Hi Tech BioSciences India (India)

The growing limitations of conventional probiotics have driven interest in next-generation probiotics (NGPs), with Clostridium butyricum emerging as a promising candidate due to its spore-forming nature, metabolic adaptability, and therapeutic potential. This study presents a comprehensive characterization of C. butyricum MCC0233, focusing on its probiotic functionality, genomic attributes, and safety profile. In vitro assays revealed significant resilience of MCC0233 to gastrointestinal stress, retaining 20% viability after 2h in simulated gastric fluid and 87.9% after 6h in simulated intestinal fluid. MCC0233 demonstrated strong adhesion to intestinal epithelial cells, 143 ± 4 bacterial cells per 100 HT-29 cells and 241 ± 1 bacterial cells per 100 Caco-2 cells. The strain exhibited high antioxidant activity (82.91%) and significant cholesterol assimilation (67.02%), which is the first report of this property in C. butyricum. It also showed broad-spectrum antimicrobial activity and effective co-aggregation with various enteric pathogens. The whole-genome sequencing revealed a 4.62 Mbp genome with 4,151 protein-coding genes and a GC content of 28.8%. Functional annotation identified genes linked to probiotic traits, including those involved in butyrate production, biosynthesis of branched-chain and aromatic amino acids, and folate (vitamin B9) synthesis. Comparative genomics highlighted strain-specific features contributing to its functional potential. Importantly, both in vitro and in silico safety assessments confirmed the absence of transferable antimicrobial resistance genes, virulence factors, or plasmids. These findings establish C. butyricum MCC0233 as a robust, safe, and multifunctional next-generation probiotic candidate, with promising applications in gut health, metabolic regulation, and microbial therapeutics.

Accelerating the oxygen evolution reaction (OER) entails the dynamic stabilisation of its reaction intermediates to minimise energy barriers and enhance reaction kinetics. Nonetheless, optimisation of adsorption and desorption equilibria remains...

This study aimed to compare efficacy, safety, and immunogenicity of the biosimilar ranibizumab in comparison with the Innovator Ranibizumab in treatment-naive patients with neovascular (wet) age-related macular degeneration (nAMD or wAMD). This comparative, double blind, multicentre, Phase III clinical study randomized eligible patients in a 3:1 ratio to receive either OPTIMAB® (Alkem Laboratories Ltd./ Enzene Biosciences Ltd.) or Innovator Ranibizumab. Intravitreal injections of Innovator Ranibizumab (0.5 mg in 0.05 mL) and OPTIMAB® (0.5 mg in 0.05 mL) were administered every four weeks for 12weeks (three doses). Primary efficacy endpoints included loss of <15 letters from baseline, gain of ≥15 letters from baseline in visual acuity, mean change in best corrected visual acuity (BCVA) from baseline, and change in central subfoveal thickness (CSFT) from baseline at week 12. Safety was assessed through monitoring of adverse events (AEs) and serious adverse events (SAEs) throughout the study. Overall, of the 152 patients randomized, 141 (92.8%) patients (mean age, 66.6 ± 9.37 years) completed the study. Percentage of patients who lost < 15 letters in BCVA at week 12 from baseline was comparable in both the groups (100.0%, each). On secondary end point analysis, the two groups had comparable mean changes in BCVA (OPTIMAB®, 11.8 ± 9.18; innovator ranibizumab, 12.9 ± 10.29; P =0.5509); proportion of patients who gained ≥ 15 letters in visual acuity (OPTIMAB®, 32.18%; innovator ranibizumab, 25.74%; P = 0.4785) and mean change in CSFT (OPTIMAB®, -76.6 ± 89.03; Innovator ranibizumab, -73.1 ± 92.23μm; P = 0.8422) at week 12 as compared to baseline. OPTIMAB® and innovator ranibizumab demonstrated comparable safety over the 12-week treatment period and no patient expressed anti-ranibizumab antibody in either group patient. Biosimilar ranibizumab (OPTIMAB®) was non-inferior to innovator ranibizumab in terms of efficacy, safety, and immunogenicity in the patients of nAMD.

Abstract Research in cancer therapies is rapidly advancing and demands the exploration of innovative approaches to further improve the efficacy of treatment. Here a multimodal approach for cancer therapy is reported which combines bioactive targeting, magnetic hyperthermia, and controlled drug release. For this, a nanoformulation MNP‐Chi‐Dox‐Ab, is bioengineered by conjugating CA 15‐3 antibodies to doxorubicin‐loaded functionalized magnetic nanoparticles (MNPs). Solvothermally synthesized MNPs of uniform spherical shape and size are functionalized with thermo‐pH‐responsive chitosan. The nanoformulation showed higher drug release of ≈65% at pH 5 and 42 °C temperature compared to the release at physiological pH and temperature. Furthermore, in an alternating magnetic field drug release is enhanced to 74%. Cytotoxicity studies in MCF‐7 breast cancer cells confirm the active targeting potential of the nanoformulation. For the nanoformulation without bioactive molecule (anti‐CA 15‐3) only 18% cancer cell death is noted whereas with the conjugation of anti‐CA 15‐3, 43% cell death is recorded. Flow cytometry studies revealed an increased apoptotic population at hyperthermic temperature (42 °C) compared to the physiological temperature. These results suggest that MNP‐Chi‐Dox‐Ab nanoformulation represents a promising multimodal platform for synergistic breast cancer therapy by combining active targeting, controlled drug release, and hyperthermia.

e13053 Background: Vernonia cinerea extract has been known to be used for various haematological disorders including cancer. In the current study, using state-of-the-art extraction and bioanalytical tools we have identified an active compound having anti-tumor properties from the same plant Vernonia cinerea. The crude extract of Vernonia cinerea as well as the active molecule obtained through the chemical route (ENZ302) showed anti-tumor activity against various cancer models including CML, AML, ALL, HER2+ breast cancer, colon cancer, etc. Methods: Various methods including RP-HPLC, XRD, NMR, IR, cell based assay and LC-MS were used to elucidate the molecular structure of ENZ302. MTD, DRF, PK, and Xenograft study etc were carried out in murine model during the preclinical development of ENZ302. Results: ENZ302 resulted significant cytotoxic effect within 8 hrs of treatment in TNBC (Triple Negative Breast Cancer) model, MDA-MB-468 cells when compared with a known inhibitor Lapatinib. However, ENZ302 treatment in primary cells demonstrates no anti-proliferation activity, indicating the specificity of it’s mode of action. Interestingly, a dose-dependent decrease in tumor volumes was observed for ENZ302 in a xenograft model of TNBC while administered orally. ENZ302 did not cause any adverse changes even at 2gm/Kg dose, indicating the safety of the compound. Although a single-dose PK study showed that ENZ302 has a half-life of ̃40 mins, however, in vitro metabolism of the compound in mouse, rat, dog, and human hepatocytes/microsomes showed the molecule is stable in hepatocyte with very low clearance in microsomes (half-life &gt; 30 min), indicating most of the clearance occurring through the kidney. Conclusions: Our preliminary data suggest that ENZ302 is a specific tyrosine kinase (e.g. Src) inhibitor and a promising therapeutic agent against several cancers. A comprehensive proteomic analysis is ongoing to understand the mechanism of action of ENZ302 that makes it effective against several cancers. The discovery of ENZ302 holds ample opportunities to develop a safe and efficacious treatment regimen against several cancers including TNBC.

BackgroundThe human mating system is characterized by bi-parental care and faithful monogamy is highly valued in most cultures. Marriage has evolved as a social institution and punishment for extra pair mating (EPM) or adultery is common. However, similar to other species with bi-parental care, both males and females frequently indulge in EPM in secrecy since it confers certain gender specific genetic benefits. Stability of faithful monogamy is therefore a conundrum. We model human mating system using game theory framework to study the effects of factors that can stabilize or destabilize faithful committed monogamy.ResultsAlthough mate guarding can partly protect the genetic interests, we show that it does not ensure monogamy. Social policing enabled by gossiping is another line of defense against adultery unique to humans. However, social policing has a small but positive cost to an individual and therefore is prone to free riding. We suggest that since exposure of adultery can invite severe punishment, the policing individuals can blackmail opportunistically whenever the circumstances permit. If the maximum probabilistic benefit of blackmailing is greater than the cost of policing, policing becomes a non-altruistic act and stabilizes in the society. We show that this dynamics leads to the coexistence of different strategies in oscillations, with obligate monogamy maintained at a high level. Deletion of blackmailing benefit from the model leads to the complete disappearance of obligate monogamy.ConclusionsObligate monogamy can be maintained in the population in spite of the advantages of EPM. Blackmailing, which makes policing a non-altruistic act, is crucial for the maintenance of faithful monogamy. Although biparental care, EPM, mate guarding and punishment are shared by many species, gossiping and blackmailing make the human mating system unique.

Background: The ecological role of actinomycetes and their secondary metabolites is not yet completely understood. Hypothesis: Actinomycetes and Streptomyces sp. in particular, are non-obligate predators of bacteria in soil. Evidence: Ability to grow on live bacterial cells as a sole source of nutrients. Prey cell lysis accompanying growth. Circumstantial evidence for the involvement of antimicrobials along with enzymes.Implications: This finding may open up a new source of novel secondary metabolites from the genus.