Functional Outcomes of Fluoroscopy-Guided Intra-articular Steroids in Lumbar Facet Arthropathy: A Retrospective Comparative Study of Dexamethasone Versus Triamcinolone Acetonide.

Introduction  Mechanical low back pain frequently originates from the lumbar facet joint (LFJ). Axial low back discomfort can result from osteoarthritis in the LFJ. Depending on the severity of LFJ degeneration, the effect of intra-articular (IA) LFJ corticosteroid injection may vary. For LFJ discomfort, IA block with steroids and local anaesthetics has also been utilised, with varying degrees of success. The main objective of this study was to assess the efficacy of IA steroid injections dexamethasone vs. triamcinolone acetonide for the treatment of LFJ syndrome and to compare functional outcome in terms of Visual Analog Scale (VAS) score, Modified Oswestry Disability Index (MODI) score, and short-form McGill Pain Questionnaire between the two groups. Methodology Dexamethasone 8 mg or triamcinolone acetonide 40 mg was given intra-articularly to 27 patients comprising group A and 33 patients comprising group B, respectively (total 60 patients). Before intervention and at one, three, and six months, observation was conducted using the VAS score, short-form McGill pain questionnaire, and MODI score. Results There was a significant difference between both the groups after the procedure with pain alleviation and functional improvement, more in the group that received triamcinolone acetonide. A significant difference was observed in all three parameters that assessed pain with differences more pronounced at six months. Conclusion Pain reduction and clinical outcomes were better among the group that received triamcinolone acetonide. Injection of a steroid alone is associated with its own side effects. When a lumbar transforaminal epidural injection is used to treat radiculopathy in the lumbar area, particulate medication (triamcinolone) is more effective than non-particulate medication (dexamethasone) with no known drug-related complications.

Periodic DFT calculations to compute the attributes of a quantum material: honeycomb ruthenium trichloride.

Quantum spin liquids (QSLs) have become prominent materials of interest in the pursuit of fault-tolerant materials for quantum computing applications. This is due to the fact that these materials are theorized to host an interesting variety of quantum phenomena such as quasi-particles that may behave as anyons as a result of the high entangled nature of the spin states within the systems. Computing the electronic and magnetic properties of these materials is necessary in order to understand the underlying interactions of the materials. In this paper, the structural, electronic, and magnetic properties including lattice parameters, bandgap, Heisenberg coupling constants, and Curie temperatures for α-RuCl3, a promising candidate for the Kitaev QSL model, are computed using periodic density functional theory. Furthermore, various parameters of the calculations (i.e. functional choice, basis set, k-point density, and Hubbard correction) are varied in order to determine what effect, if any, the computational setup has on the computed properties. The results of this study indicate that PBE functional with Hubbard corrections of 1.5-2.5 eV with a k-point density of 3.0 points per Å-1 appear to be the best parameters to compute Heisenberg coupling constants for α-RuCl3. These parameters with the addition of spin orbit coupling works well for computing Curie temperatures for α-RuCl3. Distinct differences are noted in the computations of the bulk structure vs. monolayer structures, indicating that interactions between the layers play a role in the material properties and changes to the inter-layer spacing may result in interesting and unique magnetic properties that require further investigation.

CRISPR-mediated editing of ß-lactoglobulin (BLG) gene in buffalo.

Milk is a good source of nutrition but is also a source of allergenic proteins such as α-lactalbumin, ß-lactoglobulin (BLG), casein, and immunoglobulins. The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas technology has the potential to edit any gene, including milk allergens. Previously, CRISPR/Cas has been successfully employed in dairy cows and goats, but buffaloes remain unexplored for any milk trait. In this study, we utilized the CRISPR/Cas9 system to edit the major milk allergen BLG gene in buffaloes. First, the editing efficiency of designed sgRNAs was tested in fibroblast cells using the T7E assay and Sanger sequencing. The most effective sgRNA was selected to generate clonal lines of BLG-edited cells. Analysis of 15 single-cell clones, through TA cloning and Sanger sequencing, revealed that 7 clones exhibited bi-allelic (-/-) heterozygous, bi-allelic (-/-) homozygous, and mono-allelic (-/+) disruptions in BLG. Bioinformatics prediction analysis confirmed that non-multiple-of-3 edited nucleotide cell clones have frame shifts and early truncation of BLG protein, while multiple-of-3 edited nucleotides resulted in slightly disoriented protein structures. Somatic cell nuclear transfer (SCNT) method was used to produce blastocyst-stage embryos that have similar developmental rates and quality with wild-type embryos. This study demonstrated the successful bi-allelic editing (-/-) of BLG in buffalo cells through CRISPR/Cas, followed by the production of BLG-edited blastocyst stage embryos using SCNT. With CRISPR and SCNT methods described herein, our long-term goal is to generate gene-edited buffaloes with BLG-free milk.

Promising Combinatorial Therapeutic Strategies against Non-Small Cell Lung Cancer.

Non-small cell lung cancer (NSCLC) presents a complex and diverse disease, exhibiting variations at individuals' cellular and histological levels. This complexity gives rise to different subtypes and genetic mutations, posing challenges for accurate diagnosis and effective treatment. Nevertheless, continuous progress in medical research and therapies is continually shaping the landscape of NSCLC diagnosis and management. The treatment of NSCLC has undergone significant advancements in recent years, especially with the emergence of targeted therapies that have shown remarkable efficacy in patients with actionable mutations. This has ushered in the era of personalized medicine in NSCLC treatment, with improvements in molecular and immunohistochemical techniques contributing to enhanced progression-free survival. This review focuses on the latest progress, challenges, and future directions in developing targeted therapies for NSCLC, including tyrosine kinase inhibitors (TKIs), DNA-damaging agents, immunotherapy regimens, natural drug therapy, and nanobodies. Furthermore, recent randomized studies have demonstrated enhanced overall survival in patients receiving different targeted and natural drug therapies.

Simple fluorochromic detection of chromium with ascorbic acid functionalized luminescent Bio-MOF-1.

The bioaccumulation of various heavy metals in the environment and agriculture is posing serious hazards to human health. Hexavalent chromium is one of the most encountered heavy metal pollutants. The routine monitoring of Cr(VI) via simple methods assumes great analytical significance in sectors like environmental safety, food quality, etc. This study reports a novel biocompatible and luminescent metal-organic framework (ascorbic acid functionalized Bio-MOF-1) based "Turn-on" nanoprobe for rapid and sensitive optical detection of Cr(VI). Bio-MOF-1 has been synthesized, functionalized with ascorbic acid (AA), and then comprehensively characterized for its key material properties. The presence of Cr(VI) results in the photoluminescence recovery of Bio-MOF-1/AA. Using the above approach, Cr(VI) is detected over a wide concentration range of 0.02 to 20 ng mL-1, with the limit of detection being 0.01 ng mL-1. The nanoprobe is capable of detecting Cr(VI) in real water as well as in some spiked food samples. Hence, the ascorbic acid functionalized Bio-MOF-1 nanoprobe is established as a potential on-field detection tool for Cr(VI).

Emerging Trends in Nanotechnology for Endometriosis: Diagnosis to Therapy.

Endometriosis, an incurable gynecological disease that causes abnormal growth of uterine-like tissue outside the uterine cavity, leads to pelvic pain and infertility in millions of individuals. Endometriosis can be treated with medicine and surgery, but recurrence and comorbidities impair quality of life. In recent years, nanoparticle (NP)-based therapy has drawn global attention, notably in medicine. Studies have shown that NPs could revolutionize conventional therapeutics and imaging. Researchers aim to enhance the prognosis of endometriosis patients with less invasive and more effective NP-based treatments. This study evaluates this potential paradigm shift in endometriosis management, exploring NP-based systems for improved treatments and diagnostics. Insights into nanotechnology applications, including gene therapy, photothermal therapy, immunotherapy, and magnetic hyperthermia, offering a theoretical reference for the clinical use of nanotechnology in endometriosis treatment, are discussed in this review.

A Hospital-Based Cross-Sectional Study on the Histopathology of Upper Gastrointestinal Tract Endoscopic Biopsy in Dyspeptic Patients.

Background Dyspepsia is one of the most common GI complaints encountered in clinical practice. Histopathological assessment of endoscopic gastric mucosa biopsy is crucial to delineate the exact cause of dyspepsia to guide patients' management. Objectives The aim of this study was to determine the histopathological spectrum of upper gastrointestinal (GI) tract endoscopic biopsies and to study the age and sex distribution of the predominant upper GI lesions. Methods A cross-sectional study was conducted in the Department of Pathology, Rajendra Institute of Medical Sciences, Ranchi, Jharkhand, India, from January 2022 to December 2023. All endoscopic mucosal biopsies of the esophagus, stomach, and duodenum (first and second parts) lesions were examined under a microscope for histopathological findings. Results Out of 250 endoscopic biopsies studied, there were 76 cases of esophageal biopsies, 149 cases of gastric biopsies, and 25 cases of duodenal biopsies. The male-to-female ratio was 1.2:1. Non-neoplastic lesions were more common than neoplastic lesions. The most common lesions encountered were esophagitis in the esophagus, gastritis in the stomach, and duodenitis in the duodenum. Conclusion The main organic cause of dyspepsia in our setting was chronic gastritis. We conclude that endoscopy of the upper GI tract and histopathological examination help in the earlier detection of both benign and malignant lesions. This aids in better timely management of the patients and improves the overall treatment provided resulting in a better prognosis.

GC-MS analysis of an ethanolic extract of Ocimum species: a network pharmacology analysis insight towards obesity.

Aim: In this study, we have selected two different Ocimum tenuiflorum plants, Ocimum tenuiflorum (Rama tulsi) (OTRT) and Ocimum tenuiflorum (Krishna tulsi) (OTKT). Materials & methods: In the present investigation, ethanol was used as a solvent to estimate the bioactive compounds present in it through gas chromatography-mass spectrometry (GC-MS). Results: Based on the GC-MS data benzenepropanoic acid, 3-methoxy-alpha,4-bis[(trimethylsilyl)oxy was found to be the potent compound in OTRT (MW: 428.74 g/mol) and methyl 3-(4-benzyloxy-3,5-dimethoxyphenyl)-2-methylpropanoate in OTKT (MW: 342.39 g/mol). To estimate its pharmacological application, an integrated Network Pharmacology approach is performed toward the disease target obesity. Conclusion: From the protein-protein interaction from the string database, SRC, BCL2, EGFR, MTOR, CDK1, ERBB2, MAPK1, FYN, AR and MAPK14 are the top-ranked targets.

In silico predicted compound targeting the IQGAP1-GRD domain selectively inhibits growth of human acute myeloid leukemia.

Acute myeloid leukemia (AML) is fatal in the majority of adults. Identification of new therapeutic targets and their pharmacologic modulators are needed to improve outcomes. Previous studies had shown that immunization of rabbits with normal peripheral WBCs that had been incubated with fluorodinitrobenzene elicited high titer antibodies that bound to a spectrum of human leukemias. We report that proteomic analyses of immunoaffinity-purified lysates of primary AML cells showed enrichment of scaffolding protein IQGAP1. Immunohistochemistry and gene-expression analyses confirmed IQGAP1 mRNA overexpression in various cytogenetic subtypes of primary human AML compared to normal hematopoietic cells. shRNA knockdown of IQGAP1 blocked proliferation and clonogenicity of human leukemia cell-lines. To develop small molecules targeting IQGAP1 we performed in-silico screening of 212,966 compounds, selected 4 hits targeting the IQGAP1-GRD domain, and conducted SAR of the 'fittest hit' to identify UR778Br, a prototypical agent targeting IQGAP1. UR778Br inhibited proliferation, induced apoptosis, resulted in G2/M arrest, and inhibited colony formation by leukemia cell-lines and primary-AML while sparing normal marrow cells. UR778Br exhibited favorable ADME/T profiles and drug-likeness to treat AML. In summary, AML shows response to IQGAP1 inhibition, and UR778Br, identified through in-silico studies, selectively targeted AML cells while sparing normal marrow.

Beyond the Eyes: Clinico-Radiological Correlation of Bilateral Complete Horizontal Gaze Palsy in Moebius Syndrome.

Moebius syndrome is a rare disease characterized by unilateral or bilateral facial nerve palsies with/without other cranial nerve palsy. It manifests clinically with facial muscle weakness and/or ophthalmoplegia and can be associated with other physical anomalies such as various limb deformities and orofacial malformation. Herein, we have described the clinical and radiological features of Moebius syndrome in a 9-year-old female child who presented with left-side facial palsy and bilateral complete horizontal gaze palsy.

Comparison Of Ventral Inlay and Dorsal Onlay Urethroplasty For Female Urethral Stricture.

OBJECTIVE: To compare the outcomes of Ventral inlay buccal mucosal graft urethroplasty (VIBMGU) with dorsal onlay buccal mucosal graft urethroplasty (DOBMGU) for the treatment of Female urethral stricture (FUS). MATERIAL AND METHODS: This study included women who underwent either VIBMGU or DOBMGU between January 2016 and June 2023. The preoperative AUA symptom scores, maximal urinary flow rate (Qmax), post-void residual volume (PVR) on ultrasonography, and length and location of the stricture were obtained from a prospectively maintained electronic database. The data obtained from the patient's last visit was compared with the preoperative values for this study. The primary outcome was the success rate. The secondary outcomes were changes in AUA score, PVR, and Qmax. The patient's last follow-up visit was considered for the duration of the follow-up. RESULTS: Seventy-three patients were treated for BMGU for FUS. Forty-six patients underwent VIBMGU, and 27 patients underwent DOBMGU. The median duration of follow-up was 27.5 11.00-55.00) versus 14 (7.00-17.00) months respectively. The success rates of VIBMGU and DOBMGU were 89.13% and 88.89% respectively. There was a reduction in AUA scores and PVR and an improvement in Qmax postoperatively in both groups. The difference in the reduction in AUA scores between the VIBMGU and DOBMGU groups was statistically significant. The difference was not statistically significant in terms of reduction in PVR and improvement in Qmax between the two groups. CONCLUSION: The ventral inlay technique can provide equal results to the dorsal technique with the added advantage of vaginal sparing. This is the single largest series in the literature on female urethral stricture with the largest follow-up period of 90 months.

ZEB1-mediated fibroblast polarization controls inflammation and sensitivity to immunotherapy in colorectal cancer.

The EMT-transcription factor ZEB1 is heterogeneously expressed in tumor cells and in cancer-associated fibroblasts (CAFs) in colorectal cancer (CRC). While ZEB1 in tumor cells regulates metastasis and therapy resistance, its role in CAFs is largely unknown. Combining fibroblast-specific Zeb1 deletion with immunocompetent mouse models of CRC, we observe that inflammation-driven tumorigenesis is accelerated, whereas invasion and metastasis in sporadic cancers are reduced. Single-cell transcriptomics, histological characterization, and in vitro modeling reveal a crucial role of ZEB1 in CAF polarization, promoting myofibroblastic features by restricting inflammatory activation. Zeb1 deficiency impairs collagen deposition and CAF barrier function but increases NFκB-mediated cytokine production, jointly promoting lymphocyte recruitment and immune checkpoint activation. Strikingly, the Zeb1-deficient CAF repertoire sensitizes to immune checkpoint inhibition, offering a therapeutic opportunity of targeting ZEB1 in CAFs and its usage as a prognostic biomarker. Collectively, we demonstrate that ZEB1-dependent plasticity of CAFs suppresses anti-tumor immunity and promotes metastasis.

Psilocybin and 4-Bromo-2,5-Dimethoxyphenethylamine (2C-B) at Encoding Distort Episodic Familiarity.

BACKGROUND: As research on psychedelics (hallucinogenic 5-HT2A agonists) progresses, it is important to delineate the reliability of supposedly unique effects across this drug class. One such effect is how psychedelics impair the formation (i.e., encoding) of hippocampal-dependent recollections (retrieval of specific details) while potentially enhancing the encoding of cortical-dependent familiarity (a feeling of knowing that a stimulus has been previously experienced). METHODS: In a double-blind, placebo-controlled, within-subjects study (N = 20), we tested the acute effects of two distinct psychedelics, psilocybin and 4-bromo-2,5-dimethoxyphenethylamine (2C-B), on the encoding of emotional episodic memories. During acute drug effects, participants viewed negative, neutral, and positive pictures. The following day (while sober), participants completed two separate memory tests for these pictures. RESULTS: Using computational models of memory confidence, we found trends for psilocybin and 2C-B at encoding to impair estimates of recollection that were supported by other measures/analyses. Surprisingly, psilocybin and 2C-B at encoding impaired estimates of familiarity, but these impairments were likely due to a misattribution of heightened familiarity, as both drugs at encoding selectively increased familiarity-based false alarms, especially for negative and positive stimuli. Psilocybin and 2C-B at encoding also tended to impair estimates of metamemory (understanding one's own memory) for negative and neutral memories but enhance estimates of metamemory for positive memories, though these effects were less reliable in additional analyses. CONCLUSIONS: Despite differences in their chemistry, pharmacology, and subjective effects, both psilocybin and 2C-B distort episodic familiarity, alluding to a common neurocognitive mechanism across psychedelics that may drive other phenomena.

Recent Progress on Synthesis of Functionalized 1,5-Disubstituted Triazoles.

Immediately after the invention of 'Click Chemistry' in 2002, the regioselective 1,2,3- triazole scaffolds resulted from respective organic azides and terminal alkynes under Cu(I) catalysis have been well recognized as the functional heterocyclic core at the centre of modern organic chemistry, medicinal chemistry, and material sciences. This CuAAC reaction has several notable features including excellent regioselectivity, high-to-excellent yields, easy to execute, short reaction time, modular in nature, mild condition, readily available starting materials, etc. Moreover, the resulting regioselective triazoles can serve as amide bond isosteres, a privileged functional group in drug discovery and development. More than hundreds of reviews had been devoted to the 'Click Chemistry' in special reference to 1,4-disubstituted triazoles, while only little efforts were made for an opposite regioisomer i.e., 1,5-disubstituted triazole. Herein, we have presented various classical approaches for an expeditious synthesis of a wide range of biologically relevant 1,5- disubstituted 1,2,3-triazole analogues. The syntheses of such a class of diversly functionalized triazoles have emerged as a crucial investigation in the domain of chemistry and biology. This tutorial review covers the literature assessment on the development of various synthetic protocols for the functionalized 1,5-disubstituted triazoles reported during the last 12 years.

N-Hydroxyalkanamide Based Organo/hydrogels as Novel Scaffolds for pH-Dependent Metronidazole and Theophylline Release.

The traditional delivery of metronidazole and theophylline presents challenges like bitter taste, variable absorption, and side effects. However, gel-based systems offer advantages including enhanced targeted drug delivery, minimized side effects, and improved patient compliance, effectively addressing these challenges. Consequently, a cost-effective synthesis of N-hydroxyalkanamide gelators with varying alkyl chain lengths was achieved in a single-step reaction procedure. These gelators formed self-assembled aggregates in DMSO/water solvent system, resulting in organo/hydrogels at a minimum gelation concentration of 1.5 % w/v. Subsequently, metronidazole and theophylline were encapsulated within the gel core and released through gel-to-sol transition triggered by pH variation at 37 °C, while maintaining the structural-activity relationship. UV-vis spectroscopy was employed to observe the drug release behavior. Furthermore, in vitro cytotoxicity assays revealed cytotoxic effects against A549 lung adenocarcinoma cells, indicating anti-proliferative activity against human lung cancer cells. Specifically, the gel containing theophylline (16HAD+Th) exhibited cytotoxicity on cancerous A549 cells with IC50 values of 19.23±0.6 µg/mL, followed by the gel containing metronidazole (16HAD+Mz) with IC50 values of 23.75±0.7 µg/mL. Moreover, the system demonstrated comparable antibacterial activity against both gram-negative (E. coli) and gram-positive bacteria (S. aureus).

Reaction mechanisms for methyl isocyanate (CH3NCO) gas-phase degradation.

Methyl isocyanate (MIC) is a toxic chemical found in many commercial, industrial, and agricultural processes, and was the primary chemical involved in the Bhopal, India disaster of 1984. The atmospheric environmental chemical reactivity of MIC is relatively unknown with only proposed reaction channels, mainly involving OH-initiated reactions. The gas-phase degradation reaction pathways of MIC and its primary product, formyl isocyanate (FIC), were investigated with quantum mechanical (QM) calculations to assess the fate of the toxic chemical and its primary transformation products. Transition state energy barriers and reaction energetics were evaluated for thermolysis/pyrolysis-like reactions and bimolecular reactions initiated by relevant radicals (•OH and Cl•) to evaluate the potential energy surfaces and identify the primary reaction pathways and products. Thermolysis/pyrolysis of MIC requires high energy to initiate N-CH3 and C-H bond dissociation and is unlikely to dissociate except under extreme conditions. Bimolecular radical addition and H-abstraction reaction pathways are deemed the most kinetically and thermodynamically favorable mechanisms. The primary transformation products of MIC were identified as FIC, methylcarbamic acid, isocyanic acid (isocyanate radical), and carbon dioxide. The results of this work inform the gas-phase reaction channels of MIC and FIC reactivity and identify transformation products under various reaction conditions.

Early Injury Landscape in Vein Harvest by Single-Cell and Spatial Transcriptomics.

BACKGROUND: Vein graft failure following cardiovascular bypass surgery results in significant patient morbidity and cost to the healthcare system. Vein graft injury can occur during autogenous vein harvest and preparation, as well as after implantation into the arterial system, leading to the development of intimal hyperplasia, vein graft stenosis, and, ultimately, bypass graft failure. Although previous studies have identified maladaptive pathways that occur shortly after implantation, the specific signaling pathways that occur during vein graft preparation are not well defined and may result in a cumulative impact on vein graft failure. We, therefore, aimed to elucidate the response of the vein conduit wall during harvest and following implantation, probing the key maladaptive pathways driving graft failure with the overarching goal of identifying therapeutic targets for biologic intervention to minimize these natural responses to surgical vein graft injury. METHODS: Employing a novel approach to investigating vascular pathologies, we harnessed both single-nuclei RNA-sequencing and spatial transcriptomics analyses to profile the genomic effects of vein grafts after harvest and distension, then compared these findings to vein grafts obtained 24 hours after carotid-carotid vein bypass implantation in a canine model (n=4). RESULTS: Spatial transcriptomic analysis of canine cephalic vein after initial conduit harvest and distention revealed significant enrichment of pathways (P<0.05) involved in the activation of endothelial cells (ECs), fibroblasts, and vascular smooth muscle cells, namely pathways responsible for cellular proliferation and migration and platelet activation across the intimal and medial layers, cytokine signaling within the adventitial layer, and ECM (extracellular matrix) remodeling throughout the vein wall. Subsequent single-nuclei RNA-sequencing analysis supported these findings and further unveiled distinct EC and fibroblast subpopulations with significant upregulation (P<0.05) of markers related to endothelial injury response and cellular activation of ECs, fibroblasts, and vascular smooth muscle cells. Similarly, in vein grafts obtained 24 hours after arterial bypass, there was an increase in myeloid cell, protomyofibroblast, injury response EC, and mesenchymal-transitioning EC subpopulations with a concomitant decrease in homeostatic ECs and fibroblasts. Among these markers were genes previously implicated in vein graft injury, including VCAN, FBN1, and VEGFC, in addition to novel genes of interest, such as GLIS3 and EPHA3. These genes were further noted to be driving the expression of genes implicated in vascular remodeling and graft failure, such as IL-6, TGFBR1, SMAD4, and ADAMTS9. By integrating the spatial transcriptomics and single-nuclei RNA-sequencing data sets, we highlighted the spatial architecture of the vein graft following distension, wherein activated and mesenchymal-transitioning ECs, myeloid cells, and fibroblasts were notably enriched in the intima and media of distended veins. Finally, intercellular communication network analysis unveiled the critical roles of activated ECs, mesenchymal-transitioning ECs, protomyofibroblasts, and vascular smooth muscle cells in upregulating signaling pathways associated with cellular proliferation (MDK [midkine], PDGF [platelet-derived growth factor], VEGF [vascular endothelial growth factor]), transdifferentiation (Notch), migration (ephrin, semaphorin), ECM remodeling (collagen, laminin, fibronectin), and inflammation (thrombospondin), following distension. CONCLUSIONS: Vein conduit harvest and distension elicit a prompt genomic response facilitated by distinct cellular subpopulations heterogeneously distributed throughout the vein wall. This response was found to be further exacerbated following vein graft implantation, resulting in a cascade of maladaptive gene regulatory networks. Together, these results suggest that distension initiates the upregulation of pathological pathways that may ultimately contribute to bypass graft failure and presents potential early targets warranting investigation for targeted therapies. This work highlights the first applications of single-nuclei and spatial transcriptomic analyses to investigate venous pathologies, underscoring the utility of these methodologies and providing a foundation for future investigations.

Is it possible to treat melanoma by intercepting the CXCR4/CXCL12 pathway?

Melanoma is a particularly aggressive type of skin cancer that can spread to distant organs, resulting in poor patient outcomes. C-X-C motif chemokine ligand 12 (CXCL12) interacts to the C-X-C chemokine receptor type 4 (CXCR4). This connection between CXCR4 and its companion ligand CXCL12 is important in melanoma metastasis and progression, encouraging cell proliferation, invasion, and survival via downstream signaling pathways. Furthermore, CXCR4 is implicated in the interaction between melanoma cells and the tumor microenvironment, which promotes malignant cell migration and immune evasion. Given the importance of the CXCR4/CXCL12 axis in melanoma, addressing this axis has the potential to prevent metastasis and improve patient outcomes. We present an overview of the CXCR4/CXCL12 axis in cancer progression and explain its role in the melanoma microenvironment in this paper. Furthermore, we investigate CXCR4's predictive usefulness as a possible biomarker for monitoring melanoma progression. Finally, we discuss the most recent research and clinical trials on CXCR4 inhibitors, emphasizing their efficacy and limits. We hope to improve the quality of life for melanoma patients by better understanding the role of CXCR4 and investigating novel therapeutic options.

Intraoperative Assessment of Margin Accuracy in Patients Diagnosed With Oral Squamous Cell Carcinoma in a Tertiary Hospital of Jharkhand: Frozen Section Versus Histopathology.

Background The incidence of head and neck carcinoma is increasing. The use of an intraoperative frozen section plays a vital role in the evaluation of margin status in patients undergoing surgery for oral squamous cell carcinoma. A negative margin is not only an indication of successful surgery but also decreases the recurrence of disease and improves the overall survival of patients. Aims and objective The aim of this study is to assess the accuracy of margin in patients undergoing surgery for oral squamous cell carcinoma by intraoperative frozen section and compare it with conventional histopathological examination. Methodology The approach of our study was a hospital-based prospective study conducted on 28 patients diagnosed with oral squamous cell carcinoma. A frozen section was done on all patients undergoing surgery and compared with histopathological examination. Results Out of 28 patients undergoing surgery, the incidence of males was more than females, with a ratio of 6:1. The most common site of the tumor was left buccal mucosa comprising 28.57%, followed by gingivobuccal sulcus comprising 17.85%. In our study, the frozen assessed margin showed a sensitivity of 58.33%, specificity of 98.76%, and accuracy of 95.25%. Conclusion Frozen section is a reliable method for confirmation of margin accuracy and thus reduces the chance of re-surgery and recurrence of disease and increases overall patient survival.

The futuristic applications of transition metal dichalcogenides for cancer therapy.

The second-most common cause of death resulting from genetic mutations in DNA sequences is cancer. The difficulty in the field of anticancer research is the application of the traditional methods, which also affects normal cells. Mutations, genetic replication alterations, and chromosomal abnormalities have a direct impact on the effectiveness of anticancer drugs at different stages. Presently, therapeutic techniques utilize nanotechnology, transition metal dichalcogenides (TMDCs), and robotics. TMDCs are being increasingly employed in tumor therapy and biosensing applications due to their biocompatibility, adjustable bandgap, versatile functionality, exceptional photoelectric properties, and wide range of applications. This study reports the advancement of nanoplatforms based on TMDCs that are specifically engineered for responsive and intelligent cancer therapy. This article offers a thorough examination of the current challenges, future possibilities for theranostic applications using TMDCs, and recent progress in employing TMDCs for cancer therapy. Currently, there is significant interest in two-dimensional (2D) TMDCs nanomaterials as ultrathin unique physicochemical properties. These materials have attracted attention in various fields, including biomedicine. Due to their inherent ability to absorb near-infrared light and their exceptionally large surface area, significant efforts are being made to prepare multifunctional nanoplatforms based on 2D TMDCs.