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In Silico, In Vitro, and In Vivo Antidiabetic Activity of an Alkaloid, 1, 2-Dimethoxy-12-Methyl-7-(3-Methylbut-2-en-1-yl)-12, 13-Dihydro [1,3] Benzodioxolo [5,6-c] Phenanthridin-13-ol, Isolated From a Zimbabwean Herbal Antidiabetic Medicine.4 weeks agoProtein tyrosine phosphatase 1B (PTP1B) is a crucial drug target for treating diabetes mellitus Type 2 (DMT2) because of its link to insulin resistance. Currently there are no approved clinical drugs targeting PTP1B. Therefore, the present study was aimed at investigating the mode of action of an alkaloid, 1, 2-dimethoxy-12-methyl-7-(3-methylbut-2-en-1-yl)-12, 13-dihydro [1,3] benzodioxolo [5,6-c] phenanthridin-13-ol (1, 2 DMMDBP), previously isolated from a popular Zimbabwean antidiabetic herbal medicine. Molecular docking studies using PDB, 2QBP (catalytic site) and IT48 (allosteric site), in vitro PTP1B enzyme inhibition, and in vivo assays using streptozotocin induced diabetic rats were applied to investigate antidiabetic effect. Drug-like and toxicity properties were evaluated using SwissADME and Protox 3.0 webservers, respectively. Molecular docking results showed that the test compound (1, 2 DMMDBP) has a greater binding affinity (11.1 kcal/mol, rmsd, 0.000 Å) for the allosteric site than the catalytic site (9.6 kcal/mol, rmsd, 0.000 Å). In vitro inhibition assay showed that 1, 2 DMMDBP was more potent (IC50 = 1.10 μM) than that of ursolic acid (IC50 = 7.13 μM). Additionally, in in vivo studies, 1, 2 DMMDBP maintained normal hypoglycemia and mass better than the reference drug metformin. In absorption, distribution, metabolism, and excretion predictive studies, 1, 2 DMMDBP showed good drug-like properties. It did not violate any of Lipinski's classic rules. It showed good physicochemical properties such as absorption, (log of skin permeability (log Kp) value was -4.95), bioavailability with a score of 0.55 and biotransformation by cytochrome-P enzymes CYP1A2 and CYP3A4. Protox 3.0 webserver predicted LD50 value of 1000 mg/kg, showing that it may be toxic if swallowed. Based on the evidence presented, 1, 2 DMMDBP is a highly promising compound in the development of potent and selective allosteric modulator drugs of PTP1B for the treatment of DMT2 upon further studies.DiabetesDiabetes type 2Care/Management
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Green-Synthesized Bio-ZnO Nanoparticle-Integrated PVA-Chitosan-PMMA Nanofibers Enhanced Antimicrobial and Tissue-Regenerative Diabetic Wound Healing.4 weeks agoSkin wound healing involves proliferation, inflammation, regeneration, and remodeling. These processes are severely impaired in diabetes due to advanced glycation end-product accumulation, excessive reactive oxygen species, and vascular dysfunction, requiring multifunctional therapeutic and innovative wound care approaches. Thus, many electrospun polymeric matrices were investigated to enhance wound-healing efficacy; however, few studies have examined ZnO NPs embedded multi-component polymeric nanofibers for diabetic wound healing, where infection, oxidative stress, and delayed regeneration persist as major impediments to diabetic wound repair. Addressing these challenges, this study developed a novel therapeutic strategy using electrospun nanofibers of poly(vinyl alcohol)-chitosan-poly(methyl methacrylate) (PVA-Cs-PMMA) integrated with biogenic zinc oxide nanoparticles (Bio-ZnO NPs) synthesized from Syzygium guineense. Comprehensively characterized using UV-vis, FTIR, XRD, TEM, SEM-EDX, and XPS analyses, confirming nanoscale crystalline structure and strong polymer-nanoparticle interactions. Bio-ZnO NPs exhibited potent antibacterial activity against Staphylococcus aureus (29.38 ± 0.91 mm) and Escherichia coli (27.82 ± 0.95 mm), alongside strong antioxidant performance (IC50 = 11.60 mg mL-1, R2 = 0.966). In vivo diabetic wound demonstrated accelerated healing (≥99% closure in 14 days) with enhanced re-epithelialization and collagen deposition, without histopathological abnormalities in major organs. These findings underscore Bio-ZnO NPs@PVA-Cs-PMMA nanofibers as an effective biomaterial with strong potential for advanced diabetic wound management.DiabetesCare/Management
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Efficacy and safety of perioperative intravenous dexamethasone in type 2 diabetes mellitus patients undergoing total hip arthroplasty: a prospective randomized controlled trial.4 weeks agoThis study aimed to evaluate the efficacy and safety of perioperative intravenous dexamethasone (Dexa) in patients with type 2 diabetes mellitus (T2DM) undergoing total hip arthroplasty (THA).
In this prospective, single-blind randomized trial (Registration No.: MR-45-23-047982; Registration Date: December 7, 2023), 60 T2DM patients undergoing THA were assigned to either the Dexa or control group. Outcomes included white blood cell count (WBC), C-reactive protein (CRP), visual analogue scale (VAS) scores, blood glucose, nausea and vomiting, medication requirements, complications, and hospital stay.
Compared with controls, the Dexa group had lower WBC on postoperative days 2 ~ 3 (day 2: 9.20 ± 1.28 vs.10.56 ± 2.34 × 109/L, P = 0.007; day 3: 8.02 ± 1.34 vs. 9.22 ± 1.49 × 109/L, P = 0.002)and reduced CRP on days 1 ~ 3 (day 1: 38.20 vs. 63.50 mg/L, P = 0.040; day 2: 86.00 vs. 101.50 mg/L, P = 0.010; day 3: 78.00 vs. 95.20 mg/L, P = 0.044). Transient hyperglycemia was observed in the Dexa group on postoperative day 1, with higher median blood glucose (8.90 vs. 8.35 mmol/L, P < 0.01) and peak glucose (11.80 vs. 10.35 mmol/L, P = 0.031) but showed no differences thereafter. VAS pain scores at rest and during activity were lower in the Dexa group on postoperative days 1 ~ 2 (all P < 0.01). Dexa reduced the need for rescue tramadol (4 vs. 12 patients, P = 0.020) and metoclopramide (1 vs. 8 patients, P = 0.026), and lowered PONV incidence (3.33% vs. 23.30%, P = 0.026). Hospital stay was shorter in the Dexa group (5.67 ± 1.13 vs. 6.70 ± 1.29 days, P = 0.002), with no differences in 90-day complications (all P > 0.05).
Perioperative Dexa administration improves early recovery outcomes in patients with T2DM undergoing THA without compromising short-term safety, although it may cause transient hyperglycemia. However, the relatively small sample size, limited follow-up period, and lack of systematic evaluation of potential complications highlight the need for larger, longer-term studies to further strengthen these observations.DiabetesDiabetes type 2Care/Management -
Periodontal inflammation indices in association to systemic diseases.4 weeks agoPeriodontitis is a multifactorial inflammatory disease that has been associated with several systemic inflammatory conditions. Periodontal inflammation indices are quantitative tools used to estimate the inflammatory burden of periodontitis and its potential systemic relevance. The aim of this review was to summarise and critically evaluate the current evidence on periodontal inflammation indices as connecting factors between periodontitis and systemic inflammatory diseases, and to assess their responsiveness to periodontal and systemic therapy.
This narrative review included intervention studies investigating patients with both periodontitis and systemic inflammatory diseases by monitoring the inflammatory status using a periodontal inflammation index. Relevant studies were identified through systematic searches across major electronic databases.
The available evidence is limited and methodologically heterogeneous. Most studies focused on periodontal-inflamed-surface-area (PISA). Intervention studies using PISA have been reported in relation to diabetes mellitus, cardiovascular disease, rheumatoid arthritis, and chronic kidney disease. Several studies indicate that reductions in periodontal inflammatory burden following periodontal or systemic therapy may be accompanied by improvements in selected systemic inflammatory or disease-related parameters. However, these findings are inconsistent and often limited by small sample sizes, short follow-up periods, and inadequate control of confounding factors.
While periodontal inflammation indices provide a biologically plausible framework for quantifying inflammatory burden, the bidirectional relationship between periodontal and systemic inflammation, as well as the long-term impact of therapeutic interventions, remains incompletely understood.
Periodontal inflammation indices may support the assessment of periodontitis as a contributor to systemic inflammatory burden. Although high-quality evidence is limited, periodontal therapy may represent a non-pharmacological adjunct in the management of certain systemic inflammatory diseases. Consequently, it may be worthwhile for various medical disciplines, researchers, and professional organisations to engage in comprehensive discourse and issue official statements concerning periodontal therapy as a primary and secondary prevention for systemic diseases.DiabetesCardiovascular diseasesCare/Management -
Taraxasterol Acetate Attenuates TNF-α-Induced Insulin Resistance via Regulation of Insulin Signaling, Inflammation, and Lipid Metabolism in 3T3-L1 Cells.4 weeks agoInsulin resistance, obesity, and type 2 diabetes mellitus (T2DM) are interrelated metabolic disorders with rising global prevalence. Triterpenes, known for their diverse pharmacological properties, have shown potential in improving insulin sensitivity and exerting antidiabetic and antiobesity effects. This study evaluated the effects of taraxasterol acetate (TXA), a pentacyclic triterpene isolated from Eupatorium ballotaefolium, on TNF-α-induced insulin resistance and lipolysis in mature 3T3-L1 adipocytes. TXA significantly enhanced glucose uptake in insulin-resistant adipocytes by promoting GLUT4 translocation by activating the IRS-1/PI3K/Akt signaling pathway and upregulating AMPK expression. TXA also inhibited NF-κB and JNK signaling, reducing inflammation and mitigated oxidative stress by decreasing intracellular reactive oxygen species (ROS) levels and enhancing antioxidant enzyme activity, including superoxide dismutase (SOD) and catalase (CAT). Moreover, TXA normalized adipokine secretion by increasing leptin and adiponectin levels, and promoted lipid accumulation through the modulation of PPARγ, HSL, ATGL, and Perilipin expression. TXA further improved lipid metabolism by upregulating fatty acid β-oxidation genes (ACOX1, CPT1b) and supported mitochondrial function by enhancing PGC-1α and TFAM expression. Collectively, these findings demonstrate that TXA mitigates TNF-α-induced insulin resistance by improving insulin signaling, suppressing inflammation and oxidative stress, and improving lipid and mitochondrial metabolism. These results suggest that TXA is a promising therapeutic candidate for the prevention and treatment of insulin resistance and related metabolic disorders.DiabetesDiabetes type 2Policy
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Fine-Needle Aspiration Cytology of Ameloblastic Carcinoma: A Diagnostic Challenge.4 weeks agoFine-needle aspiration cytology (FNAC) has been extensively applied in the evaluation of head and neck lesions, yet its role in odontogenic tumors remains underexplored. Ameloblastic carcinoma, a rare malignant odontogenic tumor, combines histologic features of ameloblastoma and carcinoma, posing a diagnostic challenge. We report the case of an 83-year-old woman who presented with a slow-growing, painless swelling over the anterior chin associated with numbness and loosening of teeth. Her medical history included partial mandibulectomy with plating six years prior following a mandibular fracture, though operative records were unavailable. FNAC of the swelling yielded mucinous to reddish-brown aspirate, with cytology revealing basaloid cells arranged in a palisading pattern along with stellate-shaped cells, initially suggestive of ameloblastoma. However, the presence of significant cellular atypia and keratin pearl formation raised suspicion of ameloblastic carcinoma. Based on these findings, a provisional diagnosis of ameloblastic carcinoma was made. The patient subsequently underwent surgical resection with fibular grafting under general anesthesia, and histopathological evaluation confirmed the diagnosis, clearly distinguishing it from its benign counterpart. This case highlights the diagnostic value of FNAC in odontogenic malignancies, demonstrating its potential as a minimally invasive, cost-effective, and reliable tool for preoperative diagnosis. Incorporating FNAC into the diagnostic algorithm for suspected odontogenic tumors may improve surgical planning and overall management, particularly in distinguishing aggressive variants such as ameloblastic carcinoma, thereby reducing recurrence and optimizing prognosis.CancerAccess
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Successful Treatment of Histiocytic Sarcoma in Childhood.4 weeks agoHistiocytic sarcoma (HS) is a rare malignant neoplasm that belongs to malignant histiocytoses. HS primarily occurs in adult males and is exceptionally uncommon in pediatric populations. Extranodal regions represent the most common sites of HS manifestation. Diagnosis necessitates histopathological evidence of neoplasm, along with verification of cellular origin through specialized studies. Here, we describe a case of a three-year-old female toddler with HS in her calf that was successfully treated with the chemotherapy protocol of Langerhans Cell Histiocytosis (LCH)-IV, the International Collaborative Treatment Protocol for Children and Adolescents with LCH, version 1.3.CancerAccess
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Neuroendocrine Tumor of the Cauda Equina: A Report of a Rare Case With Histopathological and Immunohistochemical Correlation.4 weeks agoNeuroendocrine tumors (NETs) of the cauda equina are rare, generally benign neoplasms. Previously known as paragangliomas, they were renamed as neuroendocrine tumors in the 2022 World Health Organization (WHO) classification of neuroendocrine neoplasms. These tumors typically occur in adults; however, cases have been reported in nearly all age groups. This report describes the case of a 29-year-old male patient with chronic lumbar pain and bilateral radicular neuropathic pain. Magnetic resonance imaging (MRI) findings described an extramedullary intradural lesion at the level of L1-L2. Surgical resection was performed, resulting in rapid symptom resolution. Clinical presentation and imaging findings are often nonspecific; therefore, definitive diagnosis relies on histopathological examination and immunohistochemical analysis. The main differential diagnoses include ependymoma, schwannoma, meningioma, and hemangioblastoma. NET of the cauda equina is a rare entity, with only a few cases reported in the literature; therefore, this case report serves as a guide to establish a diagnosis and its possible surgical management for future patients.CancerAccessCare/Management
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Soft Tissue Ewing Sarcoma in a Child: A Rare Localization.4 weeks agoEwing sarcoma (ES) is a primitive neuroectodermal tumor usually located in the bones. The soft tissue as a primary localisation of ES is extremely rare. A few cases have been reported in the literature; the most affected areas are the head, trunk, neck, upper and lower limbs, or even multiple lesions. It is most often a painful and mobile subcutaneous swelling with a soft consistency; metastasis is very rare. Differential diagnosis is made with other small round cell neoplasms. Therapy for ES includes chemotherapy, radiation therapy, and surgery. In this paper, we discuss the findings of a soft tissue ewing sarcoma (STES) located in the right arm in a 14-year-old boy successfully treated in our department of pediatric surgery. The follow-up did not show any sign of recurrence after 24 months.CancerAccess
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Preoperative Balloon Aortic Valvuloplasty in a Nonagenarian With Oral Cancer and Severe Aortic Stenosis: A Case Report.4 weeks agoThe concurrent presence of valvular heart disease and malignancy poses significant therapeutic challenges, particularly in patients of advanced age. Balloon aortic valvuloplasty (BAV) represents one potential option for addressing critical aortic valve disease before oncological intervention, though optimal patient selection criteria remain debated. We present a 90-year-old woman in whom echocardiographic evaluation prior to planned gingival cancer surgery revealed hemodynamically significant aortic valve narrowing. Following multidisciplinary consultation with cardiologists and anesthesiologists, BAV was performed 48 hours prior to the oncological procedure. The valve intervention produced sufficient hemodynamic improvement to permit definitive tumor resection with adequate surgical margins, including prophylactic lymph node clearance. Hospital discharge occurred approximately four weeks postoperatively without major adverse events. To the best of our knowledge, this is the first documented instance of a gingival malignancy resection following BAV. Our experience suggests that BAV may enable curative cancer surgery in carefully selected elderly patients with critical valvular disease who would otherwise face prohibitive operative risk. Nonetheless, additional evidence is necessary to define the appropriate role and safety profile of this staged therapeutic approach.CancerAccess