Navigating Opioid Alternatives in Spine Surgery: A Comprehensive Review.

The opioid crisis has significantly impacted pain management practices in spine surgery, prompting a critical reassessment of traditional approaches. While opioids have historically been effective for post-operative pain relief, their widespread use has led to substantial public health challenges, including addiction and overdose. This review explores alternative strategies to opioids in spine surgery, emphasizing non-opioid pharmacological options [e.g., nonsteroidal anti-inflammatory drugs (NSAIDs), muscle relaxants, local anesthetics] and non-pharmacological interventions (e.g., physical therapy, cognitive-behavioral therapy). These alternatives aim to mitigate opioid-related risks while optimizing patient outcomes. Key findings highlight these approaches' efficacy, safety considerations, and practical implications. Recommendations include personalized pain management plans and multidisciplinary collaboration to enhance care delivery. Future directions suggest advancing research in innovative pain management technologies and promoting evidence-based practices to mitigate opioid dependence. Ultimately, integrating these strategies into clinical practice is essential for addressing the opioid crisis and ensuring quality care in spine surgery.

PHF6 suppresses self-renewal of leukemic stem cells in AML.

Acute myeloid leukemia is characterized by uncontrolled proliferation of self-renewing myeloid progenitors accompanied by a differentiation arrest. PHF6 is a chromatin-binding protein mutated in myeloid leukemias, and its isolated loss increases mouse HSC self-renewal without malignant transformation. We report here that Phf6 knockout increases the aggressiveness of Hoxa9-driven AML over serial transplantation, and increases the frequency of leukemia initiating cells. We define the in vivo hierarchy of Hoxa9-driven AML and identify a population that we term the "LIC-e" (leukemia initiating cells enriched) population. We find that Phf6 loss expands the LIC-e population and skews its transcriptome to a more stem-like state; concordant transcriptome shifts are also observed on PHF6 knockout in a human AML cell line and in PHF6 mutant patient samples from the BEAT AML dataset. We demonstrate that LIC-e accumulation in Phf6 knockout AML occurs not due to effects on cell cycle or apoptosis, but due to an increase in the fraction of its progeny that retain LIC-e identity. Our work indicates that Phf6 loss increases AML self-renewal through context-specific effects on leukemia stem cells.

Binding Promiscuity of Therapeutic Factor VIII.

The binding promiscuity of proteins defines their ability to indiscriminately bind multiple unrelated molecules. Binding promiscuity is implicated, at least in part, in the off-target reactivity, nonspecific biodistribution, immunogenicity, and/or short half-life of potentially efficacious protein drugs, thus affecting their clinical use. In this review, we discuss the current evidence for the binding promiscuity of factor VIII (FVIII), a protein used for the treatment of hemophilia A, which displays poor pharmacokinetics, and elevated immunogenicity. We summarize the different canonical and noncanonical interactions that FVIII may establish in the circulation and that could be responsible for its therapeutic liabilities. We also provide information suggesting that the FVIII light chain, and especially its C1 and C2 domains, could play an important role in the binding promiscuity. We believe that the knowledge accumulated over years of FVIII usage could be exploited for the development of strategies to predict protein binding promiscuity and therefore anticipate drug efficacy and toxicity. This would open a mutational space to reduce the binding promiscuity of emerging protein drugs while conserving their therapeutic potency.

Abnormal Morphology and Synaptogenic Signaling in Astrocytes Following Prenatal Opioid Exposure.

In recent decades, there has been a dramatic rise in the rates of children being born after in utero exposure to drugs of abuse, particularly opioids. Opioids have been shown to have detrimental effects on neurons and glia in the central nervous system (CNS), but the impact of prenatal opioid exposure (POE) on still-developing synaptic circuitry is largely unknown. Astrocytes exert a powerful influence on synaptic development, secreting factors to either promote or inhibit synapse formation and neuronal maturation in the developing CNS. Here, we investigated the effects of the partial µ-opioid receptor agonist buprenorphine on astrocyte synaptogenic signaling and morphological development in cortical cell culture. Acute buprenorphine treatment had no effect on the excitatory synapse number in astrocyte-free neuron cultures. In conditions where neurons shared culture media with astrocytes, buprenorphine attenuated the synaptogenic capabilities of astrocyte-secreted factors. Neurons cultured from drug-naïve mice showed no change in synapses when treated with factors secreted by astrocytes from POE mice. However, this same treatment was synaptogenic when applied to neurons from POE mice, indicating a complex neuroadaptive response in the event of impaired astrocyte signaling. In addition to promoting morphological and connectivity changes in neurons, POE exerted a strong influence on astrocyte development, disrupting their structural maturation and promoting the accumulation of lipid droplets (LDs), suggestive of a maladaptive stress response in the developing CNS.

Gaining insights into chronic obstructive pulmonary disease exacerbation through emerging biomarkers and the chronic obstructive pulmonary disease assessment test score.

Chronic obstructive pulmonary disease (COPD), a leading cause of mortality and morbidity, presents significant challenges, particularly with exacerbations, which drastically impact patients' health and healthcare costs. The Global Initiative for Chronic Obstructive Lung Disease guidelines recommend comprehensive assessments beyond spirometry, with the COPD assessment test (CAT) emerging as a pivotal tool. Despite its utility, the relationship between CAT scores and specific biomarkers during exacerbations remains unclear. Hence, this study aims to assess the correlation between the CAT score and specific circulating biomarkers. A cross-sectional study from August 2023 to January 2024 included 59 COPD patients with exacerbations who underwent pulmonary function tests and completed the CAT score assessment. The CAT score cut-off point was set at 20, where a CAT score <20 indicated a low impact on health status and a CAT score ≥20 indicated a high impact on health status. On the same day, measurements of neutrophils, leukocytes, eosinophils, C-reactive protein, and procalcitonin were conducted. Patients with CAT scores ≥20 had significantly higher levels of neutrophils (p=0.001), leukocytes (p=0.006), procalcitonin (p=0.010), and forced expiratory volume in the first second/forced vital capacity (p=0.002), but lower eosinophil levels (p=0.025). A positive correlation existed between total CAT score and neutrophils (p=0.001), leukocytes (p=0.000), and procalcitonin (p=0.010), while eosinophil levels showed a negative correlation (p=0.025). The spirometry parameters showed no correlation with the total CAT score. This study highlights the link between CAT and key inflammatory biomarkers, supporting the use of blood biomarkers to identify COPD patients at risk of exacerbations.

Differential Gene Expression Profiles Involved in the Inflammations Due to COVID-19 and Inflammatory Bowel Diseases and the Investigation of Predictive Biomarkers.

Gastrointestinal manifestations in COVID-19 were attributed to 74-86% of the hospitalised patients due to severe or prolonged pathogenesis. Though it is a respiratory disease, the impact it elicits on the gastrointestinal tract and brain are intense. Inflammatory bowel disease including Crohn's disease and ulcerative colitis are idiopathic inflammatory disorders of the gastrointestinal tract. The intrinsic mechanisms involved in gut inflammations due to a respiratory viral disease can be deciphered when the gene expression profiles of COVID-19 and IBD are compared. The current study utilises an integrated bioinformatics approach to unravel them. The publicly available gene expression profiles of colon transcriptomes infected with COVID-19, Crohn's disease and Ulcerative colitis were retrieved, integrated and analysed for the identification of differentially expressed genes. The inter-relational analysis along with gene annotation and pathway enrichment detailed the functional and metabolic pathways of the genes during normal and diseased conditions. The protein-protein interactions deduced from the STRING database and the identified hub genes predicted potential biomarker candidates for COVID-19, Crohn's disease and ulcerative colitis. The inflammatory response pathways were upregulated and enrichment of chemokine signalling, altered lipid metabolism, coagulation and complement cascades were seen in all three conditions along with impaired transport mechanisms. CXCL11, MMP10, and CFB are predicted to be overexpressed biomarkers, whilst GUCA2A, SLC13A2, CEACAM, and IGSF9 as downregulated novel biomarker candidates for colon inflammations. The three miRNAs hsa-miR-16-5p, hsa-miR-21-5p, and hsa-miR-27b-5p exhibited significant interactions with the upregulated hub genes and four long non-coding RNAs NEAT1, KCNQ1OT1, and LINC00852 capable of regulating miRNA were also predicted. This study offers significant information on the underlying molecular mechanisms of inflammatory bowel disease with identification of potential biomarkers.

Cervical Cytology and Histology Correlation as an Analytic Quality Assurance Exercise: Experience from an Accredited Cytology Laboratory.

Context: The performance parameters of cervical cytology in any accredited cytology laboratory requires implementation of quality control exercise, which ensures acceptable performance by a laboratory. This study aims to assess the analytical aspect of quality control measures by evaluating the frequency and accuracy of epithelial abnormalities as detected in cervical Pap smears using histopathologic diagnosis as the gold standard. Methods: A retrospective diagnostic test study from 2018 to 2020 was conducted. Out of the total 6000 Pap smears, histopathologic correlation was available in 150 cases in the form of colposcopic-directed biopsy (CDB) and loop electrosurgical excision procedure (LEEP) tissue in 105 cases. The quality control measures analyzed were Atypical Squamous Cell: Squamous Intraepithelial Lesion (ASC: SIL) ratio, cyto-histo correlation, and study parameters like sensitivity, specificity, positive predictive value, and negative predictive value of Pap smears as against CDB and LEEP. Results: 4.5% smears were reported as inadequate, 92.3% as Negative for intraepithelial lesion or malignancy (NILM), followed by epithelial abnormality found in 3.21%. The ASC: SIL ratio was 1.3:1. Concordance rate against CDB was 100% in Squamous cell carcinoma (SCC), 82.35% in high-grade squamous intraepithelial lesion (HSIL), 82% in atypical squamous cells of undetermined significance (ASCUS), 65.6% in low-grade squamous intraepithelial lesion (LSIL), and 50% in Atypical Squamous Cell ,High grade Squamous Intraepithelial Lesion can not be ruled out (ASC-H). Total concordance rate was 84.15%. Sensitivity of Pap smear was 65% for LSIL and 82% for HSIL. Specificity, positive predictive value, and negative predictive value were 63.63%, 90%, and 75%, respectively. Concordance rate was 96% with LEEP. Conclusion: Quality control measures give an insight of performance of any accredited cytology laboratory. This exercise needs to be conducted on a regular basis, so that relevant steps can be taken in case of major discrepancy.

New benzisoxazole derivative: A potential corrosion inhibitor for mild steel in 0.5 M hydrochloric acid medium -insights from electrochemical and density functional theory studies.

6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole. HCl (FPBH), a substituted benzisoxazole derivative, was prepared from isonipecotic acid and characterized using various spectroscopic techniques. Using electrochemical examinations such as potentiodynamic polarisation (PDP) and electrochemical impedance spectroscopic (EIS) technique, the corrosion mitigation capabilities of this compound for mild steel (MS) in 0.5 M HCl medium were investigated. Theoretical studies were performed using quantum chemical calculations and density functional theory (DFT). PDP results exhibited the mixed-type behavior of FPBH and showed a maximum efficiency of 94.5 % at 1 × 10-3 M. The development of a protective adsorbed layer of FPBH decreases the corrosion current density (icorr) and corrosion rate (CR). The EIS technique revealed that the rise in the charge transfer resistance (Rct) values and reduction in the thickness of the double-layer capacitance (Cdl) reflected the drop in corrosion rate. The adsorption of FPBH took place through physisorption by conforming Langmuir's isotherm. The DFT method was performed on the optimized structure of FPBH to get additional evidence on the action mode of FPBH with the metal surface.

Factors Affecting Best-Tolerated Dose of Pirfenidone in Patients with Fibrosing Interstitial Lung Disease.

The aim of the study was to examine the best-tolerated dose of pirfenidone, the adverse effects profile, and potential factors other than drug dose influencing the tolerability of pirfenidone in patients with fibrosing interstitial lung diseases (ILDs). We performed an observational retrospective study of 113 patients with IPF and other fibrosing ILDs treated with pirfenidone. Baseline liver function tests (LFTs) and dose escalation of pirfenidone were recorded for all patients. The best-tolerated dose was continued if the patient did not tolerate full dose (2400 mg) despite repeated dose escalation attempts. Potential risk factors such as age, height, weight, body mass index (BMI), body surface area (BSA), gender, smoking, and presence of comorbidities were analyzed between 3 groups of best-tolerated pirfenidone doses: 2400 mg/day vs. <2400 mg/day, 2400 mg/day vs. 1800 mg/day, and 2400 mg/day vs. 1200 mg/day. A total of 24 patients tolerated 2400 mg/day, and 89 patients tolerated <2400 mg/day (43 tolerated 1800 mg/day, 45 tolerated 1200 mg/day and 1 tolerated 600 mg/day). Patients who tolerated 2400 mg/day were taller and had a larger BSA as compared to those tolerating <2400 mg/day. Overall, males tolerated the drug better. Presence of comorbidities or smoking did not affect the tolerance of pirfenidone, except for the presence of cerebrovascular diseases. Various adverse effects did not have any significantly different frequencies between the compared groups. Moreover, 71.7% of patients experienced at least one side effect. 1200 mg/day was the best-tolerated dose in the majority of the patients. Male patients with a larger BSA and greater height showed better tolerability of pirfenidone overall.

Comparative evaluation of semaphorin-4D, peptidylarginine deiminase-2, and matrix metalloproteinase-8 levels of gingival crevicular fluid in periodontally healthy and Stage III periodontitis smoker and non-smoker patients before and after non-surgical periodontal therapy.

BACKGROUND: This study was designed to assess the influence of non-surgical periodontal therapy (NSPT) on gingival crevicular fluid (GCF) levels of semaphorin-4D (SEMA-4D), peptidylarginine deiminase-2 (PAD-2), and matrix metalloproteinase-8 (MMP-8) levels in periodontally healthy, Stage III periodontitis non-smoker and smoker patients. METHODS: Sixty patients were equally divided into three groups, Group I: Periodontally healthy, Group II: Non-smokers with Stage III periodontitis, and Group III: Smokers with Stage III periodontitis. The patients underwent NSPT with clinical and biochemical parameters examined at baseline and 3 months post therapy. GCF was collected for levels of SEMA-4D, PAD-2, and MMP-8 through enzyme-linked immunosorbent assay (ELISA). RESULTS: Greater values of PPD (8.06 ± 0.19 mm), CAL (8.94 ± 0.19 mm), PI (2.58 ± 0.19) while lower PBI (1.39 ± 0.19%) and GI (1.72 ± 0.19) scores were seen in Group III as compared to Group II, which reduced significantly from baseline to 3 months in both the groups after NSPT. Minimum values of SEMA-4D, PAD-2, and MMP-8 levels in GCF were seen for Group I, which increased incrementally to Group II and III. Also, among Group II and III the SEMA-4D, PAD-2, and MMP-8 levels in GCF reduced from baseline to 3 months indicating a favorable response within the tissues. CONCLUSION: Greater levels in GCF of Levels of SEMA-4D, PAD-2, and MMP-8 in Group II and III, which reduced significantly post NSPT, implied that these biomarkers play a pivotal role in the inflammatory process and can be utilized for early diagnosis.

The Roles of Zinc Finger Proteins in Colorectal Cancer.

Despite colorectal cancer remaining a leading worldwide cause of cancer-related death, there remains a paucity of effective treatments for advanced disease. The molecular mechanisms underlying the development of colorectal cancer include altered cell signaling and cell cycle regulation that may result from epigenetic modifications of gene expression and function. Acting as important transcriptional regulators of normal biological processes, zinc finger proteins also play key roles in regulating the cellular mechanisms underlying colorectal neoplasia. These actions impact cell differentiation and proliferation, epithelial-mesenchymal transition, apoptosis, homeostasis, senescence, and maintenance of stemness. With the goal of highlighting promising points of therapeutic intervention, we review the oncogenic and tumor suppressor roles of zinc finger proteins with respect to colorectal cancer tumorigenesis and progression.

Glucagon-Like Peptide-1 Receptors in the Gustatory Cortex Influence Food Intake.

The gustatory cortex (GC) region of the insular cortex processes taste information in manners important for taste-guided behaviors, including food intake itself. In addition to oral gustatory stimuli, GC activity is also influenced by physiological states including hunger. The specific cell types and molecular mechanisms that provide the GC with such abilities are unclear. Glucagon-like peptide 1 (GLP-1) is produced by neurons in the brain, where it can act on GLP-1 receptor-expressing (GLP-1R+) neurons found in several brain regions. In these brain regions, GLP-1R agonism suppresses homeostatic food intake and dampens the hedonic value of food. Here, we report in mice of both sexes that cells within the GC express Glp1r mRNA and further, by ex vivo brain slice recordings, that GC GLP-1R+ neurons are depolarized by the selective GLP-1R agonist, exendin-4. Next we found that chemogenetic stimulation of GLP-1R+ neurons, and also pharmacological stimulation of GC-GLP-1Rs themselves, both reduced homeostatic food intake. When mice were chronically maintained on diets with specific fat contents and then later offered foods with new fat contents, we also found that GLP-1R agonism reduced food intake toward foods with differing fat contents, indicating that GC GLP-1R influences may depend on palatability of the food. Together, these results provide evidence for a specific cell population in the GC that may hold roles in both homeostatic and hedonic food intake.SIGNIFICANCE STATEMENT The present study demonstrates that a population of neurons in the GC region of the insular cortex expresses receptors for GLP-1Rs, these neurons are depolarized by agonism of GLP-1Rs, and GC GLP-1Rs can influence food intake on their activation, including in manners depending on food palatability. This work is significant by adding to our understanding of the brain systems that mediate ingestive behavior, which holds implications for metabolic diseases.

Reversine ameliorates hallmarks of cellular senescence in human skeletal myoblasts via reactivation of autophagy.

Cellular senescence leads to the depletion of myogenic progenitors and decreased regenerative capacity. We show that the small molecule 2,6-disubstituted purine, reversine, can improve some well-known hallmarks of cellular aging in senescent myoblast cells. Reversine reactivated autophagy and insulin signaling pathway via upregulation of Adenosine Monophosphate-activated protein kinase (AMPK) and Akt2, restoring insulin sensitivity and glucose uptake in senescent cells. Reversine also restored the loss of connectivity of glycolysis to the TCA cycle, thus restoring dysfunctional mitochondria and the impaired myogenic differentiation potential of senescent myoblasts. Altogether, our data suggest that cellular senescence can be reversed by treatment with a single small molecule without employing genetic reprogramming technologies.

Efficacy of platelet rich fibrin with and without metformin in the treatment of periodontal osseous defects: a systematic review and meta-analysis.

OBJECTIVE: The systematic review and meta-analysis aimed to evaluate the efficacy of Metformin (MF) with Platelet Rich Fibrin (PRF) over PRF alone in the treatment of periodontal osseous defects. MATERIALS AND METHODS: An extensive electronic search for articles published up to September 2021 was conducted on 'Embase', 'PubMed' and other library databases accompanied with manual searching. Randomized controlled trials (RCTs), comparing MF plus PRF Vs PRF alone in periodontal osseous defects were identified in which periodontal pocket depth (PPD), Clinical attachment level (CAL) and Intrabony defect depth (IBD Depth) were the outcome measures. RESULTS: Four studies compared MF plus PRF vs .PRF alone in periodontal osseous defects. Meta-analysis was carried out for PPD reduction, CAL gain and IBD Depth changes. A standardized mean difference (SMD) of 1.86 for PPD reduction, 1.95 for CAL gain and 1.31 for IBD Depth reduction in all the studies was observed and the findings were statistically significant favouring test group. CONCLUSION: The systematic review indicates supplemental benefits of combination therapy of MF + PRF over monotherapy in resolving periodontal osseous defects. In our quest to achieve maximum regeneration in periodontal osseous defects, combination therapies such as MF + PRF have reported to be better treatment choices over other modalities.

Isolation of moderately halotolerant bacterial strains, associated with coral Porites lutea from Gulf of Kachchh: Antibacterial activity and PHB production.

The marine ecosystem contains a solution for food, shelter, pharmaceutical problems and has a key role in the economy of the country as tourism. The Gulf of Kachchh, known for its high tides and the coral reefs are less explored for its antibiotic activity due to the coral bleaching and diseases. The bacterial strains in the coral Porites lutea are determined to possess antibiotic activity against bacterial strains such as E.coli, P. aeruginosa, S. aureus and S. faecalis. Among thirty bacterial strains isolated from the tissue, skeleton and mucus, two bacterial strains resulted in the better antagonistic activity. The antibiotic compound extracted from both the bacteria elucidated to be 4-[(2E)-4-hydroxypent-2-en-1-yl]-5,6-dihydro-2H-pyran-2-one. Further, through ADMET prediction it was inferred that it is an effective drug lead as it reports less toxicity and better drug-likeliness. The study also includes the effect of Poly Hydroxy Butarate (PHB) production by the isolated bacterial strain.

Meta-analysis of the microbial biomarkers in the gut-lung crosstalk in COVID-19, community-acquired pneumonia and Clostridium difficile infections.

Respiratory infections are the leading causes of mortality and the current pandemic COVID-19 is one such trauma that imposed catastrophic devastation to the health and economy of the world. Unravelling the correlations and interplay of the human microbiota in the gut-lung axis would offer incredible solutions to the underlying mystery of the disease progression. The study compared the microbiota profiles of six samples namely healthy gut, healthy lung, COVID-19 infected gut, COVID-19 infected lungs, Clostridium difficile infected gut and community-acquired pneumonia infected lungs. The metagenome data sets were processed, normalized, classified and the rarefaction curves were plotted. The microbial biomarkers for COVID-19 infections were identified as the abundance of Candida and Escherichia in lungs with Ruminococcus in the gut. Candida and Staphylococcus could play a vital role as putative prognostic biomarkers of community-acquired pneumonia whereas abundance of Faecalibacterium and Clostridium is associated with the C. difficile infections in gut. A machine learning random forest classifier applied to the data sets efficiently classified the biomarkers. The study offers an extensive and incredible understanding of the existence of gut-lung axis during dysbiosis of two anatomically different organs.

Year-long wastewater monitoring for SARS-CoV-2 signals in combined and separate sanitary sewers.

COVID-19 wastewater-based epidemiology has been performed in catchments of various sizes and sewer types with many short-term studies available and multi-seasonal studies emerging. The objective of this study was to compare weekly observations of SARS-CoV-2 genes in municipal wastewater across multiple seasons for different systems as a factor of sewer type (combined, separate sanitary) and system size. Sampling occurred following the first wave of SARS-CoV-2 cases in the study region (June 2020) and continued through the third wave (May 2021), the period during which clinical testing was widely available and different variants dominated clinical cases. The strongest correlations were observed between wastewater N1 concentrations and the cumulative clinical cases reported in the 2 weeks prior to wastewater sampling, followed by the week prior, new cases, and the week after wastewater sampling. Sewer type and size did not necessarily explain the strength of the correlations, indicating that other non-sewer factors may be impacting the observations. In-system sampling results for the largest system sampled are presented for 1 month. Removing wet weather days from the data sets improved even the flow-normalized correlations for the systems, potentially indicating that interpreting results during wet weather events may be more complicated than simply accounting for dilution. PRACTITIONER POINTS: SARS-CoV-2 in wastewater correlated best with total clinical cases reported in 2 weeks before wastewater sampling at the utility level. Study performed when clinical testing was widespread during the year after the first COVID-19 wave in the region. Sewer type and size did not necessarily explain correlation strength between clinical cases and wastewater-based epidemiology results. Removing wet weather days improved correlations for 3/4 utilities studied, including both separate sanitary and combined sewers.

Linking α-synuclein-induced synaptopathy and neural network dysfunction in early Parkinson's disease.

The prodromal phase of Parkinson's disease is characterized by aggregation of the misfolded pathogenic protein α-synuclein in select neural centres, co-occurring with non-motor symptoms including sensory and cognitive loss, and emotional disturbances. It is unclear whether neuronal loss is significant during the prodrome. Underlying these symptoms are synaptic impairments and aberrant neural network activity. However, the relationships between synaptic defects and network-level perturbations are not established. In experimental models, pathological α-synuclein not only impacts neurotransmission at the synaptic level, but also leads to changes in brain network-level oscillatory dynamics-both of which likely contribute to non-motor deficits observed in Parkinson's disease. Here we draw upon research from both human subjects and experimental models to propose a 'synapse to network prodrome cascade' wherein before overt cell death, pathological α-synuclein induces synaptic loss and contributes to aberrant network activity, which then gives rise to prodromal symptomology. As the disease progresses, abnormal patterns of neural activity ultimately lead to neuronal loss and clinical progression of disease. Finally, we outline goals and research needed to unravel the basis of functional impairments in Parkinson's disease and other α-synucleinopathies.

Gene Expression Profiling of Glioblastoma to Recognize Potential Biomarker Candidates.

Glioblastoma is an aggressive malignant tumor of the brain and spinal cord. Due to the blood-brain barrier, the accessibility of its treatments still remains significantly challenging. Unfortunately, the recurrence rates of glioblastoma upon surgery are very high too. Hence, understanding the molecular drivers of disease progression is valuable. In this study, we aimed to investigate the molecular drivers responsible for glioblastoma progression and identify valid biomarkers. Three microarray expression profiles GSE90604, GSE50601, and GSE134470 containing healthy and glioblastoma-affected samples revealed overlapping differentially expressed genes (DEGs). The interrelational pathway enrichment analysis elucidated the halt of cell cycle checkpoints and activation of signaling pathways and led to the identification of 6 predominant hub genes. Validation of hub genes in comparison with The Cancer Genome Atlas datasets identified the potential biomarkers of glioblastoma. The study evaluated two significantly upregulated genes, SPARC (secreted protein acidic and rich in cysteine) and VIM (vimentin) for glioblastoma. The genes CACNA1E (calcium voltage-gated channel subunit alpha1 e), SH3GL2 (SH3 domain-containing GRB2-like 2, endophilin A1), and DDN (dendrin) were identified as under-expressed genes as compared to the normal and pan-cancer tissues along with prominent putative prognostic biomarker potentials. The genes DDN and SH3GL2 were found to be upregulated in the proneural subtype, while CACNA1E in the mesenchymal subtype of glioblastoma exhibits good prognostic potential. The mutational analysis also revealed the benign, possibly, and probably damaging substitution mutations. The correlation between the DEG and survival in glioblastoma was evaluated using the Kaplan-Meier plots, and VIM had a greater life expectancy of 60.25 months. Overall, this study identified key candidate genes that might serve as predictive biomarkers for glioblastoma.

An anxious relationship between Autism Spectrum Disorder and Gut Microbiota: A tangled chemistry?

Autism spectrum disorder (ASD) is a serious multifactorial neurodevelopmental disorder often accompanied by strained social communication, repetitive behaviour, immune dysregulation, and gastrointestinal (GI) issues. Recent studies have recorded a link between dysbiosis in the gut microbiota (gm) and the primary stages of ASD. A bidirectional connection (also called microbiota-gut-brain-axis) exchanges information between the gut bacteria and central nervous system. When the homeostasis of the microenvironment of the gut is dysregulated, it causes oxidative stress, affecting neuronal cells and neurotransmitters, thereby causing neurodevelopmental disorders. Studies have confirmed a difference in the constitution of gut bacteria among ASD cases and their controls. Numerous studies on animal models of ASD have shown altered gm and its association with abnormal metabolite profile and altered behaviour phenotype. This process happens due to an abnormal metabolite production in gm, leading to changes in the immune system, especially in ASD. Hence, this review aims to question the current knowledge on gm dysbiosis and its related GI discomforts and ASD behavioural symptoms and shed light on the possible therapeutic approaches available to deal with this situation. Thereby, though it is understood that more research might be needed to prove an association or causal relationship between gm and ASD, therapy with the microbiome may also be considered as an effective strategy to combat this issue.