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Skeletal disabilities are a prominent burden on the present population with an increasing life span. Advances in osteopathy have provided various medical support for bone-related diseases, including pharmacological and prosthesis interventions. However, therapeutics and post-surgery complications are often reported due to side effects associated with modern-day therapies. Thus, therapies utilizing natural means with fewer toxic or other side effects are the key to acceptable interventions. Flavonoids constitute a class of bioactive compounds found in dietary supplements, and their pharmacological attributes have been well appreciated. Recently, flavonoids' role is gaining renowned interest for its effect on bone remodeling. A wide range of flavonoids has been found to play a pivotal role in the major bone signaling pathways, such as wingless-related integration site (Wnt)/β-catenin, bone morphogenetic protein (BMP)/transforming growth factor (TGF)-β, mitogen-activated protein kinase (MAPK), etc. However, the reduced bioavailability and the absorption of flavonoids are the major limitations inhibiting their use against bone-related complications. Recent utilization of nanotechnological approaches and other delivery methods (biomaterial scaffolds, micelles) to target and control release can enhance the absorption and bioavailability of flavonoids. Thus, we have tried to recapitulate the understanding of the role of flavonoids in regulating signaling mechanisms affecting bone remodeling and various delivery methods utilized to enhance their therapeutical potential in treating bone loss. [ABSTRACT FROM AUTHOR]

The progression of the COVID-19 pandemic has generated numerous emerging variants of SARS-CoV-2 on a global scale. These variants have gained evolutionary advantages, comprising high virulence and serious infectivity due to multiple spike glycoprotein mutations. As a reason, variants are demonstrating significant abilities to escape the immune responses of the host. The D614G mutation in the S-glycoprotein of SARS-CoV-2 variants has shown the most efficient interaction with the ACE2 receptor of the cells. This explicit mutation at amino acid position 614 (aspartic acid-to-glycine substitution) is the prime cause of infection and re-infection. It changes the conformation of RBD and cleavage patterns S-glycoprotein with higher stability, replication fitness, and fusion efficiencies. Therefore, this review aims to provide several crucial pieces of information associated with the D614 mutational occurrence of SARS-CoV-2 variants and their infectivity patterns. This review will also effectively emphasize the mechanism of action of D614G mutant variants, immune escape, and partial vaccine escape of this virus. Furthermore, the viral characteristic changes leading to the current global pandemic condition have been highlighted. Here, we have tried to illustrate a novel direction for future researchers to develop effective therapeutic approaches and counterweight strategies to minimize the spread of COVID-19. Key points • D614G mutation arises within the S-glycoprotein of significant SARS-CoV-2 variants. • The D614G mutation affects infection, re-infection, cleavage patterns of S-glycoprotein, and replication fitness of SARS-CoV-2 variants. • The D614G mutation influences the immunity and partial vaccine escape. [ABSTRACT FROM AUTHOR]

The Ebola virus disease is a deadly pathogenic disease caused by the Ebola virus. It has been observed that this disease causes a high case-fatality rate. Several species of this virus were detected from the genus Ebola virus. Among them, four species of this virus (Ebola, Taï Forest, Sudan, and Bundibugyo) caused disease in humans. Scientists are now focusing on the various therapeutic developments for the treatment of this disease. This article has attempted to depict the development of the entire therapeutic scenario of this disease. In addition, the article tried to illustrate the developmental strategy of the different therapeutics such as small-molecule inhibitors, small interfering RNAs, antibodies, ion channel inhibitors, interferons, and combination therapy against Ebola virus disease. Presently, two monoclonal antibodies (REGN-EB3 and mAb114) showed better efficacy in the Pamoja tuLinde Maisha trial and received approval from the United States Food and Drug Administration. However, scientists should focus on developing more economic therapeutics. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a degenerative disease of the joints and is one of the leading causes of disability in adults. However, there are no key therapeutics for OA and medical treatment is based on managing the symptoms and slowing down progression of the disease. Diagnostics based on clinical examination and radiography have provided little information about metabolic changes in joint tissues, disease onset and progression. Due to lack of effective methods for early detection and evaluation of treatment outcome, the measurement of biochemical markers (biomarkers) shows promise as a prospective method aiding in disease monitoring. OA biomarkers that are present in biological fluids such as blood, urine and synovial fluid, sources that are easily isolated from body, are of particular interest. Moreover, there are increasingly more studies identifying and developing new biomarkers for OA. In this review, efforts have been made to summarize the biomarkers that have been reported in recent studies on patients. We also tried to classify biomarkers according to tissue metabolism (bone, cartilage and synovial metabolism markers), pathological pathways (inflammatory and genetic markers) and biological function (chemokines, growth factors, acute phase proteins, etc.). [ABSTRACT FROM AUTHOR]

Purpose: To overcome the therapeutic restrictions offered by hydrophobic quercetin (Qu), this study aims to synthesize MPEG-PLA encapsulated Qu nanoparticle and to evaluate their anticancer efficacy. Materials and Methods: In vitro anticancer potential and apoptotic studies were done by cell cytotoxicity assay and flow cytometry, respectively . MPEG-PLA-Qu nanoparticles were evaluated for anticancer efficacy in vivo using xenograft mice model. TUNEL assay was performed to observe the frequency of apoptotic cells in vivo. Results: The hydrodynamic particle size, polydispersity index, zeta potential and drug loading % of MPEG-PLA-Qu nanoparticle was 155.3 ± 3.2 nm, 0.2 ± 0.05, −3.14 mV and 5.3 ± 1.1%, respectively. Also, MPEG-PLA-Qu showed sustained drug release for 10 days. In vitro results showed that MPEG-PLA-Qu could efficiently induce apoptosis in triple negative breast cancer cell line (MDA-MB-231) with higher amount of quercetin in cell lysate treated with MPEG-PLA-Qu in comparison to free quercetin. In xenograft model for breast cancer, peritumorally injected MPEG-PLA-Qu significantly inhibited the tumor growth. Moreover, TUNEL assay showed more occurrence of apoptotic cells in MPEG-PLA-Qu treated tumors compared to free quercetin at similar dose. Conclusion: Our data suggest that MPEG-PLA-Qu nanoparticle can have a promising clinical potential for the treatment of breast cancer. [ABSTRACT FROM AUTHOR]

Some individuals with non-small-cell lung cancer (NSCLC) benefit from therapies targeting epidermal growth factor receptor (EGFR), and the characterization of a new mechanism of resistance to the EGFR-specific antibody gefitinib will provide valuable insight into how therapeutic strategies might be designed to overcome this particular resistance mechanism. The G719S and T790M mutations and their combination were involved in causing different conformational redistribution of EGFR. In the present computational study, we analyzed the impact and structural influence of G719S/T790M double mutation (DM) in EGFR with ligand (gefitinib) through molecular dynamic simulation (50 ns) and docking analysis. We observed the escalation in distance between the functional loop and activation loop with respect to T790M mutation compared to the G719S mutation. Furthermore, we confirmed that the G719S mutation causes the ligand to move closer to the hinge region, whereas T790M makes the ligand escape from the binding pocket. Obtained results provide with an explanation for the resistance induced by T790M and a vital clue for the design of drugs to combat gefitinib resistance. [ABSTRACT FROM AUTHOR]

Abstract: India''s biotechnology industry has been growing towards new heights in conjunction with the recent economic outburst. The country has the potential to revolutionize biopharmaceutical and healthcare sectors. In this review, we have highlighted the achievements of India''s biotechnology industry, especially biopharmaceutical and healthcare sectors that include therapeutics, diagnostics, stem cell research, human healthcare related bioinformatics and animal health care. We have also described regulatory mechanisms involved in India''s health care biotech including manpower development. [Copyright &y& Elsevier]

The transdermal drug delivery system is an exceptionally safe and well-tolerable therapeutic approach that has immense potential for delivering active components against bone-related pathologies. However, its use is limited in the current clinical practices due to the low skin permeability of most active drugs in the formulation. Thus, innovations in the methodologies of skin permeation enhancement techniques are suggested to overcome this limitation. Although various transdermal drug delivery systems are studied to date, there are insufficient studies comparing the therapeutic efficacy of transdermal delivery systems to oral delivery systems. Thus, creating a decision-making dilemma between oral or transdermal therapies. Therefore, a timely review is inevitable to develop a platform for future researchers to develop next-generation transdermal drug delivery strategies against skeletal diseases that must be convenient and cost-effective for the patients with improved therapeutic efficacy. Here, we will outline the most recent strategies that can overcome the choice limitation of the drug and enhance the transdermal adsorption of various types of drugs to treat bone disorders. For the first time, in this review paper, we will highlight the preclinical and clinical studies on the different transdermal delivery methods. Thus, providing insight into the current therapeutic approaches and suggesting new directions for the advancements in transdermal drug delivery systems against bone disorders. [Display omitted] [ABSTRACT FROM AUTHOR]

COVID-19 is now pandemic throughout the world. Scientist, doctors are searching for effective therapy of this diseases. The remdesivir, an antiviral drug, is appeared as 'molecule of hope' for the treatment of this disease. USFDA gave emergency approval to this drug for the treatment of COVID-19. The molecular mechanism is unknown. In this paper, we tried to describe the probable molecular mechanism of remdesivir to inhibit the RNA synthesis of SARS-CoV-2. However, more detail mechanism is needed to understand mechanism of action of remdesivir. [ABSTRACT FROM AUTHOR]