In vitro and in silico investigation of glycyrrhizic acid encapsulated zein nanoparticles: A synergistic targeted drug delivery approach for breast cancer.

This study presents an innovative approach for targeted drug delivery through the development of Glycyrrhizic acid-loaded zein nanoparticles (GA-LNPs) as a proficient carrier system. The juxtaposition of zein, a hydrophobic biological macromolecule as a protein carrier, and Glycyrrhizic acid (GA), a hydrophilic therapeutic compound, exemplifies the adaptability of hydrocolloids within cutting-edge drug delivery systems. The characterization and functional traits of research encompass multifaceted analyses of natural macromolecules, which elucidate the homogeneous and spherical morphology of GA-LNPs with an average size of 170.49 nm. The controlled drug release profile of GA, orchestrated under simulated gastrointestinal conditions, adheres to diffusion-based Higuchi kinetics, reflecting the controlled release of the natural macromolecules. The intermolecular interactions among Zein, GA, and cross-linker EDC, facilitated through molecular dynamics simulations, fortify the structural integrity of the encapsulation matrix. In Vitro studies revealed enhanced cellular uptake of GA-LNPs in MCF-7 breast cancer cells. This cellular internalization was further confirmed through cytotoxicity assessments using MTT and apoptosis assays (fluorescence microscopy), which demonstrated the prominent anticancer effects of GA-LNPs on MCF-7 in time/dose-dependent manner. The successful formulation of GA-LNPs, coupled with their sustained release and potent anticancer properties, makes them a potential platform for advanced targeted therapeutic strategies in biomedical applications.

Synthesis, physiochemical characterization, molecular docking study, and anti-breast cancer activity of silymarin loaded zein nanoparticles.

Breast cancer is a major cause of death in women worldwide leading to requirement of new therapeutic strategies. Silymarin demonstrated the anti-cancer activity however, due to low bioavailability its use is restricted. This study aimed to improve the solubility of silymarin by developing a silymarin loaded zein nanoparticles (SLNPs) which was stabilized by beta cyclodextrin. Comprehensive physiochemical characterization studies based on DLS, FTIR, UV-Vis Spectroscopy, FE-SEM, TEM, XRD, DSC, NMR and TGA confirmed the successful synthesis of SLNPs via an anti-solvent precipitation method. FE-SEM and TEM images demonstrated the uniform size and spherical shape of nanoparticles with encapsulation and loading efficiencies of 84.32 ± 1.9 % and 15.25 ± 2.4 % respectively. The zein protein interaction with silymarin, and ß-cyclodextrin was shown to be beneficial via the use of molecular simulations and binding energy calculations. Cellular studies demonstrated dose and time dependent cytotoxicity of SLNPs on MCF-7 breast cancer cell. FACS, qRT-PCR and Western blotting showed Bax (pro-apoptotic) upregulation while Bcl-2 (anti-apoptotic) downregulation. Our findings suggest that these loaded nanoparticles are more efficient than pure drug, enhancing its bioavailability and paving the path for developing it as a promising nutraceutical to treat breast cancer.

Silymarin prevents endothelial dysfunction by upregulating Erk-5 in oxidized LDL exposed endothelial cells.

Extracellular signal-regulated kinase (Erk)-5 is a key mediator of endothelial cell homeostasis, and its inhibition causes loss of critical endothelial markers leading to endothelial dysfunction (ED). Circulating oxidized low-density lipoprotein (oxLDL) has been identified as an underlying cause of ED and atherosclerosis in metabolic disorders. Silymarin (Sym), a flavonolignan, possesses various pharmacological activities however its preventive mechanism in ED warrants further investigation. Here, we have examined the effects of Sym in regulating the expression of Erk-5 and ameliorating ED using in vitro and in vivo models. Primary human umbilical vein endothelial cells (pHUVECs) viability was measured by MTT assay; mRNA and protein expression by RT-qPCR and Western blotting; tube-formation assay was performed to examine endothelialness. In in-vivo experiments, normal chow-fed mice (control) or high-fat diet (HFD)-fed mice were administered Sym or Erk-5 inhibitor (BIX02189) and body weight, blood glucose, plasma-LDL, oxLDL levels, and expression of EC markers in the aorta were examined. Sym (5 µg/ml) maintained the viability and tube-formation ability of oxLDL exposed pHUVECs. Sym increased the expression of Erk-5, vWF, and eNOS and decreased ICAM-1 at transcription and translation levels in oxLDL-exposed pHUVECs. In HFD-fed mice, Sym reduced the body weight, blood glucose, LDL-cholesterol, and oxLDL levels, and increased the levels of vWF and eNOS along with Erk-5 and decreased the level of ICAM-1 in the aorta. These data suggest that Sym could be a potent anti-atherosclerotic agent that could elevate Erk-5 level in the ECs and prevent ED caused by oxidized LDL during HFD-induced obesity in mice.

Enhancing apoptosis-mediated anticancer activity of evodiamine through protein-based nanoparticles in breast cancer cells.

In the cutting-edge era of developing precision therapeutics, nanoparticles have emerged as a potent drug delivery system. Altering the size of poorly water-soluble drugs to nanoscale could confer change in their physical properties, including enhanced water solubility and bioavailability. Evodiamine (EVO), a natural indolequinone alkaloid extract from Evodia rutaecarpa, has shown several important pharmacological applications, anti-cancer being one of them. Protein-based nano-drug delivery systems have gained the interest of researchers due to their better biocompatibility, biodegradability, non-immunogenicity and non-toxicity. In the present study, EVO encapsulated BSA nanoparticles (ENPs) were synthesized and characterized, which were nanoscale-sized (~ 150 nm), monodispersed, spherical shaped, and showed high entrapment efficiency (~ 86%) and controlled drug release. The in-vitro anti-cancer activity of ENPs on human breast cancer cells was dose- and time-dependent. The apoptotic molecular mechanism investigated using FACS, qRT-PCR, and western blotting analysis, revealed increased expression of p53 and Bax and decreased expression of Bcl-2. Biological studies demonstrated comparatively more efficient and targeted delivery of ENPs than pure EVO. The comprehensive physiochemical characterization and in-vitro validation collectively pinpoint ENPs as a promising avenue for harnessing the therapeutic potential of the natural anti-cancer compound EVO. The findings indicate improved cytotoxicity, positioning ENPs as a propitious strategy for advancing breast cancer treatment.

Cigarette smoke-induced galectin-3 as a diagnostic biomarker and therapeutic target in lung tissue remodeling.

Galectin-3 (Gal-3), a multifunctional carbohydrate-binding lectin, has emerged as a key player in various biological processes including inflammation, cancer, cardiovascular diseases and fibrotic disorders, however it remains unclear if Gal-3 is a bystander or drives lung tissue remodeling (LTR). Persistent exposure to cigarette smoke (CS) is the leading cause of oxidative and inflammatory damage to the lung tissues. CS-induced pathological increase in Gal-3 expression has been implicated in the pathogenesis of various respiratory conditions, such as chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), and lung cancer. We and others have reported that CS induces Gal-3 synthesis and secretion, which modulates the pathological signaling pathways in lung epithelial cells implicating Gal-3 as a novel diagnostic marker and a factor driving LTR in CS-exposed lungs. Therefore, pharmacological interventions targeting Gal-3 and its upstream and downstream signaling pathways can help combat CS-induced LTR. Excitingly, preclinical models have demonstrated the efficacy of interventions such as Gal-3 expression inhibition, Gal-3 receptor blockade, and signaling pathways modulation open up promising avenues for future therapeutic interventions. Furthermore, targeting extracellular vesicles-mediated Gal-3 release and the potential of microRNA-based therapy are emerging as novel therapeutic approaches in CS-induced LTR and have been discussed in this article.

Unveiling Scapular Pseudo-winging: A Case Report on Ventral Osteochondroma of the Scapula in a 21-year-old.

Introduction: Scapular pseudo-winging caused by ventral osteochondromas is a rare condition that has been reported in only a handful of cases. This case report describes a 21-year-old male patient with scapular pseudo-winging due to ventral osteochondromas of the scapula. This report adds to the limited literature on this topic and highlights the importance of considering ventral osteochondromas as a possible cause of scapular pseudo-winging. Case Report: A 21-year-old male presented with a swelling on his left upper back that had gradually increased in size over the past 10 years. Physical examination revealed a bony hard swelling arising from the medial border of the scapula, with associated scapular pseudo-winging. Diagnostic imaging confirmed the presence of two ventral osteochondromas located on the body of the scapula. Surgical excision was performed to address the patient's cosmetic concerns. Conclusion: This case report highlights the importance of considering ventral osteochondromas as a possible cause of scapular pseudo-winging. It contributes to the existing literature by documenting a rare presentation and providing insights into the clinical course, diagnostic imaging, and surgical management of this condition. By raising awareness among tumor surgeons and orthopedic surgeons, this report may aid in early recognition and appropriate management of scapular pseudo-winging cases caused by ventral osteochondromas. Furthermore, this report expands our understanding of the etiology and treatment options for scapular pseudo-winging, potentially benefiting patients across various clinical specialties. Categories: Oncology, orthopedics.

Integrating Synthesis, Physicochemical Characterization, and In Silico Studies of Cordycepin-Loaded Bovine Serum Albumin Nanoparticles.

Cordycepin gets rapidly metabolized in the body into inactive form due to its structural similarity to adenosine, thus inhibiting its development as a medicinal agent. This study was aimed to improve the solubility and stability of cordycepin, a potential drug with known antiproliferative activity, by encapsulating it in bovine serum albumin: ß-cyclodextrin nanoparticles. Cordycepin-loaded nanoparticles (CLNPs) were synthesized using the antisolvent method and characterized thoroughly using various techniques. Our dynamic light scattering measurement showed a particle size and zeta potential of 160 ± 2.75 nm and -20.21 ± 2.1 mV, respectively, for CLNPs. Transmission electron microscopy studies revealed that particles were spherical in morphology. These CLNPs showed sustained release of cordycepin with encapsulation and loading efficiency of 81.62 ± 1.5 and 27.02 ± 2.0%, respectively, based on high-performance liquid chromatography and UV-vis studies. Based on differential scanning calorimetry and zeta potential studies, CLNPs improve cordycepin stability and solubility. Our molecular simulations and binding energy calculation also showed favorable protein interaction between cordycepin, bovine serum albumin, and ß-cyclodextrin, further supporting the notion of improved stability. In vitro cytotoxicity, apoptosis, and cellular uptake studies on breast cancer cells showed that the synthesized nanoparticles had greater cytotoxicity as compared to free cordycepin.

Acute-Onset Postoperative Herpetic Endophthalmitis: A Case Report.

Herpes simplex virus uveitis without corneal reactivation is more frequent than previously thought. Although herpes simplex virus has been implicated as a cause of postoperative uveitis and endophthalmitis, it has not been reported as a cause of acute postoperative endophthalmitis within the early postoperative period, specifically within one week following cataract extraction. A 55-year-old man with vascularized irregular central disc-shaped stromal corneal opacity with complicated cataracts underwent cataract surgery. Intraoperatively, there was posterior capsular rent, requiring anterior vitrectomy. On postoperative day three, the patient had an increase in inflammation in the anterior chamber (grade 4+) with marked vitreous haze (grade 4). Vitreous taps were negative for bacteria and fungi, and despite intravitreal injections of vancomycin and ceftazidime, the patient had worsening of inflammation with increasing exudates and the appearance of the fibrinous membrane in the anterior chamber. Polymerase chain reaction (PCR) of aqueous and vitreous samples at this point of time yielded positive serology for herpes viral DNA, and the patient was started on oral valacyclovir. The ocular inflammation resolved soon after switching to oral valacyclovir. Typical acute postoperative endophthalmitis starts two to seven days after surgery, and the most common isolate in vitreous biopsies is coagulase-negative staphylococci. We report a rare case of acute-onset herpetic endophthalmitis presenting within 72 hours following cataract surgery for a complicated cataract in a patient with a history of pre-existing healed viral keratitis. Our case highlights that a suspicion of viral endophthalmitis should be kept in mind as a cause of acute-onset post-cataract surgery endophthalmitis, especially in cases of surgery that fail to yield a positive result on Gram's stain, culture or PCR for bacteria and fungi.

Total external ophthalmoplegia and orbital apex syndrome as first presenting feature of Rhabdomyosarcoma involving petrous part of the temporal bone: A case report.

INTRODUCTION AND IMPORTANCE: Rhabdomyosarcoma (RMS) can have various unusual presentations. We report an unusual presentation of RMS as orbital apex syndrome in a six-year-old boy involving the petrous part of the temporal bone. CASE PRESENTATION: A six-year-old boy presented with drooping of the left eyelid for seven days associated with headache, left-sided hearing loss, and nasal blockage. Contrast-enhanced magnetic resonance imaging (CE-MRI) brain and orbit revealed an ill-defined expansile vascular lesion centered at the petrous part of the left temporal bone with extension to the cavernous sinus, which was confirmed as RMS on histopathology and immunohistochemistry. The patient was managed by chemotherapy and radiotherapy. CLINICAL DISCUSSION: RMS is the most common aggressive malignant soft tissue tumor in the pediatric population. It accounts for 4-8 % of all malignancies in children below 15 years of age, with strong male preponderance. The most common site for RMS is head and neck (45 %), having maximum incidence during the first decade of life. CONCLUSION: Total external ophthalmoplegia in a child is an acute emergency; it should be properly worked up, and neuroimaging should always be advised. Prompt diagnosis and management by a multidisciplinary team can be both life and sight-saving.

Visfatin-induced upregulation of lipogenesis via EGFR/AKT/GSK3ß pathway promotes breast cancer cell growth.

Breast cancer (BC) incidence and associated mortality have increased in tandem with the growth in obesity among the females worldwide. An adipokine, visfatin, has been shown to potentially impact glucose, lipid, and protein metabolism, and promote cancer growth however, the mechanism underlying the effect of visfatin on lipid metabolism dysregulation contributing to BC cell survival, proliferation, and metastasis has not been elucidated. Herein, we have investigated the role of visfatin on the induction of Sterol regulatory element binding protein (SREBP-1) and its upstream and downstream mediators in MCF-7 breast cancer cells. The survival and proliferation was investigated using MTT and Trypan blue assays, cytosolic lipid accumulation was observed using Nile red staining, mRNA and protein expressions were examined using RT-qPCR and western blotting, respectively, and cell cycle analysis was performed using fluorescence-activated cell sorting. Our results indicate that visfatin increased the survival and proliferation of MCF-7 cells in a time- and dose-dependent manner and augmented lipid buildup via activation of SREBP-1 and its associated downstream lipid synthesizing enzymes, at both mRNA and protein levels in MCF-7 cells. Inhibiting SREBP-1 using fatostatin or silencing with siRNA abrogated excessive lipid deposition by suppressing the expression of genes related to lipid synthesis pathway. Further, in-silico study showed high affinity binding of visfatin with epidermal growth factor receptor (EGFR), which was confirmed in an in-vitro study where visfatin increased the phosphorylation of EGFR at tyrosine residue and activated its downstream proteins via phosphorylation of AKT and GSK3ß in MCF-7 cells. Inhibition of GSK3ß by phosphorylation led to increased activity of SREBP-1 and associated downstream proteins. In summary, SREBP-1 may be a critical player in visfatin-induced lipid synthesis and accumulation in BC cells via activation of EGFR/AKT/GSK3ß pathway leading to increased cell survival and proliferation of BC cells.

Cigarette smoke induces epithelial-to-mesenchymal transition, stemness, and metastasis in lung adenocarcinoma cells via upregulated RUNX-2/galectin-3 pathway.

AIMS: An elevated level of galectin-3, a carbohydrate-binding lectin implicated in tumorigenesis, metastasis, and epithelial-mesenchymal transition (EMT), has been found in cigarette smokers. However, the regulation of its expression and role in the pathogenesis of CS-induced EMT and lung cancer metastasis is unclear. Here, we have investigated the mechanism of CS-induced and galectin-3-mediated EMT in airway epithelial cells (AECs). MAIN METHODS: A549 adenocarcinoma cells and primary small airway epithelial cells cultured on an air-liquid interface (ALI) were exposed to cigarette smoke extract (CSE), and MTT, trypan blue, migration, invasion, tumor spheroid and colony formation assays were performed to assess EMT phenotype. Immunoblotting was performed to assess EMT and stemness markers and other regulatory proteins. KEY FINDINGS: CSE exposure affected cell survival and morphology, migration, invasion, and clonogenicity of AECs, which were concomitant with an increase in the expression of EMT markers, galectin-3, and runt-related transcription factor-2 (RUNX-2), an osteogenic transcription factor and upstream regulator of galectin-3. Chemical inhibition or silencing of RUNX-2 downregulated galectin-3 and modulated EMT marker expression, migration, invasion, and clonogenicity in CSE-exposed AECs. Recombinant human galectin-3 also induced EMT and stemness-associated changes in the AECs, and GB1107, a galectin-3 inhibitor, ameliorated these changes. Further, CSE-induced intracellular ROS enabled an increase in RUNX-2 and galectin-3 expression, which were reversed by n-acetyl-cysteine. SIGNIFICANCE: These results provide a novel mechanistic insight into CSE-induced EMT via RUNX-2/galectin-3 axis mediated through ROS, which promoted EMT-associated changes, including invasion, migration, and stemness in AECs, which could be implicated in CS-induced lung cancer progression.

Progress in understanding and improving oil content and quality in seeds.

The world's population is projected to increase by two billion by 2050, resulting in food and energy insecurity. Oilseed crops have been identified as key to address these challenges: they produce and store lipids in the seeds as triacylglycerols that can serve as a source of food/feed, renewable fuels, and other industrially-relevant chemicals. Therefore, improving seed oil content and composition has generated immense interest. Research efforts aiming to unravel the regulatory pathways involved in fatty acid synthesis and to identify targets for metabolic engineering have made tremendous progress. This review provides a summary of the current knowledge of oil metabolism and discusses how photochemical activity and unconventional pathways can contribute to high carbon conversion efficiency in seeds. It also highlights the importance of 13C-metabolic flux analysis as a tool to gain insights on the pathways that regulate oil biosynthesis in seeds. Finally, a list of key genes and regulators that have been recently targeted to enhance seed oil production are reviewed and additional possible targets in the metabolic pathways are proposed to achieve desirable oil content and quality.

Knowledge and attitudes toward the COVID-19 vaccine among India's general rural population.

Introduction: Even after the enforcement of the lockdown, the government was unable to control the spread of the COVID-19 infection. Vaccination is the only remaining hope for preventing and controlling COVID-19 infections. The knowledge and attitude of the recipients can influence vaccine acceptance. In this study, we aim to assess the knowledge and attitude toward the COVID-19 vaccine among the general rural population of India. Methodology: A community-based, prospective, cross-sectional study was conducted from May 2021 to October 2021 in the rural part of the Mandya district of Karnataka, India. Individuals over the age of 18 who met the Ministry of Health and Family Welfare's vaccination eligibility criteria were included in the study. Demographic details of participants and assessment of knowledge and attitude towards the COVID-19 vaccine were done in a designed and validated data collection form. Results: The study included 596 participants, with females dominating males by 54.9 % (327). The average age of the participants was 31 years. Among them, 81.71% (487) had adequate knowledge, and 81.5% (486) had a positive attitude towards the COVID-19 vaccine. Females (85.3%, 279) tend to have a more positive attitude than males (77%, 207). Positive attitude participants (86.86 %, 423) have a higher level of knowledge about the COVID-19 vaccine than negative attitude participants (57.79 %, 63). Conclusion: In the study, we found that 81.71% had adequate knowledge and 81.5% had a positive attitude toward the COVID-19 vaccine.

Introducción: Incluso tras la obligatoriedad del confinamiento el gobierno fue incapaz de controlar la propagación de la infección por COVID-19. La vacuna es la única esperanza que queda para prevenir y controlar las infecciones por COVID-19. El conocimiento y la actitud de los receptores pueden influir en la aceptación de la vacuna. En este estudio, nuestro objetivo fue evaluar el conocimiento y la actitud hacia la vacuna contra la COVID-19 entre la población rural general de India. Metodología: Se realizó un estudio transversal, prospectivo y con base comunitaria de mayo a octubre de 2021 en la zona rural del distrito Mandya de Karnataka, India. Se incluyó en el estudio a los individuos mayores de 18 años que cumplieron los criterios de elegibilidad del Ministerio de Sanidad y Bienestar Familiar. Los datos demográficos de los participantes y la evaluación del conocimiento y la actitud hacia la vacuna contra la COVID-19 se incluyeron en un formulario de recopilación de datos diseñado y validado. Resultados: El estudio incluyó a 596 participantes, siendo más numerosas las mujeres que los hombres en un 54,9 % (327). La edad media de los participantes fue de 31 años. Entre ellos, el 81,71% (487) tenía un conocimiento adecuado, y el 81,5% (486) una actitud positiva hacia la vacuna contra la COVID-19. Las mujeres (85,3%, 279) tendieron a tener una actitud más positiva que los hombres (77%, 207). Los participantes con actitud positiva (86,86 %, 423) tuvieron un mayor nivel de conocimiento sobre la vacuna contra la COVID-19 que los participantes con actitud negativa (57,79 %, 63). Conclusión: En el estudio, encontramos que el 81,71% tuvo un conocimiento adecuado, y el 81,5% una actitud positiva hacia la vacuna contra la COVID-19.

Catheter-associated urinary tract infection: an overview.

CAUTIs (catheter-associated urinary tract infections) continue to be one of the most common health-care-related illnesses in the entire globe. CAUTIs are the cause of 40% of all hospital-acquired infections and 80% of all nosocomial urinary tract infections (UTIs). A urine catheter is implanted into a high percentage of inpatients at some point during their hospitalization, and indwelling urinary catheter adoption likely to be on the rise. Urinary catheters, made of plastic materials, inhibit the urinary tract's natural defence mechanisms and enhance the bacterial colonization or biofilm formation on the catheter surface, which may cause CAUTIs. It is associated with increased burden of disease, mortality, hospital bills and length of hospital stay. Therefore, to prevent these infections, technological innovations in catheter materials that limit biofilm formation will be required. Unfortunately, many health-care practitioners are unclear of the precise indications for bladder catheterization and accurate CAUTI criteria, which can lead to unnecessary catheterization, antibiotic overuse for asymptomatic bacteriuria and the spread of resistant organisms. As a result, we discuss CAUTIs in general, including definitions, pathophysiology, causation, indications for catheterization and a variety of effective CAUTI-fighting strategies.

A Tertiary Care Centre Experience of Recurrent Giant Cell Tumor Around the Knee Joint.

INTRODUCTION: Giant cell tumor (GCT) is a benign but locally aggressive bone tumor. It has a peak incidence between 30-40 years with a predilection for the epiphyseal/metaphyseal region of bone. The most common locations for bone GCT are the distal femur, proximal tibia, distal radius, and sacrum in decreasing order. MATERIAL AND METHODS: In this retrospective study, 22 patients (13 females and nine males) with recurrent giant cell tumors around the knee joint between 2009-2022, with a mean age of 30.2 years (range: 18-55) were included. The patients were followed up monthly for three months, three-monthly for the next two years, six-monthly for the next five years, and thereafter, yearly. The mean follow-up period was 36.97 months (range 23-120 months). RESULTS: There were 19 recurrences after curettages and three after resections. Re-extended curettage was done in 17 cases and the resultant cavities were filled with autologous bone grafts in six and with polymethyl methacrylate (PMMA) cement in the other 11 cases. Reconstruction with megaprosthesis was done in two patients whereas knee arthrodesis was done in two patients after wide resection. The average Musculoskeletal Tumor Society (MSTS) score of our series of 22 patients was 23.1 (Range: 19-30). CONCLUSION: Campanacci grade 1 and 2 lesions can be successfully treated with extended curettage and bone grafting/bone cementing. For patients with grade 3 lesions, there are two options available according to the financial status of the patient; the first option is reconstruction with prosthesis and the other option is arthrodesis.

Intercalary Elbow Resection and Arthrodesis for Giant Cell Tumor of Distal Humerus: Something Is Better Than Nothing.

Giant cell tumor (GCT) of the bone is a benign, locally aggressive neoplasm of epiphyseal origin. Most common sites for GCTs include the distal femur, proximal tibia, and the distal end of radius with the distal humerus being involved rarely. GCT is predominantly managed by extended curettage followed by adjuvant therapy to reduce recurrence. Juxta-articular GCTs are difficult to manage due to the destruction of the articular cartilage and subchondral bone which necessitates the need for joint reconstruction or fusion to salvage the joint. Aggressive and recurrent GCTs can be managed by wide resection of the tumor to reduce local recurrence followed by joint reconstruction or fusion. Joint reconstruction using a total elbow arthroplasty has been described for limb salvage as it provides a good functional outcome. We present a case of an aggressive GCT of the distal humerus that was treated using wide resection with humero-ulnar arthrodesis as an alternative in situations where joint reconstruction is not possible due to the unavailability of the prosthesis or socio-economic factors. The patient was asymptomatic after two years of follow-up, had no signs of recurrence, and had good hand functions.

Recurrent Giant Cell Tumour of Distal End Radius: Treatment and Outcomes After Further Surgeries.

INTRODUCTION: Distal end radius is the second most common location for giant cell tumours (GCTs) followed by the knee. Like at any other location, they are treated with extended curettage or resection but reportedly have an increased propensity for recurrence. This study aims to treat the recurrent distal end radius GCTs and their outcome after further surgeries. PATIENTS AND METHODS: This study was conducted retrospectively from 2009 to 2021 and included 32 patients with recurrent distal end radius GCTs with a mean age of 29.53 years (range: 18-45 years). Twenty-five recurrences occurred after curettage and seven after resection. Twelve lesions were treated with further extended curettage. Nineteen recurrent lesions were treated with resection and arthrodesis. One out of two soft tissue recurrences was treated with en bloc resection. The mean follow-up period was 45.25 months (range: 24-120). RESULTS: The patients with joint preservations treated with further curettage and those where resection of soft tissue recurrences was done with salvage of joint had better functional outcomes with a mean Musculoskeletal Tumor Society (MSTS) score of 26.53 (Range: 22-30). The cases with arthrodesis had an average score of 23.75 (Range: 20-26). The overall average MSTS score was 24.89. CONCLUSIONS: We conclude that local recurrence contained within the bone can be re-curetted. The isolated soft tissue recurrences can be re-excised. The bony lesions with extensive soft tissue extension should be treated with resection and reconstruction. The re-recurrence rate after further adequate treatment does not increase much.

In Vivo Anticancer Evaluation of 6b, a Non-Covalent Imidazo[1,2-a]quinoxaline-Based Epidermal Growth Factor Receptor Inhibitor against Human Xenograft Tumor in Nude Mice.

Tyrosine kinase inhibitors are validated therapeutic agents against EGFR-mutated non-small cell lung cancer (NSCLC). However, the associated critical side effects of these agents are inevitable, demanding more specific and efficient targeting agents. Recently, we have developed and reported a non-covalent imidazo[1,2-a]quinoxaline-based EGFR inhibitor (6b), which showed promising inhibitory activity against the gefitinib-resistant H1975(L858R/T790M) lung cancer cell line. In the present study, we further explored the 6b compound in vivo by employing the A549-induced xenograft model in nude mice. The results indicate that the administration of the 6b compound significantly abolished the growth of the tumor in the A549 xenograft nude mice. Whereas the control mice bearing tumors displayed a declining trend in the survival curve, treatment with the 6b compound improved the survival profile of mice. Moreover, the histological examination showed the cancer cell cytotoxicity of the 6b compound was characterized by cytoplasmic destruction observed in the stained section of the tumor tissues of treated mice. The immunoblotting and qPCR results further signified that 6b inhibited EGFR in tissue samples and consequently altered the downstream pathways mediated by EGFR, leading to a reduction in cancer growth. Therefore, the in vivo findings were in corroboration with the in vitro results, suggesting that 6b possessed potential anticancer activity against EGFR-dependent lung cancer. 6b also exhibited good stability in human and mouse liver microsomes.

Iatrogenic Foot Drop After Anterior Cruciate Ligament Reconstruction With Peroneus Longus Tendon Autograft: Report of a Rare Case.

Reconstruction of the anterior cruciate ligament using autografts is a common procedure performed in the modern era. The peroneus longus tendon is an upcoming graft with several advantages over traditional autografts. It has minimal donor site morbidity in relation to biomechanical properties of the ankle. Common peroneal nerve injury during harvest is a theoretical concern while harvesting the peroneus longus tendon. The following case highlights the importance of careful surgical technique and timely intervention while dealing with such complications. A 25-year-old male suffered an anterior cruciate ligament rupture while wrestling. He had an unstable knee and difficulty performing daily activities. He underwent an arthroscopic anterior cruciate ligament reconstruction using peroneus longus tendon autograft. Following surgery, the patient reported a foot drop and decreased sensations over the dorsum of the foot. The patient was advised of a foot drop splint and neuroprotective medications. Neurophysiological studies were not performed since they cannot differentiate between partial and complete nerve injury in the first week after injury. A surgical exploration of the nerve was done. An intraneural hematoma was found with contusions over the peroneus longus tendon. Neurolysis was performed to decompress the nerve. The functioning of the anterior cruciate ligament was satisfactory during follow-up. An advancing Tinel's sign was noted on follow-up. The patient finally recovered after a 3-month follow-up.