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The liver, a pivotal organ in human metabolism, serves as a primary site for heme biosynthesis, alongside bone marrow. Maintaining precise control over heme production is paramount in healthy livers to meet high metabolic demands while averting potential toxicity from intermediate metabolites, notably protoporphyrin IX. Intriguingly, our recent research uncovers a disrupted heme biosynthesis process termed 'porphyrin overdrive' in cancers that fosters the accumulation of heme intermediates, potentially bolstering tumor survival. Here, we investigate heme and porphyrin metabolism in both healthy and oncogenic human livers, utilizing primary human liver transcriptomics and single-cell RNA sequencing (scRNAseq). Our investigations unveil robust gene expression patterns in heme biosynthesis in healthy livers, supporting electron transport chain (ETC) and cytochrome P450 function without intermediate accumulation. Conversely, liver cancers exhibit rewired heme biosynthesis and a massive downregulation of cytochrome P450 gene expression. Notably, despite diminished drug metabolism, gene expression analysis shows that heme supply to the ETC remains largely unaltered or even elevated with patient cancer progression, suggesting a metabolic priority shift. Liver cancers selectively accumulate intermediates, which are absent in normal tissues, implicating their role in disease advancement as inferred by expression analysis. Furthermore, our findings in genomics establish a link between the aberrant gene expression of porphyrin metabolism and inferior overall survival in aggressive cancers, indicating potential targets for clinical therapy development. We provide in vitro proof-of-concept data on targeting porphyrin overdrive with a drug synergy strategy. [ABSTRACT FROM AUTHOR]

Heme, an iron-containing tetrapyrrole, is essential in almost all organisms. Heme biosynthesis needs to be precisely regulated particularly given the potential cytotoxicity of protoporphyrin IX, the intermediate preceding heme formation. Here, we report on the porphyrin intermediate accumulation within the tumor microenvironment (TME), which we propose to result from dysregulation of heme biosynthesis concomitant with an enhanced cancer survival dependence on mid-step genes, a process we recently termed "Porphyrin Overdrive". Specifically, porphyrins build up in both lung cancer cells and stromal cells in the TME. Within the TME's stromal cells, evidence supports cancer-associated fibroblasts (CAFs) actively producing porphyrins through an imbalanced pathway. Conversely, normal tissues exhibit no porphyrin accumulation, and CAFs deprived of tumor cease porphyrin overproduction, indicating that both cancer and tumor-stromal porphyrin overproduction is confined to the cancer-specific tissue niche. The clinical relevance of our findings is implied by establishing a correlation between imbalanced porphyrin production and overall poorer survival in more aggressive cancers. These findings illuminate the anomalous porphyrin dynamics specifically within the tumor microenvironment, suggesting a potential target for therapeutic intervention. [ABSTRACT FROM AUTHOR]

Electrocatalytic water splitting is an essential hydrogen production method for resolving present energy shortage and progress toward more efficient technologies. For this purpose, a versatile and cheap electrocatalysts are the main challenge along the way. In this report, we synthesized vanadium telluride and carbon nanotube (VTe–CNT)‐based nanocomposite via facile hydrothermal route. The VTe–CNTs are characterized by X‐ray diffraction analysis, scanning electron microscopy, energy‐dispersive spectroscopy, Fourier transform infrared spectroscopy, and Brunauer–Emmett–Teller. These characterizations depict nanosphere structures, morphology, and high surface area that maintains high porosity, which are essential for inclusive water‐splitting phenomena in 1.0 M solution of KOH. Additionally, the electrochemical performance of VTe–CNTs has shown best O2 evolution reactions activity with of onset potential of 1.42 V versus reversible hydrogen electrode and required 10 mA/cm2 of current density at 278 mV overpotential, which is excellent among other electrocatalysts, VTe (342 mV@10 mA/cm−2) and CNTs (365 mV@10mA/cm−2). Moreover, VTe–CNT exhibits remarkable stability for almost 20 h. It also requires a low onset potential of 0.05 V with a small Tafel slope of 47 mV/dec for H2 evolution reactions. Hence, this research might facilitate the easy transportation of electrons and open up the new era, serving as an excellent replacement for noble metal–derived materials. [ABSTRACT FROM AUTHOR]

Objective: To determine the clinico-pathological profile in patients with megaloblastic anemia. Study Design: Cross Sectional study. Setting: Department of Pathology, Sheikh Zayed Medical College/Hospital, Rahim Yar Khan. Study Period: June 2022 to July 2023. Material & Methods: The study subjects were 100 patients suffering from megaloblastic anemia. Using convenient sampling technique, blood samples were analyzed for complete blood count (CBC) and peripheral blood morphology followed by serum B12, serum and red cell folate levels and the bone marrow examination. SPSS version 23 was utilized to analyze the data. The results of variables including age, gender, clinical features and hematological profile were analyzed. Results: Out of 100 diagnosed patients of megaloblastic anemia, 51 (51%) were males, whereas 49 (49%) were females. Anemia alone was present in 18(18%), 11(11%) had anemia along with leucopenia, 14 (14%) faced anemia with thrombocytopenia, 57(57%) had pancytopenia while 16(16%) were pallor. Moreover, 01(01%) of the studied patients presented with fatigue and bleeding while 02 (2%) got weight loss. 10(10%) had fatigue accompanying with Pallor. 19(19%) faced pallor associated with fatigue and bleeding. 14(14%) had pallor accompanying with fatigue, Jaundice and weight loss. 37(37%) had pallor along with fatigue, bleeding, weight loss and jaundice. Conclusion: Males were more frequently affected by megaloblastic anaemia than females. The frequent clinical features appreciated were fatigue, pallor, weight loss, bleeding, and jaundice. Common cytopenia was pancytopenia, followed by bicytopenia. [ABSTRACT FROM AUTHOR]

Objectives: To find the association of breastfeeding and the risk of breast cancer in our population. Study Design: Case-control study. Place and Duration of Study: Oncology Ward-4 at Jinnah Postgraduate Medical Center, Karachi Pakistan, from Jun 2018 to Jun 2019. Methodology: All patients with diagnosed Breast Cancer visiting the outpatient department were enrolled in this study. Controls were randomly selected from the community. Demographic characteristics, reproductive history, breastfeeding pattern, and hormonal status of cancer were collected from all participants. Results: Among patients who had a positive history of breastfeeding were three times more likely to develop breast cancer than those with no history of breastfeeding [Odds Ratio 3.315 (95% Confidence Interval: 2.094-5.249)]. 69.7% of participants in our study breastfed for more than 2 years. There was also a weak inverse association between lactation amenorrhea and breast cancer risk. Women who experienced lactation amenorrhea had only half the risk of women who did not experience lactation amenorrhea [Odds Ratio 0.685 (95% of Confidence Interval: 0.397-1.182)]. Conclusion: There was a negative relationship between breast cancer and breastfeeding. Further research should explore the genetic and cultural differences and the risk of breast cancer. [ABSTRACT FROM AUTHOR]

Study Design: Systematic Review and Meta-analysis Objectives: This systematic review and meta-analysis is aimed to assess effectiveness, safety, clinical, functional and radiological outcome of either combined anteroposterior or posterior-only approach in the surgical management of active tubercular disease of paediatric thoracolumbar spine. Methods: A systematic literature search through PubMed, Scopus, Web of Science and Cochrane Library database was performed. Data extraction was undertaken following methodological quality assessment. Results: 9 out of the 182 publications identified, were included for analysis. A total of 247 patients were analysed. Two amongst the 9 studies were retrospective comparative studies evaluating posterior approach with combined anteroposterior approach and were considered for comparative meta-analysis. Blood loss and duration of surgery was significantly higher in the anteroposterior group, as compared to the posterior-only group. There was no significant difference between the 2 groups in terms of post-operative kyphosis angles, final kyphosis angles, number of complications, functional outcome and spinal fusion time. However, all the included studies were non-randomised and retrospective. Only 2 of them had a control group with a high heterogeneity amongst these 2 studies. Conclusion: The inference from the studies included in this review suggests that equivalent results can be achieved with posterior-only approach for thoracolumbar tuberculosis in children as compared to anteroposterior approach, with much lower complexity, reduced blood loss and shorter surgical time. However, due to the high risk of bias and considerable heterogeneity among the studies included, we cannot conclude whether one approach is better than the other. [ABSTRACT FROM AUTHOR]

Introduction: Soft-tissue chondromas are rare, benign cartilaginous tumors predominantly affecting the extremities, often diagnosed in middle-aged individuals without a clear sex predilection. Despite their benign nature, these tumors can pose significant diagnostic challenges due to their slow growth, asymptomatic nature, and potential for mimicking other soft-tissue tumors., Case Report: We report a case of a 27-year-old male with an 8-year history of a progressively enlarging mass on the dorsal aspect of the second toe of the left foot, leading to pain, difficulty in walking, and wearing shoes. Initial clinical examination revealed a firm, non-tender swelling with hypoesthesia over the affected area. Radiographic findings suggested a soft-tissue mass with stippled calcification, while magnetic resonance imaging indicated a large altered signal intensity lesion abutting but not arising from the bone. Fine needle aspiration cytology hinted at a benign mixed tumor/chondroid syringoma. An excisional biopsy was performed, revealing a well-circumscribed tumor with lobules of mature hyaline cartilage, consistent with a diagnosis of soft-tissue chondroma. Post-operative period recovery was uneventful except for local flap necrosis which was managed with skin grafting. There was no recurrence at the 1-year follow-up., Conclusion: Soft-tissue chondromas, while rare and benign, can significantly impact patients' quality of life. Correct diagnosis, involving a comprehensive evaluation and histopathological confirmation, is crucial for effective management and prevention of unnecessary interventions. This case adds valuable insight into the clinical presentation, diagnostic challenges, and management strategies for soft-tissue chondromas., Competing Interests: Conflict of Interest: Nil, (Copyright: © Indian Orthopaedic Research Group.)