Amelioration of endothelial integrity by 3,5,4'-trihydroxy-trans-stilbene against high-fat-diet-induced obesity and -associated vasculopathy and myocardial infarction in rats, targeting TLR4/MyD88/NF-κB/iNOS signaling cascade.

Exacerbated expression of TLR4 protein (foremost pattern recognition receptor) during obesity could trigger NF-κB/iNOS signaling through linker protein (MyD88), predisposed to an indispensable inflammatory response. The induction of this detrimental cascade leads to myocardial and vascular abnormalities. Molecular docking was studied for protein-ligand interaction between these potential targets and resveratrol. The pre-treatment of resveratrol (20 mg/kg/p.o/per day for ten weeks) was given to investigate the therapeutic effect against HFD-induced obesity and associated vascular endothelial dysfunction (VED) and myocardial infarction (MI) in Wistar rats. In addition to accessing the levels of serum biomarkers for VED and MI, oxidative stress, inflammatory cytokines, and histopathology of these tissues were investigated. Lipopolysaccharide (for receptor activation) and protein expression analysis were introduced to explore the mechanistic involvement of TLR4/MyD88/NF-κB/iNOS signaling. Assessment of in-silico analysis showed significant interaction between protein and ligand. The involvement of this proposed signaling (TLR4/MyD88/NF-κB/iNOS) was further endorsed by the impact of lipopolysaccharide and protein expression analysis in obese and treated rats. Moreover, resveratrol pre-treated rats showed significantly lowered cardio and vascular damage measured by the distinct down expression of the TLR4/MyD88/NF-κB/iNOS pathway by resveratrol treatment endorses its ameliorative effect against VED and MI.

Liposome functionalized reduced graphene oxide for rapid electrochemical sensing of bacteria.

Pathogenic bacteria represent a severe threat to global public health, particularly with the growing rate of antibiotic resistance, and, therefore, indicate a critical need for developing efficient sensing platforms. Liposome-based sensors are collocating interest due to their intrinsic fusogenic ability to fuse with the outer membrane of bacteria. However, the lack of a conducting property limits their applicability for developing biosensing platforms. In this study, we report conjugation of liposomes with reduced graphene oxide (rGO) for fabricating a rapid and sensitive biosensor for electrochemical detection of Escherichia coli (E. coli). The large surface area of rGO facilitated binding of liposomes with their surface, and the intrinsic electrical and biocompatible properties assisted electrochemical sensing of bacteria. The electrochemical response of the liposome and the rGO-liposome coated electrode shows nonconducting and conducting characteristics, respectively. A significant change in the peak current of differential pulse voltammetry with the gradual variation of bacterial density in the electrolyte was observed for the glassy carbon electrode rGO-liposome (GCE-L-rGO) surface only. The detection sensitivity of GCE-L-rGO sensors was ∼26 µA/106 cells per ml of electrolyte for varying cell densities from 3 × 103 to 3 × 104 cells/ml. The proposed sensing technique can serve as an alternative to conventional methodologies for rapid and in situ detection of bacterial load in different samples, laying the foundation for new applications in clinical diagnostics.

Privacy preserving data sharing method for social media platforms.

Digital security as a service is a crucial aspect as it deals with user privacy provision and secure content delivery to legitimate users. Most social media platforms utilize end-to-end encryption as a significant security feature. However, multimedia data transmission in group communication is not encrypted. One of the most important objectives for a service provider is to send the desired multimedia data/service to only legitimate subscriber. Broadcast encryption is the most appropriate cryptographic primitive solution for this problem. Therefore, this study devised a construction called anonymous revocable identity-based broadcast encryption that preserves the privacy of messages broadcasted and the identity of legitimate users, where even revoked users cannot extract information about the user's identity and sent data. The update key is broadcast periodically to non-revoked users, who can obtain the message using the update and decryption keys. A third-party can also revoke the users. It is proven that the proposed construction is semantically secure against IND-ID-CPA attacks and efficient in terms of computational cost and communication bandwidth.

Review of Shikonin and Derivatives: Isolation, Chemistry, Biosynthesis, Pharmacology and Toxicology.

Shikonin and its derivatives, isolated from traditional medicinal plant species of the genus Lithospermum, Alkanna, Arnebia, Anchusa, Onosma, and Echium belonging to the Boraginaceae family, have numerous applications in foods, cosmetics, and textiles. Shikonin, a potent bioactive red pigment, has been used in traditional medicinal systems to cure various ailments and is well known for its diverse pharmacological potential such as anticancer, antithrombotic, neuroprotective, antidiabetic, antiviral, anti-inflammatory, anti-gonadotropic, antioxidants, antimicrobial and insecticidal. Herein, updated research on the natural sources, pharmacology, toxicity studies, and various patents filed worldwide related to shikonin and approaches to shikonin's biogenic and chemical synthesis are reviewed. Furthermore, recent studies to establish reliable production systems to meet market demand, functional identification, and future clinical development of shikonin and its derivatives against various diseases are presented.

An Efficient and Secure Data Sharing Method Using Asymmetric Pairing with Shorter Ciphertext to Enable Rapid Learning in Healthcare.

The recent advent of cloud computing provides a flexible way to effectively share data among multiple users. Cloud computing and cryptographic primitives are changing the way of healthcare unprecedentedly by providing real-time data sharing cost-effectively. Sharing various data items from different users to multiple sets of legitimate subscribers in the cloud environment is a challenging issue. The online electronic healthcare system requires multiple data items to be shared by different users for various purposes. In the present scenario, COVID-19 data is sensitive and must be encrypted to ensure data privacy. Secure sharing of such information is crucial. The standard broadcast encryption system is inefficient for this purpose. Multichannel broadcast encryption is a mechanism that enables secure sharing of different messages to different set of users efficiently. We propose an efficient and secure data sharing method with shorter ciphertext in public key setting using asymmetric (Type-III) pairings. The Type-III setting is the most efficient form among all pairing types regarding operations required and security. The semantic security of this method is proven under decisional BDHE complexity assumption without random oracle model.

Ketoprofen-FA Co-crystal: In Vitro and In Vivo Investigation for the Solubility Enhancement of Drug by Design of Expert.

The present piece of research work is framed for improving the solubility of ketoprofen by forming co-crystal using fumaric acid as a coformer. Co-crystal of ketoprofen and fumaric acid was prepared by simple solvent-assisted grinding method, containing drug and coformer as independent variables and solubility and % drug release were assumed to be dependent variables. Differential scanning calorimetry, Fourier transform infrared spectroscopy, X-ray diffraction, nuclear magnetic resonance and scanning electron microscopy techniques were used to characterize the preparation of optimized batch of co-crystal and further, evaluated for in vitro and in vivo anti-inflammatory and analgesic activities. Based on results of solubility and dissolution rate studies the formulation showed magnified improvement in both the properties on co-crystallization. The values of Gibbs free energy are negative at all levels of carrier demonstrating spontaneity of the drug solubilization process. The IC50 value of optimized batch of co-crystal formulation and the pure drug was observed as 327.33 µg/ml and 556.11 µg/ml, respectively, demonstrating that co-crystal formulation possesses more percentage protection against protein denaturation than the drug ketoprofen. In vivo (anti-inflammatory and analgesic) activities revealed that optimized batch of co-crystal formulation delivered a rapid pharmacological response in Wistar rats and albino mice when compared with standard drug.

Synthesis and evaluation of antimicrobial, antitubercular and anticancer activities of 2-(1-benzoyl-1H-benzo[d]imidazol-2-ylthio)-N-substituted acetamides.

BACKGROUND: The study describes the synthesis, characterization, in vitro antimicrobial and anticancer evaluation of a series of 2-(1-benzoyl-1H-benzo[d]imidazol-2-ylthio)-N-substituted acetamide derivatives. The synthesized derivatives were also assessed for in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv. The compounds found active in in vitro study were assessed for their in vivo antitubercular activity in mice models and for their inhibitory action on vital mycobacterial enzymes viz, isocitrate lyase, pantothenate synthetase and chorismate mutase. RESULTS: Compounds 8, 9 and 11 emerged out as excellent antimicrobial agents in antimicrobial assays when compared to standard antibacterial and antifungal drugs. The results of anticancer activity displayed that majority of the derivatives were less cytotoxic than standard drugs (tamoxifen and 5-fluorouracil) towards MCF7 and HCT116 cell lines. However, compound 2 (IC50 = 0.0047 µM/ml) and compound 10 (IC50 = 0.0058 µM/ml) showed highest cytotoxicity against MCF7 and HCT116 cell lines, respectively. The results of in vivo antitubercular activity revealed that a dose of 1.34 mg/kg was found to be safe for the synthesized compounds. The toxic dose of the compounds was 5.67 mg/kg while lethal dose varied from 1.81 to 3.17 mg/kg body weight of the mice. Compound 18 inhibited all the three mycobacterial enzymes to the highest level in comparison to the other synthesized derivatives but showed lesser inhibition as compared to streptomycin sulphate. CONCLUSIONS: A further research on most active synthesized compounds as lead molecules may result in discovery of novel anticancer and antitubercular agents.

Synthesis, characterization, biological evaluation and molecular docking studies of 2-(1H-benzo[d]imidazol-2-ylthio)-N-(substituted 4-oxothiazolidin-3-yl) acetamides.

BACKGROUND: A series of 2-(1H-benzo[d]imidazol-2-ylthio)-N-(substituted 4-oxothiazolidin-3-yl) acetamides was synthesized and characterized by physicochemical and spectral means. The synthesized compounds were evaluated for their in vitro antimicrobial activity against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Candida albicans and Aspergillus niger by tube dilution method. The in vitro cytotoxicity study of the compounds was carried out against human colorectal (HCT116) cell line. The most promising anticancer derivatives (5l, 5k, 5i and 5p) were further docked to study their binding efficacy to the active site of the cyclin-dependent kinase-8. RESULTS: All the compounds possessed significant antimicrobial activity with MIC in the range of 0.007 and 0.061 µM/ml. The cytotoxicity study revealed that almost all the derivatives were potent in inhibiting the growth of HCT116 cell line in comparison to the standard drug 5-fluorouracil. Compounds 5l and 5k (IC50 = 0.00005 and 0.00012 µM/ml, respectively) were highly cytotoxic towards HCT116 cell line in comparison to 5-fluorouracil (IC50 = 0.00615 µM/ml) taken as standard drug. CONCLUSION: The molecular docking studies of potent anticancer compounds 5l, 5k, 5i and 5p showed their putative binding mode and significant interactions with cyclin-dependent kinase-8 as prospective agents for treating colon cancer.

Diazenyl Derivatives and their Complexes as Anticancer Agents.

In the past years, many diazenyl compounds (i.e diazenecarboxamides, diazeniumdiolate prodrugs, diazenyl complexes etc.) have been prepared for the evaluation of their cytotoxic potential towards various cancer cell lines. Majority of them have shown promising cytotoxic activities even against several drug resistant cell lines. These derivatives have shown their effect by acting as alkylating agents, releasers of cytotoxic NO, targeting receptors like tyrosine kinase, EGFR or targeting enzymes like GST, AGT, CDKs etc. Their interaction with different receptors or enzymes leads to DNA damage, necrosis or apoptosis resulting in cell death. The present review will cover updated information on the synthetic methodologies and cytotoxic potential of diazenyl derivatives developed during the past years along with the recent developments. This may prove to be helpful for the researchers to develop novel anticancer drugs in future by molecular modifications of potential derivatives with better cytotoxic activities.

Polymer Drug Conjugates: Recent Advancements in Various Diseases.

During the past decade, the arena of polymer therapeutics has acquired considerable interest and accompanied by advanced designs and chemical properties of polymer-drug conjugates. Various polymers, such as poly (ethylene glycol) (PEG), N-(2-hydroxypropyl) methacrylamide (HPMA), poly(glycolic acid) (PGA) and poly(lactide-co-glycolide) (PLGA) have been used successfully for clinical utilization from decades. These polymers are used in combination of drugs in such a manner that they target the specific tissues and thus the toxicity of drugs to other tissues is reduced. Presently, numerous polymer drug conjugates are under clinical trial for treatment of various diseases including cancer, diabetes, AIDS, rheumatoid arthritis etc. Many protein-polymer conjugates have been approved by FDA for clinical use but till date, no polymer-synthetic drug conjugate is approved by FDA, although many of them are undergoing final phase of clinical trials. This review highlights the recent advancements in the polymer-drug conjugates for treatment of various diseases and their preclinical and clinical status.

Perspectives of Benzimidazole Derivatives as Anticancer Agents in the New Era.

Cancer is one of the deadliest diseases nowadays and is a great topic for research as the challenging task is to develop new entities with selectivity towards cancerous cells. Heterocyclic compounds are of great importance in medicinal chemistry as they possess an extensive range of therapeutic applications. Benzimidazole is one such important heterocyclic organic compound having structural analogy to nucleotides found in human body and hence is an important pharmacophore in medicinal chemistry. A variety of marketed drugs containing benzimidazole are thiabendazole, flubendazole (anthelmintic), astmizole (antihistaminic), lansoprazole and omeprazole (antiulcerative). In the light of the above facts, this review is an attempt to summarize the collective contributions from the authors around the world in the field of anticancer agents. This review highlights synthetic schemes and anticancer activity results of the research done in the past years.

Diazenyl derivatives as therapeutic and diagnostic agents acting on central nervous system.

In last decade, the development of new drugs and drug products for central nervous system (CNS) has remained limited due to incomplete elucidation of pathophysiology of many CNS disorders, complexity of the diseases and the lack of technologies for delivery through the blood-brain barrier (BBB). In this article we will summarize the development of diazenyl derivatives of many biologically active moieties like benzodiazepine, formazan, indole, pyrimidine, thiazole, sulfonamide etc. as diagnostic and therapeutic agents for CNS. The potential of already existing azo compounds as potent CNS agents have also been discussed. This overview will provide the researchers an opportunity for further development of new diazenyl derivatives in CNS area.

4-[1-(Substituted aryl/alkyl carbonyl)-benzoimidazol-2-yl]-benzenesulfonic acids: synthesis, antimicrobial activity, QSAR studies, and antiviral evaluation.

A series of 4-[1-(substituted aryl/alkyl carbonyl)-benzoimidazol-2-yl]-benzene sulphonic acids (1-20) was synthesized and evaluated, in vitro, for their antimicrobial activity and the results indicated that compounds 4-[1-(4-Nitrobenzoyl)-1H-benzoimidazol-2-yl]-benzenesulfonic acid (9) and 4-(1-octadec-9-enoyl-1H-benzoimidazol-2-yl)-benzenesulfonic acid (18) were found to be the most active ones. QSAR investigations indicated that the multi-target QSAR model was effective in describing the antimicrobial activity over the one-target QSAR models. Further the mt-QSAR model indicated the importance of the topological parameter, Balaban index (J) followed by the electronic parameter, LUMO and topological parameter, valence second order molecular connectivity index (2χv) in describing the antimicrobial activity of synthesized compounds (1-20).