Posttranscriptional Modification to Modulate Progenitor Differentiation on Heterotypic Spheroids.

Cell aggregates are widely used to study heterotypic cellular interactions during the development of vascularization in vitro. In this study, we examined heterotypic cellular spheroids made of adipose-derived stem cells and CD34+/CD31- endothelial progenitor cells induced by the transfection of miR-148b mimic for de novo induction of osteogenic differentiation and miR-210 mimic for de novo induction of endotheliogenesis, respectively. The effect of the microRNA (miRs) mimic treatment group and induction time on codifferentiation was assessed in spheroids formed of transfected cells over the course of a 4-week culture. Based on gene and protein markers of osteogenic and endotheliogenic differentiation, as well as mineralization assays, our results showed that miRs directed cell differentiation and that progenitor maturity influenced the development of heterotypic cellular regions in aggregates. Overall, the success of coculture to create a prevascularized bone model is dependent on a number of factors, particularly the induction time of differentiation before combining the multiple cell types in aggregates. The approach that has been proposed could be valuable in creating vascularized bone tissue by employing spheroids as the building blocks of more complex issues through the use of cutting-edge methods such as 3D bioprinting.

Development of a multigenomic liquid biopsy (PROSTest) for prostate cancer in whole blood.

INTRODUCTION: We describe the development of a molecular assay from publicly available tumor tissue mRNA databases using machine learning and present preliminary evidence of functionality as a diagnostic and monitoring tool for prostate cancer (PCa) in whole blood. MATERIALS AND METHODS: We assessed 1055 PCas (public microarray data sets) to identify putative mRNA biomarkers. Specificity was confirmed against 32 different solid and hematological cancers from The Cancer Genome Atlas (n = 10,990). This defined a 27-gene panel which was validated by qPCR in 50 histologically confirmed PCa surgical specimens and matched blood. An ensemble classifier (Random Forest, Support Vector Machines, XGBoost) was trained in age-matched PCas (n = 294), and in 72 controls and 64 BPH. Classifier performance was validated in two independent sets (n = 263 PCas; n = 99 controls). We assessed the panel as a postoperative disease monitor in a radical prostatectomy cohort (RPC: n = 47). RESULTS: A PCa-specific 27-gene panel was identified. Matched blood and tumor gene expression levels were concordant (r = 0.72, p < 0.0001). The ensemble classifier ("PROSTest") was scaled 0%-100% and the industry-standard operating point of ≥50% used to define a PCa. Using this, the PROSTest exhibited an 85% sensitivity and 95% specificity for PCa versus controls. In two independent sets, the metrics were 92%-95% sensitivity and 100% specificity. In the RPCs (n = 47), PROSTest scores decreased from 72% ± 7% to 33% ± 16% (p < 0.0001, Mann-Whitney test). PROSTest was 26% ± 8% in 37 with normal postoperative PSA levels (<0.1 ng/mL). In 10 with elevated postoperative PSA, PROSTest was 60% ± 4%. CONCLUSION: A 27-gene whole blood signature for PCa is concordant with tissue mRNA levels. Measuring blood expression provides a minimally invasive genomic tool that may facilitate prostate cancer management.

Vascular persistence following precision micropuncture.

OBJECTIVE: The success of engineered tissues continues to be limited by time to vascularization and perfusion. Recently, we described a simple microsurgical approach, termed micropuncture (MP), which could be used to rapidly vascularize an adjacently placed scaffold from the recipient macrovasculature. Here we studied the long-term persistence of the MP-induced microvasculature. METHODS: Segmental 60 µm diameter MPs were created in the recipient rat femoral artery and vein followed by coverage with a simple Type 1 collagen scaffold. The recipient vasculature and scaffold were then wrapped en bloc with a silicone sheet to isolate intrinsic vascularization. Scaffolds were harvested at 28 days post-implantation for detailed analysis, including using a novel artificial intelligence (AI) approach. RESULTS: MP scaffolds demonstrated a sustained increase of vascular density compared to internal non-MP control scaffolds (p < 0.05) secondary to increases in both vessel diameters (p < 0.05) and branch counts (p < 0.05). MP scaffolds also demonstrated statistically significant increases in red blood cell (RBC) perfused lumens. CONCLUSIONS: This study further highlights that the intrinsic MP-induced vasculature continues to persist long-term. Its combination of rapid and stable angiogenesis represents a novel surgical platform for engineered scaffold and graft perfusion.

Accelerating Patterned Vascularization Using Granular Hydrogel Scaffolds and Surgical Micropuncture.

Bulk hydrogel scaffolds are common in reconstructive surgery. They allow for the staged repair of soft tissue loss by providing a base for revascularization. Unfortunately, they are limited by both slow and random vascularization, which may manifest as treatment failure or suboptimal repair. Rapidly inducing patterned vascularization within biomaterials has profound translational implications for current clinical treatment paradigms and the scaleup of regenerative engineering platforms. To address this long-standing challenge, a novel microsurgical approach and granular hydrogel scaffold (GHS) technology are co-developed to hasten and pattern microvascular network formation. In surgical micropuncture (MP), targeted recipient blood vessels are perforated using a microneedle to accelerate cell extravasation and angiogenic outgrowth. By combining MP with an adjacent GHS with precisely tailored void space architecture, microvascular pattern formation as assessed by density, diameter, length, and intercapillary distance is rapidly guided. This work opens new translational opportunities for microvascular engineering, advancing reconstructive surgery, and regenerative medicine.

Non-communicable diseases and their impact on depression, anxiety, and stress among the geriatric population residing in old age homes in Chennai, Tamil Nadu.

Background: Non-communicable diseases (NCDs) are most prevalent among the elderly population. Mental illness and chronic disease conditions are of utmost significance when considering their implications on various aspects such as well-being, quality of life, cost of treatment, and longevity of the affected individuals. There is a paucity of data from India to assess the prevalence of NCDs and their relation to depression, anxiety, and stress among the elderly population. Aim: The present study aims to determine the prevalence of NCDs and their relationship with depression, anxiety, and stress (DASS) among the geriatric population that resides in senior citizen homes (Old age homes) in Chennai. Materials and Methods: A cross-sectional study was conducted among the elderly population in old age homes located in Chennai. The research was carried out through offline methods during the period of January 2023 to April 2023. A total of 311 participants were involved in this study who were aged 60 and older. DASS 21 was used to study depression, anxiety, and stress. Results: The overall prevalence of depression was 84.2%, anxiety was 49.2%, and stress was 55.9% among the study participants. The findings of the study show that there is a statistically significant association, the odds of diabetes were 2 times higher (OR- 2.082, 95% CI: 1.225-3.888), the presence of hypertension was nearly 4.1 times higher (OR- 4.116, 95% CI: 2.110-8.030) and the odds of the presence of visual impairment were nearly 1.8 times higher (OR-1.810, 95% CI: 0.976-3.357) in developing the symptoms of depression. Conclusion: Screening of non-communicable diseases (NCDs) such as hypertension, diabetes, etc. for DASS among the elderly population is recommended at regular intervals, as elderly people are considered to be the most vulnerable age group population, worldwide.

Role of Reflux Symptom Index and Reflux Finding Score in Diagnosing Laryngopharyngeal Reflux: A Prospective Study.

Laryngopharyngeal Reflux Disease (LPRD) is caused due to reflux of gastric content into the larynx and pharynx. The present study was done to assess the role of Reflux Symptom Index (RSI) and Reflux Finding Score (RFS) in the treatment outcomes in symptomatic patients with LPRD. This is a prospective analytical study conducted on 200 patients for a period of 2 years, from January 2020 to February 2022. Patients suspected with LPR were evaluated using RSI and RFS, and both pre and post treatment scores were compared to assess the change in scores of RSI and RFS following 8 weeks of treatment with PPI (Proton pump inhibitor). The patients experienced a greater incidence of moderate symptoms in RSI. Wilcoxon signed-rank test showed significant difference between pre and post treatment scores with respect to reflux symptoms and reflux findings (p < 0.05). Implementation of RSI and RFS scoring system helped for early diagnosis of LPR, and a significant difference was seen between pre and post treatment scores in both RSI and RFS.

Physico-chemical and tribological properties of commercial oil - bio-lubricant mixtures dispersed with graphene nanoplatelets.

This study focuses on the physicochemical and tribological properties of bio-lubricants and commercial lubricant blends dispersed with graphene nanoplatelets. In the processing of the bio lubricant, special care was taken to ensure that the physicochemical properties do not deteriorate too much when the bio lubricant is blended with commercial oil. Calophyllum inophyllum (Tamanu tree) seed oil was used to prepare a penta-erythritol (PE) ester. The PE ester was mixed with commercial SN motor oil at 10, 20, 30 & 40% v/v concentrations. The oil samples are tested on a four-ball wear tester to see how well they perform under wear, friction, and extreme pressure conditions. The optimum blend of PE ester - commercial SN motor oil for the best performance is found in the first phase. Later the optimum blend of commercial oil and bio-lubricant is dispersed with graphene nanoplatelets in 0.025%, 0.05%, 0.1%, 0.25%, 0.5% and 1% weight fractions. A blend ratio of 30% bio-lubricant in commercial oil dispersed with 0.05% graphene nanoplatelets dramatically reduces friction and wear. During the extreme pressure test, commercial oil, and bio-lubricant blends performed better in load-carrying capacity and welding force, indicating an improved load-wear index. These improved properties due to the dispersion of graphene nanoplatelets could facilitate the use of a higher blend percentage of bio lubricant. Analysis of the worn surfaces after the EP test showed that bio lubricant, additives, and graphene worked together in the blend of bio lubricant and commercial oil.

AATF inhibition exerts antiangiogenic effects against human hepatocellular carcinoma.

Background and aims: Angiogenesis is a key factor in the growth and metastasis of hepatic tumors and thus a potential therapeutic target in hepatocellular carcinoma (HCC). In this study, we aim to identify the key role of apoptosis antagonizing transcription factor (AATF) in tumor angiogenesis and its underlying mechanisms in HCC. Methods: HCC tissues were analyzed for AATF expression by qRT-PCR and immunohistochemistry. Stable clones of control and AATF knockdown (KD) were established in human HCC cells. The effect of AATF inhibition on the angiogenic processes was determined by proliferation, invasion, migration, chick chorioallantoic membrane (CAM) assay, zymography, and immunoblotting techniques. Results: We identified high levels of AATF in human HCC tissues compared to adjacent normal liver tissues, and the expression was found to be correlated with the stages and tumor grades of HCC. Inhibiting AATF in QGY-7703 cells resulted in higher levels of pigment epithelium-derived factor (PEDF) than controls due to decreased matric metalloproteinase activity. Conditioned media from AATF KD cells inhibited the proliferation, migration, and invasion of human umbilical vein endothelial cells as well as the vascularization of the chick chorioallantoic membrane. Furthermore, the VEGF-mediated downstream signaling pathway responsible for endothelial cell survival and vascular permeability, cell proliferation, and migration favoring angiogenesis was suppressed by AATF inhibition. Notably, PEDF inhibition effectively reversed the anti-angiogenic effect of AATF KD. Conclusion: Our study reports the first evidence that the therapeutic strategy based on the inhibition of AATF to disrupt tumor angiogenesis may serve as a promising approach for HCC treatment.

Determination and comparison of antimicrobial activity of aqueous and ethanolic extracts of Amorphophallus paeoniifolius on periodontal pathogens: An in vitro study.

Background: People globally are turning to herbal products to reconnect with nature. Cost efficacy and minimal side effects are the reasons for this changeover. This study assessed the effect of Amorphophallus paeoniifolius as an antimicrobial agent against Porphyromonas gingivalis, Prevotella intermedia, and Fusobacterium nucleatum. Aim: To determine and compare the antimicrobial activity of aqueous and ethanolic extracts of A. paeoniifolius on periodontal pathogens. Materials and Methods: Aqueous and ethanolic extracts of A. paeoniifolius were tested against the standard strains of the selected bacteria. Minimum inhibitory concentrations (MIC) and minimum bactericidal concentration (MBC) were used. These tests assessed the lowest concentrations of test agent, either by showing a lack of turbidity or by no or few bacterial growth colonies, respectively. In this study, tetracycline hydrochloride was used as the control group. Results: Aqueous and ethanolic extracts of A. paeoniifolius showed antibacterial activity at various concentrations against the selected organisms. While assessing the MBC, the aqueous and ethanolic extracts of A. paeoniifolius and tetracycline hydrochloride exhibited bactericidal activity against F. nucleatum at all concentrations. The ethanolic extract of Amorphophallus paeoniifolius and tetracycline hydrochloride showed bactericidal action, whereas the aqueous extract exhibited bacteriostatic action against P. gingivalis. The aqueous and ethanolic extracts of A. paeoniifolius showed bacteriostatic action, whereas tetracycline hydrochloride showed bactericidal action against P. intermedia. Conclusion: Both aqueous and ethanolic extracts of A. paeoniifolius showed antibacterial activity against standard strains of P. gingivalis, P. intermedia, and F. nucleatum. The ethanolic extract showed a significant antibacterial effect against the selected microorganisms when compared to the aqueous extract of A. paeoniifolius.

Multi-dimensional data transmission using inverse-designed silicon photonics and microcombs.

The use of optical interconnects has burgeoned as a promising technology that can address the limits of data transfer for future high-performance silicon chips. Recent pushes to enhance optical communication have focused on developing wavelength-division multiplexing technology, and new dimensions of data transfer will be paramount to fulfill the ever-growing need for speed. Here we demonstrate an integrated multi-dimensional communication scheme that combines wavelength- and mode- multiplexing on a silicon photonic circuit. Using foundry-compatible photonic inverse design and spectrally flattened microcombs, we demonstrate a 1.12-Tb/s natively error-free data transmission throughout a silicon nanophotonic waveguide. Furthermore, we implement inverse-designed surface-normal couplers to enable multimode optical transmission between separate silicon chips throughout a multimode-matched fibre. All the inverse-designed devices comply with the process design rules for standard silicon photonic foundries. Our approach is inherently scalable to a multiplicative enhancement over the state of the art silicon photonic transmitters.

Mesenchymal Stem Cell-Derived Extracellular Vesicles for Therapeutic Use and in Bioengineering Applications.

Extracellular vesicles (EVs) are small lipid bilayer-delimited particles that are naturally released from cells into body fluids, and therefore can travel and convey regulatory functions in the distal parts of the body. EVs can transmit paracrine signaling by carrying over cytokines, chemokines, growth factors, interleukins (ILs), transcription factors, and nucleic acids such as DNA, mRNAs, microRNAs, piRNAs, lncRNAs, sn/snoRNAs, mtRNAs and circRNAs; these EVs travel to predecided destinations to perform their functions. While mesenchymal stem cells (MSCs) have been shown to improve healing and facilitate treatments of various diseases, the allogenic use of these cells is often accompanied by serious adverse effects after transplantation. MSC-produced EVs are less immunogenic and can serve as an alternative to cellular therapies by transmitting signaling or delivering biomaterials to diseased areas of the body. This review article is focused on understanding the properties of EVs derived from different types of MSCs and MSC-EV-based therapeutic options. The potential of modern technologies such as 3D bioprinting to advance EV-based therapies is also discussed.

Global assessment of spatiotemporal variability of wet, normal and dry conditions using multiscale entropy-based approach.

In recent decades, human-induced climate change has caused a worldwide increase in the frequency/intensity/duration of extreme events, resulting in enormous disruptions to life and property. Hence, a comprehensive understanding of global-scale spatiotemporal trends and variability of extreme events at different intensity levels (e.g., moderate/severe/extreme) and durations (e.g., short-term/long-term) of normal, dry and wet conditions is essential in predicting/forecasting/mitigating future extreme events. This article analyses these aspects using estimates of a non-stationary standardized precipitation evapotranspiration index corresponding to different accumulation periods for 0.5° resolution CRU grids at globe-scale. Results are analyzed with respect to changes in land-use/landcover and geographic/location indicators (latitude, longitude, elevation) at different time scales (decadal/annual/seasonal/monthly) for each continent. The analysis showed an (i) increasing trend in the frequency/count of both dry and wet conditions and variability of dry conditions, and (ii) contrasting (decreasing) trend in the variability of wet conditions, possibly due to climate change-induced variations in atmospheric circulations. Globally, the highest variability in the wet and dry conditions is found during the Northern hemisphere's winter season. The decadal-scale analysis showed that change in variability in dry and wet conditions has been predominant since the 1930s and 1950s, respectively and is found to be increasing in recent decades.

First Clinical Results of Fluorescence Lifetime-enhanced Tumor Imaging Using Receptor-targeted Fluorescent Probes.

PURPOSE: Fluorescence molecular imaging, using cancer-targeted near infrared (NIR) fluorescent probes, offers the promise of accurate tumor delineation during surgeries and the detection of cancer specific molecular expression in vivo. However, nonspecific probe accumulation in normal tissue results in poor tumor fluorescence contrast, precluding widespread clinical adoption of novel imaging agents. Here we present the first clinical evidence that fluorescence lifetime (FLT) imaging can provide tumor specificity at the cellular level in patients systemically injected with panitumumab-IRDye800CW, an EGFR-targeted NIR fluorescent probe. EXPERIMENTAL DESIGN: We performed wide-field and microscopic FLT imaging of resection specimens from patients injected with panitumumab-IRDye800CW under an FDA directed clinical trial. RESULTS: We show that the FLT within EGFR-overexpressing cancer cells is significantly longer than the FLT of normal tissue, providing high sensitivity (>98%) and specificity (>98%) for tumor versus normal tissue classification, despite the presence of significant nonspecific probe accumulation. We further show microscopic evidence that the mean tissue FLT is spatially correlated (r > 0.85) with tumor-specific EGFR expression in tissue and is consistent across multiple patients. These tumor cell-specific FLT changes can be detected through thick biological tissue, allowing highly specific tumor detection and noninvasive monitoring of tumor EFGR expression in vivo. CONCLUSIONS: Our data indicate that FLT imaging is a promising approach for enhancing tumor contrast using an antibody-targeted NIR probe with a proven safety profile in humans, suggesting a strong potential for clinical applications in image guided surgery, cancer diagnostics, and staging.

Regenerative Engineering: Current Applications and Future Perspectives.

Many pathologies, congenital defects, and traumatic injuries are untreatable by conventional pharmacologic or surgical interventions. Regenerative engineering represents an ever-growing interdisciplinary field aimed at creating biological replacements for injured tissues and dysfunctional organs. The need for bioengineered replacement parts is ubiquitous among all surgical disciplines. However, to date, clinical translation has been limited to thin, small, and/or acellular structures. Development of thicker tissues continues to be limited by vascularization and other impediments. Nevertheless, currently available materials, methods, and technologies serve as robust platforms for more complex tissue fabrication in the future. This review article highlights the current methodologies, clinical achievements, tenacious barriers, and future perspectives of regenerative engineering.

Efficacy and Safety of Acotiamide Versus Mosapride in Patients With Functional Dyspepsia Associated With Meal-Induced Postprandial Distress Syndrome: A Phase III Randomized Clinical Trial.

BACKGROUND:  Acotiamide is a novel prokinetic drug that acts by enhancing the release of acetylcholine and is used in the treatment of functional dyspepsia-postprandial distress syndrome (FD-PDS). Mosapride is indicated to FD-PDS as per the Rome III treatment guidelines. Mosapride 5 mg three times daily (TID) is approved by the Drugs Controller General of India (DCGI) for the treatment of FD-PDS. The objective of this study was to determine the efficacy and safety of Acotiamide in comparison with Mosapride on FD-PDS. METHODS: The 220 patients of either gender (aged 18-64 years) with active PDS included in the study were centrally randomized 1:1 to receive either 100 mg Acotiamide (test product) or 5 mg Mosapride (reference product) TID for four weeks. Responder rates for the overall treatment effect (OTE) at the end of four weeks were the primary efficacy endpoint. Secondary efficacy endpoints included the elimination rate of postprandial fullness, upper abdominal bloating, and early satiation. The study also evaluated the OTE at each week, individual symptom scores, and quality of life (QoL) assessed by the Short Form-Nepean Dyspepsia Index questionnaire (SF-NDI). The safety endpoints included assessments of treatment-emergent adverse events (TEAEs). RESULTS:  At the end of four weeks, the responders in the Acotiamide versus Mosapride group for OTE was 98% versus 93.27% in the per-protocol (PP) population. Among the intent to treat (ITT) population, the comparison of Acotiamide versus Mosapride stood at 95.15% versus 89.81%. Secondary efficacy endpoints were significantly improved with 100 mg TID Acotiamide, which was evident from the improvement in postprandial fullness (14.56%), upper abdominal bloating (15.53%), early satiation (10.68%), and QoL (13.7 ± 4.67). CONCLUSIONS:  Our study results demonstrated that Acotiamide is effective, safe, and well-tolerated and had significantly improved the QoL over a four-week treatment period in FD-PDS patients. The efficacy and safety profiles of Acotiamide were similar to Mosapride.

Navigating the Genomic Landscape of Human Adipose Stem Cell-Derived ß-Cells.

Diabetes is a pandemic manifested through glucose dysregulation mediated by inadequate insulin secretion by beta cells. A beta cell replacement strategy would transform the treatment paradigm from pharmacologic glucose modulation to a genuine cure. Stem cells have emerged as a potential source for beta cell (ß-cell) engineering. The detailed generation of functional ß-cells from both embryonic and induced pluripotent stem cells has recently been described. Adult stem cells, including adipose derived, may also offer a therapeutic approach, but remain ill defined. In our study, we performed an in-depth assessment of insulin-producing beta cells generated from human adipose, irrespective of donor patient age, gender, and health status. Cellular transformation was confirmed using flow cytometry and single-cell imaging. Insulin secretion was observed with glucose stimulation and abrogated following palmitate exposure, a common free fatty acid implicated in human beta cell dysfunction. We used next-generation sequencing to explore gene expression changes before and after differentiation of patient-matched samples, which revealed more than 5,000 genes enriched. Adipose-derived beta cells displayed comparable gene expression to native ß-cells. Pathway analysis demonstrated relevance to stem cell differentiation and pancreatic developmental processes, which are vital to cellular function, structural development, and regulation. We conclude that the functions associated with adipose derived beta cells are mediated through relevant changes in the transcriptome, which resemble those seen in native ß-cell morphogenesis and maturation. Therefore, they may represent a viable option for the clinical translation of stem cell-based therapies in diabetes.

Essential role of the histone lysine demethylase KDM4A in the biology of malignant pleural mesothelioma (MPM).

BACKGROUND: Malignant pleural mesothelioma (MPM) is a highly aggressive cancer with a dismal prognosis. There is increasing interest in targeting chromatin regulatory pathways in difficult-to-treat cancers. In preliminary studies, we found that KDM4A (lysine-specific histone demethylase 4) was overexpressed in MPM. METHODS: KDM4A protein expression was determined by immunohistochemistry or immunoblotting. Functional inhibition of KDM4A by targeted knockdown and small molecule drugs was correlated to cell growth using cell lines and a xenograft mouse model. Gene expression profiling was performed to identify KDM4A-dependent signature pathways. RESULTS: Levels of KDM4A were found to be significantly elevated in MPM patients compared to normal mesothelial tissue. Inhibiting the enzyme activity efficiently reduced cell growth in vitro and reduced tumour growth in vivo. KDM4A inhibitor-induced apoptosis was further enhanced by the BH3 mimetic navitoclax. KDM4A expression was associated with pathways involved in cell growth and DNA repair. Interestingly, inhibitors of the DNA damage and replication checkpoint regulators CHK1 (prexasertib) and WEE1 (adavosertib) within the DNA double-strand break repair pathway, cooperated in the inhibition of cell growth. CONCLUSIONS: The results establish a novel and essential role for KDM4A in growth in preclinical models of MPM and identify potential therapeutic approaches to target KDM4A-dependent vulnerabilities.

Antibody Therapy: From Diphtheria to Cancer, COVID-19, and Beyond.

The dawn of the 20th century saw the formative years of developments in immunology. In particular, immunochemistry, specifically pertaining to antibodies, was extensively studied. These studies laid the foundations for employing antibodies in a variety of ways. Not surprisingly, antibodies have been used for applications ranging from biomedical research to disease diagnostics and therapeutics to evaluation of immune responses during natural infection and those elicited by vaccines. Despite recent advancements in cellular immunology and the excitement of T cell therapy, use of antibodies represents a large proportion of immunotherapeutic approaches as well as clinical interventions. Polyclonal antibodies in the form of plasma or sera continue to be used to treat a number of diseases, including autoimmune disorders, cancers, and infectious diseases. Historically, antisera to toxins have been the longest serving biotherapeutics. In addition, intravenous immunoglobulins (IVIg) have been extensively used to treat not only immunodeficiency conditions but also autoimmune disorders. Beyond the simplistic suppositions of their action, the IVIg have also unraveled the immune regulatory and homeostatic ramifications of their use. The advent of monoclonal antibodies (MAbs), on the other hand, has provided a clear pathway for their development as drug molecules. MAbs have found a clear place in the treatment of cancers and extending lives and have been used in a variety of other conditions. In this review, we capture the important developments in the therapeutic applications of antibodies to alleviate disease, with a focus on some of the recent developments.

Th1 skewed immune response of whole virion inactivated SARS CoV 2 vaccine and its safety evaluation.

We report the development and evaluation of safety and immunogenicity of a whole virion inactivated (WVI) SARS-CoV-2 vaccine (BBV152), adjuvanted with aluminum hydroxide gel (Algel), or TLR7/8 agonist chemisorbed Algel. We used a well-characterized SARS-CoV-2 strain and an established Vero cell platform to produce large-scale GMP-grade highly purified inactivated antigen. Product development and manufacturing process were carried out in a BSL-3 facility. Immunogenicity and safety were determined at two antigen concentrations (3µg and 6µg), with two different adjuvants, in mice, rats, and rabbits. Our results show that BBV152 vaccine formulations generated significantly high antigen-binding and neutralizing antibody titers (NAb), at both concentrations, in all three species with excellent safety profiles. The inactivated vaccine formulation contains TLR7/8 agonist adjuvant-induced Th1-biased antibody responses with elevated IgG2a/IgG1 ratio and increased levels of SARS-CoV-2-specific IFN-γ+ CD4+ T lymphocyte response. Our results support further development for phase I/II clinical trials in humans.