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Alzheimer's disease (AD) is a major cause of disability and one of the top causes of mortality globally. AD remains a major public health challenge due to its prevalence, impact on patients and caregivers, and the current lack of a cure. In recent years, polyphenols have garnered attention for their potential therapeutic effects on AD. The objective of the study was to establish network pharmacology between selected polyphenols of plant origin and AD. Insilico tools such as SwissADME, ProTox3.0, pkCSM, Swiss Target Prediction, DisGeNET, InterActiVenn, DAVID database, STRING database, Cytoscape/CytoHubba were employed to establish the multi-target potential of the polyphenolic compounds. The present study revealed that out of 17 polyphenols, 10 ligands were found to possess a drug-likeness nature along with desirable pharmacokinetic parameters and a lesser toxicity profile. Also, the results highlighted the possible interactions between the polyphenols and the disease targets involved in AD. Further, this study has shed light on the mTOR pathway and its impact on AD through the autophagic mechanism. Overall, this study indicated that polyphenols could be a better therapeutic option for treating AD. Hence, the consumption of polyphenolic cocktails as a part of the diet could produce more effective outcomes against the disease. Additional studies are warranted in the future to explore additional pathways and genes to provide a comprehensive understanding regarding the usage of the shortlisted polyphenols and their derivatives for the prevention and treatment of AD.

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Bovine milk and colostrum play pivotal roles in the nutritional support of both human and bovine infants. Colostrum, the initial milk secretion, is crucial for neonatal growth, providing essential nutrients, growth factors, immunity, and defense mechanisms through a diverse array of bioactive compounds, including bioactive proteins and peptides. Peptidomics, leveraging the potential health benefits of peptides derived from food and body fluids, has become prominent in contemporary research. Endogenous peptides (EPs) have gained notable scientific and commercial interest due to their potential biofunctional significance in areas such as immune health, antimicrobial, anti-inflammatory, antihypertensive, and antioxidative studies. In this investigation, we aimed to extract and analyze low molecular weight EPs from colostrum using four distinct peptide extraction methods, previously employed for EPs extraction from other bodily fluids. The efficiency of these methods was systematically compared and analysed to identify the most effective extraction technique for maximizing the identification of low molecular weight EPs from colostrum. This study represents a pioneering effort as no prior research has systematically compared different extraction methods for low molecular weight EPs from colostrum. Given the unique physical and chemical composition of colostrum compared to milk and other body fluids, a comprehensive analysis of EPs extraction methods was deemed essential. In the present study, we successfully extracted over 3200 EPs from colostrum using trichloroacetic acid (TCA) and a molecular weight cut off (MWCO) extraction method. The findings of this study revealed the extraction of EPs from colostrum, demonstrating potential inherent bioactivities as predicted by in silico tools.

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The present study focused on preparing rohu egg sauce using optimized conditions through enzymatic and fermentative methods. The enzymatic preparation of rohu egg sauce (ERS) involved homogenizing the eggs in water at a ratio of 1:0.9 (w/v), followed by the addition of salt (20% w/w) and papain (3% w/w). A mixture containing salt (25% w/w), sugar (7.5% w/w), and inoculum (10% (w/v)) of Pediococcus pentosaceus FSBP4-40 was utilized to prepare fermentatively produced rohu egg sauce (FRS). ERS and FRS were then stored at room temperature (25 ± 2 °C) and 37 °C for 180 days. After storage, both sauces were evaluated for their scavenging activity against DPPH, ABTS, and superoxide anion (SOA). The ERS demonstrated significantly higher DPPH, ABTS, and SOA scavenging activity compared to the FRS, with values of 61.61 ± 7.33%, 71.21 ± 2.14%, and 85.11 ± 4.92%, respectively, as opposed to 37.49 ± 5.34, 52.31 ± 1.76%, and 63.09 ± 2.31%. Significant changes were observed in the fatty acid profile of the sauces during 180 day storage. Furthermore, after 180 days, the bacterial counts in the FRS were much lower than in the ERS. Overall, this study highlights the importance of using enzymes and LAB in accelerating the hydrolytic process to produce biofunctional rohu egg sauce.

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The cause of sarcoidosis is unknown, and it affects multiple systems with granulomas. Lung lesions are typical, but extrapulmonary findings, especially lymphadenopathy, are present in a significant number of cases. Isolated renal involvement is rare. The presence of noncaseating granulomas on biopsy is a hallmark of sarcoidosis. We present the case of a 59-year-old male with recurrent renal stones who presented with renal failure. The initial diagnosis was challenging due to normal chest imaging and no pulmonary involvement. However, his delayed presentation of calcinosis cutis, an increase in angiotensin-converting enzyme (ACE) level, and the biopsy of the palm lesion with noncaseating granulomas helped us reach the diagnosis. He was started on prednisolone and achieved remission. The report also intends to show that patients with sarcoidosis can present without lung involvement, and physicians should consider sarcoidosis as their differential diagnosis for idiopathic hypercalcemia even if it has no lung or skin findings.

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In forensic examinations, gunshot injury cases can sometimes present unusual challenges. Typically, a gunshot injury involves an entry wound where the bullet penetrates the body and an exit wound where the bullet exits. If the bullet does not exit the body, it can often be recovered from the body cavity. However, there are instances where the entry wound is identified, but both the exit wound and the bullet appear to be missing. This paper explores such a paradox, where, despite a thorough postmortem examination, neither the bullet nor the exit wound is found. We consider various possibilities and analyze whether this was indeed a gunshot injury. Could the bullet still be inside the body, or might it have taken an unexpected route? This paper aims to clarify this puzzling phenomenon through detailed analysis and underscore the importance of meticulous forensic investigation in complex cases.

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Phenylboronic acid (PBA) is recognized as one of the most promising cancer cell binding modules attributed to its potential to form reversible and dynamic boronic ester covalent bonds. Exploring the advanced chemical versatility of PBA is crucial for developing new anticancer therapeutics. The presence of a specific Lewis acidic boron atom-based functional group and a Π-ring-connected ring has garnered increasing interest in the field of cancer immunotherapy. PBA-derivatized functional biomaterials can form reversible bonds with diols containing cell surface markers and proteins. This review primarily focuses on the following topics: (1) the importance and versatility of PBA, (2) different PBA derivatives with pKa values, (3) specific key features of PBA-mediated biomaterials, and (4) cell surface activity for cancer immunotherapy applications. Specific key features of PBA-mediated materials, including sensing, bioadhesion, and gelation, along with important synthesis strategies, are highlighted. The utilization of PBA-mediated biomaterials for cancer immunotherapy, especially the role of PBA-based nanoparticles and PBA-mediated cell-based therapeutics, is also discussed. Finally, a perspective on future research based on PBA-biomaterials for immunotherapy applications is presented.

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The incidence of heart failure (HF) in India is estimated to be 0.5-1.7 cases per 1,000 people per year, and approximately 4,92,000-1.8 million new cases are detected every year. Despite the high rate of mortality associated with HF, most patients do not receive maximal guideline-directed medical therapy (GDMT). Current guidelines advocate early multidrug combination therapy with four classes of drugs, namely, beta-blockers (BBs), mineralocorticoid receptor antagonists (MRAs), angiotensin receptor-neprilysin inhibitors (ARNIs), and sodium-glucose transport protein 2 inhibitors (SGLT-2is), particularly in patients with heart failure with reduced ejection fraction (HFrEF). ARNIs reduce cardiac morbidity and mortality in patients with HFrEF. However, recent data indicated that only 4.8% of patients with HFrEF receive ARNI in India. Hence, at a national consensus on HF meeting, cardiology experts from India formulated a national consensus on the use of ARNI in HF based on current evidence and guidelines. The consensus states that ARNI should be used early in HF, particularly in de novo patients with HFrEF, and those with acute decompensated heart failure (ADHF), irrespective of the presence of low systolic blood pressure (SBP) or diabetes. Moreover, those with HFrEF on renin-angiotensin-aldosterone system (RAAS) inhibitors should be switched to ARNI to reduce the risk of repeated hospitalization for HF, worsening HF, and cardiac death, and to improve the quality of life (QoL). Starting ARNI during the first hospitalization is preferable, and it is safe and effective across all doses. ARNIs can also be used for secondary benefits in patients with preserved ejection fraction [heart failure with preserved ejection fraction (HFpEF)] and HF with mildly reduced EF [heart failure with mildly reduced ejection fraction (HFmrEF)].

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Background: Community-acquired acute kidney injury (CA-AKI) is a sudden structural damage and loss of kidney function in otherwise healthy individuals outside of hospital settings having high morbidity and mortality rates worldwide. Long-term sequelae of AKI involve an associated risk of progression to chronic kidney disease (CKD). Serum creatinine (SCr), the currently used clinical parameter for diagnosing AKI, varies greatly with age, gender, diet, and muscle mass. In the present study, we investigated the difference in urinary proteomic profile of subjects that recovered (R) and incompletely recovered (IR) from CA-AKI, 4 months after hospital discharge. Methods: Study subjects were recruited from ongoing study of CA-AKI cohort. Patients with either sex or age > 18 years with no underline CKD were enrolled at the time of hospital discharge. Incomplete recovery from CA-AKI was defined as eGFR < 60 mL/min/1.73 m2 or dialysis dependence at 4 months after discharge. Second-morning urine samples were collected, and proteome analysis was performed with LC-MS/MS. Data were analyzed by Proteome Discoverer platform 2.2 (Thermo Scientific) using statistical and various bioinformatics tools for abundance of protein, cellular component, protein class and biological process were analyzed in the recovered and incompletely recovered groups. Results: A total of 28 subjects (14 in each group) were enrolled. Collectively, 2019 peptides and proteins with 30 high-abundance proteins in the incompletely recovered group (R/IR <0.5, abundance ratio adj. p-value <0.05) and 11 high-abundance proteins in the incompletely recovered group (R/IR >2.0, abundance ratio adj. p-value <0.05) were identified. Tissue specificity analysis, GO enrichment analysis, and pathway enrichment analysis revealed significant proteins in both the groups that are part of different pathways and might be playing crucial role in renal recovery during the 4-month span after hospital discharge. Conclusion: In conclusion, this study helped in identifying potential proteins and associated pathways that are either upregulated or downregulated at the time of hospital discharge in incompletely recovered CA-AKI patients that can be further investigated to check for their exact role in the disease progression or repair.

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In newborns, especially premature babies, there is a high association between thrombocytopenia and bleeding, particularly intraventricular hemorrhage, which may be due to immaturity. It was usual clinical practice that neonates should be transfused with higher platelet counts than older children or adults to reduce their risk of bleeding. However, after keen observations, we noticed that bleeding and mortality were more common in newborns who received more platelet transfusions. The mechanisms underlying the adverse effects of platelet transfusions in neonates may be due to higher antigenicity and immunological factors. We know that neonatal platelets are hyporeactive; this hyporeactivity is balanced by factors in the neonatal blood that promote coagulation, such as increased hematocrit, von Willebrand factor, and fibrinogen, which, on balance, leads to normal primary neonatal hemostasis. Platelets are very similar to adults in number, but functional capabilities were less, and for the reasons mentioned above, particularly bleeding time was short. Theologically, neonatal platelet lifespan was high to compensate for less production. We started this review because we observed that many babies were not having bleeding symptoms in some instances of severe thrombocytopenia. Many well-active babies are receiving unnecessary transfusions, as human blood is precious, and many young neonatologists are going on protocol-based excessive transfusions. This stimulated us to write a review.

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Malaria remains a substantial global health challenge, causing preventable illnesses and fatalities. In Nepal, the government has ambitiously targeted achieving malaria-free status by 2025. This study aims to assess the impact of women's roles on health-seeking behavior during suspected malaria fever in the high-risk area of Kanchanpur district, Nepal. This is a cross-sectional analytical design with a mixed-method approach, the research focused on Kanchanpur district, selected from 20 high-risk malaria districts of Nepal. Belauri Municipality within Kanchanpur, identified for its concentration of high and moderate-risk wards, was the specific study area. A random selection process identified 387 households for a comprehensive survey. Face-to-face interviews with household heads were conducted after obtaining written informed consent and ethical approval from the Nepal Health Research Council (March 3, 2023/Ref no.-2041). Data analysis, employing statistical measures such as percentages, frequency, mean, and the Chi-square test, was performed using SPSS version 20. Cultural beliefs regarding women's use of bed nets during menstruation significantly predicted health-seeking behavior (p-value < 0.05). Those endorsing bed net use during menstruation were nearly twice as likely to choose modern health facilities (COR = 1.975, 95% C.I. = 1.134 to 3.439, p = 0.016). Women's involvement in malaria treatment decisions strongly correlated with health-seeking behavior (p-value = 0.001). However, women participating in household decisions for suspected malaria treatment were less likely to choose modern health facilities (COR = 0.327, 95% CI = 0.171-0.627, p = 0.001) compared to those without such a role. The study underscores the complex influence of cultural beliefs and women's decision-making roles on health-seeking behavior. Recognizing and comprehending these factors are vital for crafting effective malaria interventions that align with cultural contexts and consider the nuanced roles of women in health-related decisions.

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Breast cancer is one of the leading causes of death among women globally, making its diagnosis and treatment challenging. The use of nanotechnology for cancer diagnosis and treatment is an emerging area of research. To address this issue, multiwalled carbon nanotubes (MWCNTs) were ligand exchanged with butyric acid (BA) to gain hydrophilic character. The successful functionalization was confirmed by FTIR spectroscopy. Surface morphology changes were observed using SEM, while TEM confirmed the structural integrity of the MWCNTs after functionalization. Particle size, zeta potential, and UV spectroscopy were also performed to further characterize the nanoparticles. The breast cancer aptamer specific to Mucin-1 (MUC-1) was then conjugated with the functionalized MWCNTs. These MWCNTs successfully targeted breast cancer cells (MDA-MB-231) as examined by cellular uptake studies and exhibited a reduction in cancer-induced inflammation, as evidenced by gene transcription (qPCR) and protein expression (immunoblotting) levels. Immunoblot and confocal-based immunofluorescence assay (IFA) indicated the ability of CNTs to induce photothermal cell death of MDA-MB-231 cells. Upon imaging, cancer cells were effectively visualized due to the MWCNTs' ability to act as magnetic resonance imaging (MRI) contrast agents. Additionally, MWCNTs demonstrated photothermal capabilities to eliminate bound cancer cells. Collectively, our findings pave the way for developing aptamer-labeled MWCNTs as viable "theranostic alternatives" for breast cancer treatment.

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BACKGROUND: Intranasal drug delivery shows potential for brain access via olfactory and trigeminal routes. PURPOSE: This work aimed to ensure brain availability of nalbuphine via the nasal route. METHOD: Chitosan based nanoparticles loaded with nalbuphine were successfully prepared using ionic gelation method and characterised. RESULT: SEM results revealed that the nanoparticles were spherical in shape, with an average size of 192.4 ± 11.6 nm. Zeta potential and entrapment efficiency was found 32.8 mV and 88.43 ± 7.75%, respectively. The X-ray diffractometry and DSC results unravel a profound understanding on the physical and thermal characteristics. The in-vitro release of nalbuphine from the nanoparticles was biphasic, with an initial burst release followed by a slow-release profile. In-vitro cell study on HEK-293 cells and microscopic images of brain tissue confirmed the safety profile of formulation. In-vivo efficacy studies on animal confirmed the effectiveness of developed intranasal formulation as compared to the standard therapy. The in-vivo pharmacokinetic studies showed that the prepared nanoparticles were able to efficiently deliver nalbuphine to the brain in comparison to the other body organs. Gamma scintigraphy images showed retention of the drug in the brain. Furthermore, the efficacy studies confirmed that the nanoparticles were found significantly more effective than the marketed formulation in pain management.

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Objective: Our study investigates the impact of copy number variations (CNVs) on Parkinson's disease (PD) pathogenesis using genome-wide data, aiming to uncover novel genetic mechanisms and improve the understanding of the role of CNVs in sporadic PD. Methods: We applied a sliding window approach to perform CNV-GWAS and conducted genome-wide burden analyses on CNV data from 11,035 PD patients (including 2,731 early-onset PD (EOPD)) and 8,901 controls from the COURAGE-PD consortium. Results: We identified 14 genome-wide significant CNV loci associated with PD, including one deletion and 13 duplications. Among these, duplications in 7q22.1, 11q12.3 and 7q33 displayed the highest effect. Two significant duplications overlapped with PD-related genes SNCA and VPS13C, but none overlapped with recent significant SNP-based GWAS findings. Five duplications included genes associated with neurological disease, and four overlapping genes were dosage-sensitive and intolerant to loss-of-function variants. Enriched pathways included neurodegeneration, steroid hormone biosynthesis, and lipid metabolism. In early-onset cases, four loci were significantly associated with EOPD, including three known duplications and one novel deletion in PRKN. CNV burden analysis showed a higher prevalence of CNVs in PD-related genes in patients compared to controls (OR=1.56 [1.18-2.09], p=0.0013), with PRKN showing the highest burden (OR=1.47 [1.10-1.98], p=0.026). Patients with CNVs in PRKN had an earlier disease onset. Burden analysis with controls and EOPD patients showed similar results. Interpretation: This is the largest CNV-based GWAS in PD identifying novel CNV regions and confirming the significant CNV burden in EOPD, primarily driven by the PRKN gene, warranting further investigation.

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Yellow nail syndrome is a rare medical syndrome characterized by the combination of a triad of yellow nails, recurrent pulmonary manifestations, and lymphedema. All three features of the triad may not be present synchronously. The diagnosis is made clinically once other causes have been excluded. Typically, it occurs in individuals who are 50 years old and above. We report a case of yellow nail syndrome in a 62-year-old male who presented with recurrent episodes of difficulty breathing due to pleural effusion. Further examination revealed pitting edema of the bilateral lower extremities. In the later encounter, his nail was found to be yellowish. Excluding other diagnoses like heart failure, fungal infections, autoimmune diseases, and lung cancer, with a typical triad, a diagnosis of yellow nail syndrome was made. He was managed with pleural fluid tapping for pleural effusion, compression stockings for leg edema, and vitamin E for nail changes. The study also intends to highlight current treatment options and alert physicians of this syndrome with such typical findings.

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Achieving high-performance aqueous zinc (Zn)-ion batteries (AZIBs) requires stable and efficient cathode materials capable of reversible Zn-ion intercalation. Although layered vanadium oxides possess high Zn-ion storage capacity, their sluggish kinetics and poor conductivity present significant hurdles for further enhancing the performance of AZIBs. In response to this challenge, a dissolution-regrowth and conversion approach is formulated using metal-organic frameworks (MOFs) as a sacrificial template, which enables the in situ creation of copper vanadium oxides (CuVOx) with porous 1D channels and distinctive nanoarchitectures. Owing to their distinctive structure, the optimized CuVOx cathode experiences a reaction involving the synergistic insertion/extraction of Zn2+, resulting in rapid Zn2+ diffusion kinetics and enhanced electrochemical activity postactivation. Specifically, the activated electrode delivers a reversible capacity of 519 mAh g-1 at 0.5 A g-1 for AZIBs. It is noteworthy that the electrode exhibits a remarkable reversible rate capacity of 220 mAh g-1 at 5 A g-1 with excellent durable cycleability, retaining 88% of its capacity even after 3000 cycles. Various ex situ testing methods endorse the reversible insertion/extraction of Zn2+ in the CuVOx cathode. This study provides a novel insight into high-performance MOF-derived unique structure designs for AZIB electrodes.

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Tropomyosin receptor kinases (Trks) are transmembrane receptor tyrosine kinases named TrkA, TrkB, and TrkC and encoded by the NTRK1, NTRK2, and NTRK3 genes, respectively. These kinases have attracted significant attention and represent a promising therapeutic target for solid tumor treatment due to their vital role in cellular signaling pathways. First-generation TRK inhibitors, i.e., Larotrectinib sulfate and Entrectinib, received clinical approval in 2018 and 2019, respectively. However, the use of these inhibitors was significantly limited because of the development of resistance due to mutations. Fortunately, the second-generation Trk inhibitor Repotrectinib (TPX-0005) was approved by the FDA in November 2023, while Selitrectinib (Loxo-195) has provided an effective solution to this issue. Another macrocycle-based analog, along with many other TRK inhibitors, is currently in clinical trials. Two of the three marketed drugs for NTRK fusion cancers feature a pyrazolo[1,5-a] pyrimidine nucleus, prompting medicinal chemists to develop numerous novel pyrazolopyrimidine-based molecules to enhance clinical applications. This article focuses on a comprehensive review of chronological synthetic developments and the structure-activity relationships (SAR) of pyrazolo[1,5-a]pyrimidine derivatives as Trk inhibitors. This article will also provide comprehensive knowledge and future directions to the researchers working in the field of medicinal chemistry by facilitating the structural modification of pyrazolo [1,5-a]pyrimidine derivatives to synthesize more effective novel chemotherapeutics as TRK inhibitors.

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Pesticides pose a significant threat to aquatic ecosystems due to their persistent nature and adverse effects on biota. The increased detection of pesticides in various water bodies has prompted research into their toxicological impacts and potential remediation strategies. However, addressing this issue requires the establishment of robust regulatory frameworks to determine safe thresholds for pesticide concentrations in water and the development of effective treatment methods. This assessment underscores the complex ecological risks associated with organophosphate pesticides (OPPs) and emphasizes the urgent need for strategic management and regulatory measures. This study presents a detailed examination of the global prevalence of OPPs and their potential adverse effects on aquatic and human life. A comprehensive risk assessment identifies azinphos-methyl, chlorpyrifos, and profenfos as posing considerable ecological hazard to fathead minnow, daphnia magna, and T. pyriformis. Additionally, this review explores the potential efficacy of constructed wetlands (CWs) as a sustainable approach for mitigating wastewater contamination by diverse pesticide compounds. Furthermore, the review assess the effectiveness of CWs for treating wastewater contaminated with pesticides by critically analyzing the removal mechanism and key factors. The study suggests that the optimal pH range for CWs is 6-8, with higher temperatures promoting microbial breakdown and lower temperatures enhancing pollutant removal through adsorption and sedimentation. The importance of wetland vegetation in promoting sorption, absorption, and degradation processes is emphasized. The study emphasizes the importance of hydraulic retention time (HRT) in designing, operating, and maintaining CWs for pesticide-contaminated water treatment. The removal efficiency of CWs ranges from 38% to 100%, depending on factors like pesticide type, substrate materials, reactor setup, and operating conditions.

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The structure and stability of charge-coupled lanthanide-substituted Ca10(PO4)6F2 as a potential fluoride-bearing nuclear waste form for the back-end fuel cycle of Gen-IV molten salt reactor have been studied in detail. Here, calcium fluorapatite (CaFAp) as a model structure was taken for incorporation of trivalent lanthanides (Lns, La-Lu except Pm) in a charge-coupled fashion, i.e., 2Ca2+ = Na+ + Ln3+. In these fluorapatite phases, Na+ is substituted exclusively at nine coordinated sites, Ca1, while Ln3+ is preferentially substituted at seven coordinated sites, Ca2. These compositions are further characterized for the local structure by Fourier transform infrared (FTIR) and Raman spectroscopy. Thermal expansion was measured by high-temperature X-ray diffraction (XRD) and the instantaneous thermal expansion coefficient correlates well with the unsubstituted CaFAp. The heat capacities of these solids were measured by differential scanning calorimetry and drop calorimetry, whereas enthalpies of formation were obtained by high-temperature oxide melt solution calorimetry. The thermodynamic analysis demonstrated that lanthanides having ionic radii closure to Ca2+ (Sm3+ and Gd3+) imparted higher thermodynamic stability to the substituted CaFAp as compared to that of other Ln3+. According to structural and thermodynamic investigations, entropy-stabilized fluorapatite waste from NaPr0.125Nd0.125Sm0.125Eu0.125Gd0.125Tb0.125Dy0.125Ho0.125Ca8(PO4)6F2 (WF-Ln) was successfully synthesized for the first time. Furthermore, electron beam irradiation studies probed by XRD, FTIR, Raman, and X-ray absorption (XAS) spectroscopy implied the radiation resistance nature of this substituted CaFAps up to 20 MGy.

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PURPOSE: Surgical reconstruction of large post-traumatic tibial bone and soft tissue defects following high-energy trauma presents a significant challenge for orthopaedic surgeons. This study aimed to evaluate the functional and radiological outcomes of large post-traumatic tibial bone and soft tissue defects managed by single or double-level bone transport using the Ilizarov technique. MATERIAL & METHODS: 13 patients who underwent treatment for large tibial bone defects (Gustillo IIIa, IIIb, IIIc) along with soft tissue defects with Ilizarov from 2010 to 2020 A.D were included. ASAMI functional and radiological outcomes were assessed at the final follow-up to report the outcome. RESULTS: The mean age was 27.38 (18-48). An average bone defect was 7.69 cm (5-13 cm). Based upon the Gustillo-Anderson classification (GA), 2 (15%) of them were GA - 3 A, 7 (54%) were GA - 3B, and 4 (31%) were GA - 3 C. The average time of distraction was 11.76 weeks (8-16). The average time for the union was 37 weeks (27-48 weeks). The average bone lengthening was 7.69 cm (5-13 cm). The mean final leg length discrepancy (LLD) at the final follow-up was 1.96 cm (0-4 cm). The primary union was achieved in eight cases, and five required bone grafting at the docking site. Using the ASAMI (Association for the Study of the Method of Ilizarov) scoring system, the functional results were excellent in six and good in seven cases, while the bony results were excellent in eight, good in four and fair in one case. CONCLUSION: Good to excellent functional and radiological scores (ASAMI) can be expected when using the Ilizarov frame for simultaneous treatment of the large tibial bone and soft tissue defect when this method is applied with correct principles.

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Laminins are essential components of the basement membranes, expressed in a tissue- and cell-specific manner under physiological conditions. During inflammatory circumstances, such as atherosclerosis, alterations in laminin composition within vessels have been observed. Our study aimed to assess the influence of tumor necrosis factor-alpha (TNF), a proinflammatory cytokine abundantly found in atherosclerotic lesions, on endothelial laminin gene expression and the effects of laminin-332 (LN332) on endothelial cells' behavior. We also evaluated the expression of LN332-encoding genes in human carotid atherosclerotic plaques. Our findings demonstrate that TNF induces upregulation of LAMB3 and LAMC2, which, along with LAMA3, encode the LN332 isoform. Endothelial cells cultured on recombinant LN332 exhibit decreased claudin-5 expression and display a loosely connected phenotype, with an elevated expression of chemokines and leukocyte adhesion molecules, enhancing their attractiveness and adhesion to leukocytes in vitro. Furthermore, LAMB3 and LAMC2 are upregulated in human carotid plaques and show a positive correlation with TNF expression. In summary, TNF stimulates the expression of LN332-encoding genes in human endothelial cells and LN332 promotes an endothelial phenotype characterized by compromised junctional integrity and increased leukocyte interaction. These findings highlight the importance of basement membrane proteins for endothelial integrity and the potential role of LN332 in atherosclerosis.

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