Bola Sadashiva Satish Rao

Skeletal muscle constitutes one of the largest tissue compartments in the human body and plays fundamental roles in locomotion, posture maintenance, and metabolic regulation. Muscle homeostasis requires a precise balance between protein synthesis and degradation pathways; disruption of this equilibrium leads to pathological conditions, including sarcopenia and muscle atrophy, which frequently coexist with metabolic disorders such as obesity, Type 2 diabetes mellitus, and metabolic syndrome. Recent advances have identified the gut microbiota as an important regulator of skeletal muscle health, positioning probiotics as potential therapeutic interventions. Among probiotic candidates, Lactobacillus species have been associated with improvements in muscle health through pleiotropic mechanisms, including attenuation of inflammatory signaling, enhancement of mitochondrial biogenesis, modulation of muscle protein turnover, and restoration of the intestinal microbial balance by enriching beneficial bacteria while suppressing pathogenic species. These multifaceted effects translate to improved exercise performance, amelioration of metabolic dysfunction, and prevention of muscle wasting. This review comprehensively evaluates the current evidence supporting Lactobacillus supplementation as a strategy to increase skeletal muscle health and function, examines the underlying molecular mechanisms, and identifies critical research priorities, including strain‐specific characterization, well‐controlled human clinical trials, and mechanistic investigations, to optimize probiotic‐based interventions for muscle‐related disorders.

Purpose: Glioblastoma multiforme (GBM) is an aggressive malignancy with poor prognosis and high morbidity, primarily due to the blood-brain barrier (BBB) limiting the effectiveness of standard chemotherapy. We developed a dual-ligand liposome-based drug delivery system to overcome this challenge by enhancing tumor targeting. Our approach utilizes liposomes loaded with temozolomide (TMZ) and O6-benzylguanine (O6-BG) and conjugated with transferrin and anti-integrin antibodies, enabling them to cross the BBB and deliver drugs directly to the tumor site. Methods: The thin-layer hydration method was employed to prepare ligand-functionalized liposomes. Compared to the free drug combination, the cytotoxic potential of liposomes was estimated using MTT and apoptosis assays. A radioisotope was tagged to assess plasma, brain, and organ distribution in nude mice. Non-invasive bioluminescence imaging was utilized to visualize tumor response. Results: The optimized nanovesicles (187.4 ± 6.5 nm) exhibited prolonged drug release in tumors, contributing to cell death, as demonstrated through in vitro studies. The drug synergistic effect (combination index: 0.3) resulted in a 1.75- and 3.45-fold increase in cytotoxicity against GBM cells compared to the free drug combinations. Gamma scintigraphy indicated prolonged retention at the tumor site with minimal distribution to other vital organs post-12 h treatment. Despite a reduced dose of TMZ, this unique nanoliposome achieved a two-fold reduction in tumor size, as evidenced by a corresponding decrease in the cell proliferation index. Conclusion: This study opens new avenues for enhancing the therapeutic efficacy of drug combinations by optimizing cellular targeting while significantly decreasing systemic toxicity.

Heat‐shock protein 70 (HSP70) and nanotechnology have emerged as promising avenues in glioblastoma multiforme (GBM) therapy, addressing the critical challenges posed by its aggressive nature and therapeutic resistance. HSP70’s dual role in cellular stress response and tumour survival emphasises its potential as both a biomarker and therapeutic target. This review explores the innovative integration of HSP70 with nanotechnology, emphasising advancements in imaging, drug delivery and combination therapies. Nanoparticles, including SPIONs, liposomes, gold nanoparticles and metal–organic frameworks, demonstrate enhanced targeting and therapeutic efficacy through HSP70 modulation. Functionalized nanocarriers exploit HSP70’s tumour‐specific overexpression to improve drug delivery, minimise off‐target effects and overcome the blood–brain barrier. Emerging strategies such as chemophototherapy, immunotherapy and photothermal therapy leverage HSP70’s interactions within the tumour microenvironment, enabling synergistic treatment modalities. The review also highlights translational challenges, including heterogeneity of GBM, regulatory hurdles and variability in the enhanced permeability and retention (EPR) effect. Integrating computational modelling, personalised approaches and adaptive trial designs is crucial for clinical translation. By bridging nanotechnology and molecular biology, HSP70‐targeted strategies hold transformative potential to redefine GBM diagnosis and treatment, offering hope for improved survival and quality of life. Trial Registration: ClinicalTrials.gov identifier: NCT00054041 and NCT04628806

Glioblastoma (GBM) (grade IV glioma) is the most fatal brain tumor, with a median survival of just 14 months despite current treatments. Temozolomide (TMZ), an alkylating agent used with radiation, faces challenges such as systemic toxicity, poor absorption, and drug resistance. To enhance TMZ effectiveness, we developed poly(ethylene glycol) (PEG) liposomes co-loaded with TMZ and O6-benzylguanine (O6-BG) for targeted glioma therapy. These liposomes, prepared using the thin-layer hydration method, had an average size of 146.33 ± 6.75 nm and a negative zeta potential (−49.6 ± 3.1 mV). Drug release was slower at physiological pH, with 66.84 ± 4.62% of TMZ and 69.70 ± 2.88% of O6-BG released, indicating stability at physiological conditions. The liposomes showed significantly higher cellular uptake (p < 0.05) than the free dye. The dual drug-loaded liposomes exhibited superior cytotoxicity against U87 glioma cells, with a lower IC₅₀ value (3.99µg/mL) than the free drug combination, demonstrating enhanced anticancer efficacy. The liposome formulation induced higher apoptosis (19.42 ± 3.5%) by causing sub-G0/G1 cell cycle arrest. The novelty of our study lies in co-encapsulating TMZ and O6-BG within PEGylated liposomes, effectively overcoming drug resistance and improving targeted delivery for glioma treatment.

Gallic acid (GA) is a natural polyhydroxyphenolic compound with antioxidant, antimutagenic, anti-inflammatory, and antineoplastic activities. Cisplatin (CPT) is a platinum-based chemotherapeutic drug, and it is the treatment of choice for breast, ovarian, testicular, head, and neck cancers. However, the use of anticancer drugs has undesirable effects on patients due to associated toxicities. Thus, it is necessary to search for alternatives that reduce unintended side effects and enhance anticancer potential. The use of natural compounds with the conventional chemotherapeutic drug is a new aspect of cancer therapy. In the present study, we evaluated the ability of GA in the modulation of anticancer effects of CPT in human breast adenocarcinoma cells (MCF-7) by performing MTT, apoptosis, clonogenic cell survival, and micronucleus assays. GA and CPT showed significant cytotoxic activities in MCF-7 cells in a dose-dependent manner. In combination therapy (GA 2.5, 5.0, and 10 μg/mL + CPT10 μg/mL), GA synergistically reduced the MCF-7 cell viability in contrast to the individual therapies. Cancer cells death by GA is through the induction of apoptosis as observed in the acridine orange and ethidium bromide dual staining method. The frequency of micronuclei (MN) was decreased significantly (P < 0.001) in combinational therapy, possibly reducing the risk of chemotherapy-induced MN. Moreover, GA in mono or combinational therapy did not induce any cytotoxic effects in normal breast epithelial cells (MCF-10A). GA did not show any significant difference in colony inhibition compared to CPT. This outcome shows its differential effects in normal and cancerous cells. Hence, the combination GA with chemotherapeutic drugs could represent a promising alternative therapy in cancer treatment with minimal side effects.

Microorganisms are the major cause for the failure of root canal treatment, due to the penetration ability within the root anatomy. However, irrigation regimens have at times failed due to the biofilm mode of bacterial growth. Liposomes are vesicular structures of the phospholipids which might help in better penetration efficiency into dentinal tubules and in increasing the antibacterial efficacy. Methods: In the present work, chlorhexidine liposomes were formulated. Liposomal chlorhexidine was characterized by size, zeta potential, and cryo-electron microscope (Cryo-EM). Twenty-one single-rooted premolars were extracted and irrigated with liposomal chlorhexidine and 2% chlorhexidine solution to evaluate the depth of penetration. In vitro cytotoxicity study was performed for liposomal chlorhexidine on the L929 mouse fibroblast cell line. Results: The average particle size of liposomes ranged from 48 ± 4.52 nm to 223 ± 3.63 nm with a polydispersity index value of 50) value of 12.32 ± 3.65 µg/mL and 29.04 ± 2.14 µg/mL (on L929 and 3T3 cells, respectively) and liposomal chlorhexidine exhibited an IC₅₀ value of 37.9 ± 1.05 µg/mL and 85.24 ± 3.22 µg/mL (on L929 and 3T3 cells, respectively). Discussion: Antimicrobial analysis showed a decrease in colony counts of bacteria when treated with liposomal chlorhexidine compared with 2% chlorhexidine solution. Nano-liposomal novel chlorhexidine was less cytotoxic when treated on mouse fibroblast L929 cells and more effective as an antimicrobial agent along with higher penetration ability.

Background: Glioblastoma, or glioblastoma multiforme (GBM), remains a fatal cancer type despite the remarkable progress in understanding the genesis and propagation of the tumor. Current treatment modalities, comprising mainly of surgery followed by adjuvant chemoradiation, are insufficient for improving patients' survival owing to existing hurdles, including the blood–brain barrier (BBB). In contemporary practice, the prospect of long-term survival or cure continues to be a challenge for patients suffering from GBM. This review provides an insight into the drug delivery strategies and the significant efforts made in lipid-based nanoplatform research to circumvent the challenges in optimal drug delivery in GBM.Area covered: Owing to the unique properties of lipid-based nanoplatforms and advancements in clinical translation, this article describes the application of various stimuli-responsive lipid nanocarriers and tumor subcellular organelle-targeted therapy to give an idea about the strategies that can be applied to enhance site-specific drug delivery for GBM. Furthermore, active targeting of drugs via surface-modified lipid-based nanostructures and recent findings in alternative therapeutic platforms such as gene therapy, immunotherapy, and multimodal therapy have also been overviewed.Expert opinion: Lipid-based nanoparticles stand out among the other nanocarriers explored for GBM drug delivery, as they support both passive and active drug targeting by crossing/bypassing the BBB at the same time minimizing toxicity and projects better pharmacological parameters. Although these nanocarriers could be a plausible choice for treating GBM, in-depth research is essential to advance neuro-oncology research and enhance outcomes in patients with brain tumors.