FoxO, RUNX2, initiated by cytokines, growth factors, prostaglandins, and hormones. The degree of osteoresorption in CLL is associated with the severity of the clinical course, chemotherapy and hormonal deprivation. The osteoporosis pathogenesis in CLL is considered as part of a complex set of events, including, firstly, the interaction between leukemic cells (overexpression of PTHrP, RANKL) and bone cells (synthesis of growth factors), which forms a vicious circle of osteoresorption and tumor growth. Secondly, pro-inflammatory markers in CLL (tumor necrosis factor α, interleukin (IL) 1β, IL-6, IL-8, IL-11, granulocyte-macrophage colony-stimulating factor, macrophage colony-stimulating factor, transforming growth factor β, prostaglandin E2) limit osteoblast-induced osteosynthesis and stimulate the expansion of osteoclasts from monocytic suppressor cells of myeloid origin with or without the participation of the RANKL/RANK system. Thirdly, oxidative stress in CLL and impaired efficiency of antioxidant protection with the participation of fibroblast growth factor 23, transcription factor Nrf-2 with activation of JNK, ERK1/2, NF-κB, and also an increase in the RANKL/OPG ratio lead to inhibition of osteoblastogenesis.Conclusion. Analyzing and systematizing data on the osteoporosis pathogenesis in CLL are instrumental for the development of diagnostic criteria for osteoporosis in chronic lymphocytic leukemia that are much-needed in clinical practice and for the improvement of therapeutic tactics.

Research Progress on the Mechanism of Chinese Herbal Compounds Treating Benign Prostatic Hyperplasia by Regulating Inflammatory Response

Benign prostatic hyperplasia (BPH) is one of the most common benign diseases in middle-aged and elderly men. Its main clinical manifestations are frequent urination, urgent urination, weak urine flow, other lower urinary tract symptoms, serious urinary retention, and urinary incontinence. Chinese herbal compounds are widely used in the clinical treatment of BPH with good efficacy and safety, reflecting the advantages of multi-target and multi-approach traditional Chinese medicine (TCM) treatment. There is usually a high level of inflammation in the affected area of BPH, and its persistence affects the whole body, causing multiple complications and accelerating the development of the disease. Inflammation can directly stimulate the proliferation of prostate cells and drive other pathological mechanisms to jointly promote the development of diseases, such as participating in oxidative stress, driving growth factor synthesis, destroying the imbalance between apoptosis and proliferation, and promoting fibrosis. To more fully elucidate the mechanism of action of Chinese herbal compounds in the treatment of BPH, this paper reviews the literature in recent years, beginning with basic research on the intervention of Chinese herbal compounds in BPH inflammation, to provide further ideas for relevant research on the prevention and treatment of BPH inflammation by TCM.

Physical stimulations and their osteogenesis-inducing mechanisms.

Physical stimulations such as magnetic, electric and mechanical stimulation could enhance cell activity and promote bone formation in bone repair process via activating signal pathways, modulating ion channels, regulating bonerelated gene expressions, etc. In this paper, bioeffects of physical stimulations on cell activity, tissue growth and bone healing were systematically summarized, which especially focused on their osteogenesis-inducing mechanisms. Detailedly, magnetic stimulation could produce Hall effect which improved the permeability of cell membrane and promoted the migration of ions, especially accelerating the extracellular calcium ions to pass through cell membrane. Electric stimulation could induce inverse piezoelectric effect which generated electric signals, accordingly up-regulating intracellular calcium levels and growth factor synthesis. And mechanical stimulation could produce mechanical signals which were converted into corresponding biochemical signals, thus activating various signaling pathways on cell membrane and inducing a series of gene expressions. Besides, bioeffects of physical stimulations combined with bone scaffolds which fabricated using 3D printing technology on bone cells were discussed. The equipments of physical stimulation system were described. The opportunities and challenges of physical stimulations were also presented from the perspective of bone repair.

Mechanism of action of montmorillonite powder on injury and repair factors in Stage II pressure ulcers in model mice.

This study aims to elucidate the therapeutic effects and underlying mechanisms of montmorillonite powder on wound healing in mice with Stage II pressure ulcers, thereby providing a robust foundation for its clinical application in the treatment of such ulcers. Sixty 8-week-old specific pathogen-free male BALB/c mice were randomly allocated into three groups: a model group (where Stage II pressure ulcers were induced using the magnet pressure method and the wounds were dressed with gauze soaked in 0.9% sodium chloride solution), a treatment group (where, following the induction of Stage II pressure ulcer models, wounds were uniformly treated with montmorillonite powder), and a control group (where magnets were placed in the same location without exerting magnetic pressure). Skin histopathology was assessed via light microscopy. Wound healing progress over various intervals was quantified utilizing Image-Pro Plus software. Histopathological alterations in the wounds were examined through hematoxylin and eosin (H&E) staining. The expression of growth factor proteins within the wound tissue was analyzed using the streptavidin-peroxidase method. Furthermore, the levels of vascular endothelial growth factor (VEGF), collagen types I and III (COL-I, COL-III) proteins were quantified via Western blotting, serum concentrations of inflammatory mediators in mice were determined by enzyme-linked immunosorbent assay, and the levels of oxidative stress markers in wound tissues were measured using UV-visible spectrophotometry. The treatment group exhibited significantly reduced serum levels of interleukin-1β, interleukin-6, and tumor necrosis factor-alpha, and elevated levels of interleukin-4 compared to the model group (p<0.05). Additionally, the expression of transforming growth factor-beta1, basic fibroblast growth factor, epidermal growth factor, VEGF, COL-I, and COL-III proteins in wound tissues was significantly higher in the treatment group than in the model group (p<0.05). Levels of superoxide dismutase and glutathione peroxidase in wound tissues were higher, and levels of malondialdehyde were lower in the treatment group compared to the model group (p<0.05). Montmorillonite powder facilitates wound healing and augments the healing rate of Stage II pressure ulcers in model mice. Its mechanism of action is likely associated with mitigating wound inflammation, reducing oxidative stress damage, promoting angiogenesis, and enhancing the synthesis of growth factors and collagen.

Vitamin D in Central Nervous System: Implications for Neurological Disorders.

Vitamin D, obtained from diet or synthesized internally as cholecalciferol and ergocalciferol, influences bodily functions through its most active metabolite and the vitamin D receptor. Recent research has uncovered multiple roles for vitamin D in the central nervous system, impacting neural development and maturation, regulating the dopaminergic system, and controlling the synthesis of neural growth factors. This review thoroughly examines these connections and investigates the consequences of vitamin D deficiency in neurological disorders, particularly neurodegenerative diseases. The potential benefits of vitamin D supplementation in alleviating symptoms of these diseases are evaluated alongside a discussion of the controversial findings from previous intervention studies. The importance of interpreting these results cautiously is emphasised. Furthermore, the article proposes that additional randomised and well-designed trials are essential for gaining a deeper understanding of the potential therapeutic advantages of vitamin D supplementation for neurological disorders. Ultimately, this review highlights the critical role of vitamin D in neurological well-being and highlights the need for further research to enhance our understanding of its function in the brain.

Altered hypoxia-induced cellular responses and inflammatory profile in lung fibroblasts from COPD patients compared to control subjects

BackgroundChronic obstructive pulmonary disease (COPD) is a heterogeneous disease characterized by chronic bronchitis, emphysema and vascular remodelling. The disease is associated with hypoxia, inflammation and oxidative stress. Lung fibroblasts are important cells in remodelling processes in COPD, as main producers of extracellular matrix proteins but also in synthesis of growth factors and inflammatory mediators.MethodsIn this study we aimed to investigate if there are differences in how primary distal lung fibroblasts obtained from COPD patients and healthy subjects respond to hypoxia (1% O2) and pro-fibrotic stimuli with TGF-β1 (10 ng/mL). Genes and proteins associated with oxidative stress, endoplasmic reticulum stress, remodelling and inflammation were analysed with RT-qPCR and ELISA.ResultsHypoxia induced differences in expression of genes involved in oxidative stress (SOD3 and HIF-1α), ER stress (IRE1, PARK and ATF6), apoptosis (c-Jun and Bcl2) and remodelling (5HTR2B, Collagen7 and VEGFR2) in lung fibroblasts from COPD subjects compared to control subjects, where COPD fibroblasts were in general less responsive. The release of VEGF-C was increased after hypoxia, whereas TGF-β significantly reduced the VEGF response to hypoxia and the release of HGF. COPD fibroblasts had a higher release of IL-6, IL-8, MCP-1 and PGE2 compared to lung fibroblasts from control subjects. The release of inflammatory mediators was less affected by hypoxia, whereas TGFβ1 induced differences in inflammatory profile between fibroblasts from COPD and control subjects.ConclusionThese results suggest that there is an alteration of gene regulation of various stress responses and remodelling associated mediator release that is related to COPD and hypoxia, where fibroblasts from COPD patients have a deficient response.

Intensity of subarachnoid space inflammation corresponds to the evolution of vessel wall remodeling during the acute and chronic phases of bacterial meningitis

AbstractCerebrovascular alterations in acute bacterial meningitis significantly contribute to adverse patient outcomes, with reported complication rates ranging from 10% to 29%. Focal alterations in arterial lumens, leading to vasoconstriction, are common in cerebral ischemic and inflammatory conditions, such as bacterial meningitis, presenting neurological complications, such as seizures, brain swelling, hydrocephalus, hearing loss and ischemic or hemorrhagic brain damage. The observed arterial narrowing during meningitis is attributed to diverse factors, including direct encroachment by inflammatory exudate, vascular wall edema, vasospasm, and vasculitis due to cellular infiltration and vessel remodeling. Early‐stage constriction might result from a watery exudate's encroachment, whereas persistent inflammation leads to thicker exudates, attracting inflammatory cells and inducing arteriopathic growth factor synthesis. This process promotes structural modifications in the vessel wall, progressing from subintimal infiltration to organic intimal thickening, culminating in vasculitis and the risk of cerebral ischemia. Accordingly, this review seeks to more clearly delineate the intricate relationship between subarachnoid space inflammation and acute and chronic vessel wall remodeling during bacterial meningitis. Conceivably, understanding this pathological process holds promise in unveiling potential treatment avenues to improve patient outcomes, and reduced morbidity and mortality associated with cerebrovascular complications during bacterial meningitis.

Naringenin as potent anticancer phytocompound in breast carcinoma: from mechanistic approach to nanoformulations based therapeutics.

The bioactive compounds present in citrus fruits are gaining broader acceptance in oncology. Numerous studies have deciphered naringenin's antioxidant and anticancer potential in human and animal studies. Naringenin (NGE) potentially suppresses cancer progression, thereby improving the health of cancer patients. The pleiotropic anticancer properties of naringenin include inhibition of the synthesis of growth factors and cytokines, inhibition of the cell cycle, and modification of several cellular signaling pathways. As an herbal remedy, naringenin has significant pharmacological properties, such as anti-inflammatory, antioxidant, neuroprotective, hepatoprotective, and anti-cancer activities. The inactivation of carcinogens following treatment with pure naringenin, naringenin-loaded nanoparticles, and naringenin combined with anti-cancer agents was demonstrated by data in vitro and in vivo studies. These studies included colon cancer, lung neoplasms, breast cancer, leukemia and lymphoma, pancreatic cancer, prostate tumors, oral squamous cell carcinoma, liver cancer, brain tumors, skin cancer, cervical and ovarian cancers, bladder neoplasms, gastric cancer, and osteosarcoma. The effects of naringenin on processes related to inflammation, apoptosis, proliferation, angiogenesis, metastasis, and invasion in breast cancer are covered in this narrative review, along with its potential to develop novel and secure anticancer medications.

(091) EXPOSURE OF THE VESTIBULE TO A POSSIBLE ALLERGIC TRIGGER AT A VERY YOUNG AGE: LIFELONG NEUROPROLIFERATIVE VESTIBULODYNIA

Abstract Introduction Vestibular fibroblasts from patients with neuroproliferative vestibulodynia (NPV) versus age-matched controls produced higher proinflammatory cytokine levels of various interleukins when provoked with candida albicans in vitro. In genetically susceptible patients, this enhanced cytokine synthesis is hypothesized, in part, to lead to neuroproliferation in vestibular tissue resulting in allodynia/hyperalgesia. Patients with acquired NPV, who initially experienced pain-free penetration in their early adult reproductive life, may experience persistent severe vestibular burning following an allergic reaction to a topical agent applied to the non-keratinized vestibular epithelium. In contrast, patients with lifelong NPV present with the classic history of inability to insert a tampon at menarche (mean age 12.4 years). Patients with lifelong NPV may have unknowingly been exposed to an allergen early in their childhood, potentially even triggered from ointments used in infancy to protect from diaper rash, resulting in local vestibular mast cell accumulation in genetically susceptible patients. Agents commonly used to prevent are zinc oxide 40%, (Desitin) with inactive ingredients petrolatum, cod liver oil, lanolin, talc, glycerin, sorbitan sesquioleate, beeswax, tocopheryl acetate and fragrance and A+D ointment that includes petroleum jelly, lanolin, lavender oil, light liquid paraffin, vitamin A and vitamin D. It is possible an allergic reaction could result from any of these ingredients when applied to the non-keratinized vestibular epithelium. Objective We wished to better understand the possible triggering event in patients with lifelong NPV. Methods A chart review was performed of patients who presented between January 2019 and June 2023 who were clinically suspected to have lifelong NPV based on a history of inability to use tampons and inability to have pain-free penetration and histopathlogically confirmed to have NPV. Information was obtained from a parent or caregiver who regularly changed patient’s diapers as to what agents were utilized to manage diaper rash. Results Our patient cohort included 14 individuals with vulvas, mean age 25 (range 18-37) years. One patient prone to diaper rash was treated with A+D baby diaper rash ointment and Flanders buttocks ointment (zinc oxide, white petrolatum, white beeswax, Peruvian balsam). One patient had a “bad” yeast infection as a baby and received “topical antibiotics”. Five patients claimed Desitin and Vaseline were used while six patients claimed Desitin alone, two of whom cryied every time they Desitin was applied. One patient from Puerto Rico, received “a sock filled with cornstarch that dabbed the vaginal area and crevices after wiping the area clean”. Conclusions The endodermal vestibular epithelium is not protected by a keratin layer, including in babies at a very young age. In genetically susceptible babies, an allergic reaction to an active/inactive agent used to prevent or treat diaper rash could have potentially triggered mast cell accumulation in the baby’s vestibule leading to increased synthesis of cytokines and growth factors resulting in neuroproliferation consistent with lifelong NPV, evidenced by the inability to place a tampon at menarche. More research into this concern is needed. Disclosure No.

Molecular Mechanisms in Tumorigenesis of Hepatocellular Carcinoma and in Target Treatments-An Overview.

Hepatocellular carcinoma is the most common primary malignancy of the liver, with hepatocellular differentiation. It is ranked sixth among the most common cancers worldwide and is the third leading cause of cancer-related deaths. The most important etiological factors discussed here are viral infection (HBV, HCV), exposure to aflatoxin B1, metabolic syndrome, and obesity (as an independent factor). Directly or indirectly, they induce chromosomal aberrations, mutations, and epigenetic changes in specific genes involved in intracellular signaling pathways, responsible for synthesis of growth factors, cell proliferation, differentiation, survival, the metastasis process (including the epithelial-mesenchymal transition and the expression of adhesion molecules), and angiogenesis. All these disrupted molecular mechanisms contribute to hepatocarcinogenesis. Furthermore, equally important is the interaction between tumor cells and the components of the tumor microenvironment: inflammatory cells and macrophages-predominantly with a pro-tumoral role-hepatic stellate cells, tumor-associated fibroblasts, cancer stem cells, extracellular vesicles, and the extracellular matrix. In this paper, we reviewed the molecular biology of hepatocellular carcinoma and the intricate mechanisms involved in hepatocarcinogenesis, and we highlighted how certain signaling pathways can be pharmacologically influenced at various levels with specific molecules. Additionally, we mentioned several examples of recent clinical trials and briefly described the current treatment protocol according to the NCCN guidelines.

VEGF-R2/CAV-1 Interaction Induced by Resveratrol/Eicosapentaenoic Acid/Docosahexaenoic Acid-Enriched Formulation through Functional Detergent-Resistant Membranes Is Associated with Decreased VEGF-A Release in ARPE-19 Cells.

Omega-3 fatty acids (O3FAs) and resveratrol (RSV) are known to be beneficial for certain eye diseases, such as age-related macular degeneration (AMD). Neovascular AMD is characterized by abnormal blood vessel formation due to the excessive synthesis of vascular endothelial growth factor (VEGF) by retinal pigment epithelium (RPE) cells. The study investigates whether a formulation based on eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and RSV is capable of counteracting VEGF-A secretion, and elucidates the molecular mechanism. The study finds, using ELISA, that O3FAs/RSV reduces VEGF-A secretion in human RPE cells. This phenomenon is related to the increased interaction between VEGF-receptor 2 (VEGF-R2) and caveolin-1 (CAV-1), a protein of detergent-resistant membranes (DRMs), as determined by co-immunoprecipitation and proximity ligation assay. Using microscale thermophoresis, the study confirms that O3FAs/RSV causes a high-affinity interaction. Isolation and analysis of DRMs reveal that this interaction is concomitant with VEGF-R2 relocalization in DRMs. The depletion of DRMs by a cholesterol-chelating agent blocks the VEGF-R2/CAV-1 interaction and EPA/DHA/RSV-mediated impairment of VEGF production. This specific interaction can provide a new strategy for countering VEGF-A production in human RPE cells and, consequently, reducing neovascularization in AMD. Further preclinical studies involving O3FAs and polyphenols are warranted.

Involvement of somatotrophic hormones in the postpartum regulation of ovarian activity in mares

Mares resume ovarian activity rapidly after foaling. Besides follicle-stimulating hormone (FSH) and luteinizing hormone (LH), the pituitary synthesizes prolactin and growth hormone which stimulate insulin-like growth factor (IGF) synthesis in the liver. We tested the hypothesis that follicular growth is initiated already antepartum, mares with early and delayed ovulation differ in IGF-1 release and that there is an additional IGF-1 synthesis in the placenta. Plasma concentrations of LH, FSH, IGF-1, IGF-2, activin and prolactin. IGF-1, IGF-2, prolactin and their receptors in placental tissues were analyzed at the mRNA and protein level. Follicular growth was determined from 15 days before to 15 days after foaling in 14 pregnancies. Mares ovulating within 15 days postpartum formed group OV (n=5) and mares not ovulating within 15 days group NOV (n=9). Before foaling, follicles with a diameter >1 cm were present in all mares and their number increased over time (p<0.05). Follicle growth after foaling was more pronounced in OV mares (day p<0.001, group p<0.05, day x group p<0.05) in parallel to an increase in LH concentration (p<0.001, day x group p<0.001) while FSH increased (p<0.001) similarly in both groups. Plasma concentrations of IGF-1 and prolactin peaked one day after foaling (p<0.001). The IGF-1 mRNA abundance was higher in the allantochorion but lower in the amnion of OV versus NOV mares (group p=0.01, localization x group p<0.01). The IGF-1 receptor mRNA was most abundant in the allantochorion (p<0.001) and IGF-1 protein was expressed in placental tissue without differences between groups. In conclusion, follicular growth in mares is initiated before foaling and placental IGF-1 may enhance resumption of ovulatory cycles.

Phosphate sensing in health and disease.

Disruptions of phosphate homeostasis are associated with a multitude of diseases with insufficient treatments. Our knowledge regarding the mechanisms underlying metazoan phosphate homeostasis and sensing is limited. Here, we highlight four major advancements in this field during the last 12-18 months. First, kidney glycolysis senses filtered phosphate, which results in the release of glycerol 3-phosphate (G-3-P). Circulating G-3-P then stimulates synthesis of the phosphaturic hormone fibroblast growth factor 23 in bone. Second, the liver serves as a postprandial phosphate reservoir to limit serum phosphate excursions. It senses phosphate ingestion and triggers renal excretion of excess phosphate through a nerve-dependent mechanism. Third, phosphate-starvation in cells massively induces the phosphate transporters SLC20A1/PiT1 and SLC20A2/PiT2, implying direct involvement of cellular phosphate sensing. Under basal phosphate-replete conditions, PiT1 is produced but immediately destroyed, which suggests a novel mechanism for the regulation of PiT1 abundance. Fourth, Drosophila melanogaster intestinal cells contain novel organelles called PXo bodies that limit intracellular phosphate excursions. Phosphate starvation leads to PXo body dissolution, which triggers midgut proliferation. These studies have opened novel avenues to dissect the mechanisms that govern metazoan phosphate sensing and homeostasis with the potential to identify urgently needed therapeutic targets.

Low-Dose Naltrexone as an Adjuvant in Combined Anticancer Therapy.

Naltrexone (NTX) is a non-selective antagonist of opioid receptors, primarily used in the therapy of opioid and alcohol dependence. Low-dose naltrexone (LDN) exhibits antagonistic action against the opioid growth factor receptor (OGFr), whose signaling is associated with the survival, proliferation, and invasion of cancer cells. The mechanism of action of LDN depends on the dose and duration of the OGFr blockade, leading to a compensatory increase in the synthesis of the opioid growth factor (OGF), which has an inhibitory effect on carcinogenesis. Numerous studies on in vitro and in vivo models provide evidence of LDN's positive impact on inhibiting the OGF-OGFr axis in cancers. LDN's unique mechanism of action on cancer cells, lack of direct cytotoxic effect, and immunomodulating action form the basis for its use as an adjuvant in chemotherapy and immunotherapy of cancerous lesions.

Effects of mitochondrial transplantation on chronic pressure wound healing in a human patient

Background aimsWound healing is a multistage process that requires a concerted effort of various cell types. The intricate processes involved in the healing of wounds result in high energy requirements. Furthermore, mitochondria play a crucial role in the healing process because of their involvement in neo angiogenesis, growth factor synthesis, and cell differentiation. It is unclear how mitochondria transplantation, a promising new approach, influences wound healing. MethodsIn this study, healthy autologous mitochondria obtained from skeletal muscle were injected into chronic pressure wounds as an intervention to promote wound healing. ResultsMitochondrial transplantation accelerated wound healing by reducing wound size, increasing granulation tissue, and hastening epithelialization. ConclusionsThis study is the first to demonstrate the therapeutic efficacy of mitochondrial transplantation in wound healing.

Tremendous Fidelity of Vitamin D3 in Age-related Neurological Disorders.

Vitamin D3 (VD) is a secosteroid hormone and shows a pleiotropic effect in brain-related disorders where it regulates redox imbalance, inflammation, apoptosis, energy production, and growth factor synthesis. Vitamin D3's active metabolic form, 1,25-dihydroxy Vitamin D3 (1,25(OH)2D3 or calcitriol), is a known regulator of several genes involved in neuroplasticity, neuroprotection, neurotropism, and neuroinflammation. Multiple studies suggest that VD deficiency can be proposed as a risk factor for the development of several age-related neurological disorders. The evidence for low serum levels of 25-hydroxy Vitamin D3 (25(OH)D3 or calcidiol), the major circulating form of VD, is associated with an increased risk of Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), dementia, and cognitive impairment. Despite decades of evidence on low VD association with neurological disorders, the precise molecular mechanism behind its beneficial effect remains controversial. Here, we will be delving into the neurobiological importance of VD and discuss its benefits in different neuropsychiatric disorders. The focus will be on AD, PD, and HD as they share some common clinical, pathological, and epidemiological features. The central focus will be on the different attributes of VD in the aspect of its anti-oxidative, anti-inflammatory, anti-apoptotic, anti-cholinesterase activity, and psychotropic effect in different neurodegenerative diseases.

Stability and Safety Analysis of Statin-Loaded Nano-films for the Treatment of Diabetic Wound

Diabetes mellitus (DM) is a metabolic disease that delays the regular stages of the wound's healing process due to delayed inflammatory stages. Due to foot pressure points, chronic foot wounds are ultimately considered the primary cause of lower leg amputation. Diabetic patients have vascular dysfunction and neuropathy, leading to inadequate oxygen supply to the wound area. Statins have a crucial role in the regulation of angiogenesis that could increase vascular endothelial growth factor (VEGF) synthesis. By offering a localized treatment approach while minimizing systemic side effects associated with oral medication, this study aimed to develop statin-loaded nanofilms to determine their stability and safety among healthy individuals as a potential procedure for diabetic wound healing. Simvastatin (SIM) loaded nanofilms formulations (F1-F10) were prepared using the solvent casting method. The formulation was optimized based on tests such as physical appearance, tensile strength, microscopic photographs, morphology, and drug content uniformity. ICH guidelines were followed to determine various parameters (physical appearances, tensile strength, microscopic photographs, morphology, and drug content uniformity) for six-month stability study at three different storage conditions. Safety analysis of the nanofilms was performed on healthy human skin using the Draize skin irritation test. Results showed F7 formulation was considered an optimized formulation as well as stable through the storage period at 4 ± 2°C, 25 ± 2°C, and 40 ± 2 °C. Furthermore, Primary Irritation Index results (PII was 0 showed no irritation in case and control groups) indicate its safety and biocompatibility to skin. Thus, the optimized statin-loaded nanofilm is stable, safe, and non-toxic, which may be used as a potential diabetic wound healing agent.

Effects of an Ultra-Polished Scalpel on Incisional Wounds in a Diabetic Model.

Inflammation after surgical incisions is related to the degree of tissue damage. Healing with low inflammation is desirable, especially in patients with compromised healing potential. This experimental study was conducted to assess the degree of inflammatory reaction and scar formation from incisions made by an ultra-polished scalpel (UPS). Two paravertebral incisions were made with a conventional scalpel (CS) and a UPS in 18 individual rats with diabetes. The fibrotic tissue (scar) area and expression levels of collagen, transforming growth factor, and matrix metalloproteinases were quantified on postoperative days 3, 7, and 30. The scar widths and areas were significantly lower in the UPS group than in the CS group. The scar widths were 64.3 ± 14.7 µm and 86.8 ± 12.1 µm in the UPS and CS groups, respectively (P = 0.03). The scar areas were 11,398 ± 1595 µm2 in the UPS group and 17,433 ± 3487 µm2 in the CS group (P = 0.014). The UPS group had less inflammation on day 3, less transforming growth factor synthesis on days 3 and 7, lower levels of matrix metalloproteinases, and less collagen synthesis on day 7 than did the CS group. The UPS achieved less local inflammation by reducing the local tissue damage in diabetic rat models, enabling better healing, and resulting in less scar formation. The UPS warrants further clinical study as it may bring beneficial outcomes for patients with impaired healing capability and patients who seek to reduce scarring.

Influence of Platelet-Rich Plasma on Recurrent Vesicovaginal Fistula-A Histological and Immunohistochemical Study.

Vesicovaginal fistula is a cause of deterioration in the quality of life. It is a communication between the bladder and vagina resulting in the uncontrollable leakage of urine through the vagina. Recently, regenerative methods have been used more frequently, and platelet-rich plasma is one of these methods. The functional properties of platelet-rich plasma are based on the synthesis and secretion of multiple growth factors released after platelet activation. The aim of this study was to investigate how platelet-rich plasma influences the condition of the tissue and the healing ability of the urothelium, vaginal epithelium and tissues surrounding the fistulous canal. The study included eight patients who had undergone the Latzko procedure aimed at closing the vesicovaginal fistula. Samples were collected during primary surgery without platelet-rich plasma and after failed surgery, during a second attempt. The specimens were subjected to histological and immunohistochemical evaluation. The histology demonstrated that in platelet-rich plasma patients, greater vascularization and wider subepithelial mucosa layering was observed. Inflammatory infiltration in the subepithelial layer was increased in platelet-rich plasma patients. No localization differences in growth factor proteins were found in either group, but in platelet-rich plasma-patients, the reactions were stronger. It can be concluded that the use of platelet-rich plasma improves the morphological structure of the injected tissues.