In silico approach helps develop biomedicines and is useful for exploring the pharmacology of potential therapeutics using computer-simulated models. In vitro assays were used to determine the anti-microbial and cytotoxic efficacies of silver nanoparticles (AgNPs) synthesized with the shrub Lycium shawii. In silico predicting was performed to assess the L. shawii metabolites identified using QTOF-LCMS for their pharmacological properties. L. shawii mediated AgNPs were synthesized and characterized (FTIR, TEM, SEM, DLS and EDX). The anti-bacterial efficacies of L. shawii extract, AgNPs, and penicillin-conjugated AgNPs (pen-AgNPs) were determined. The cytotoxicity of the AgNPs was measured against colorectal cancer cell line (HCT116), normal breast epithelium (MCF 10 A), and breast cancer cell line (MDA MB 231). Five molecules (costunolide, catechin, emodin, lyciumaside, and aloe emodin 11-O-rhamnoside) were detected in the L. shawii extract. AgNPs (69 nm) were spherical with crystallographic structure. All three agents prepared showed inhibitory activity against the tested bacteria, the most efficacious being pen-AgNPs. High cytotoxicity of AgNPs (IC₅₀ 62 μg/ml) was observed against HCT116, IC₅₀ was 78 μg/ml for MCF 10 A, and 250 μg/ml for MDA MB 231, of which cells showed apoptotic features under TEM examination. The in silico approach indicated that the carbonic anhydrase IX enzyme was the target molecule mediating anti-cancer and anti-bacterial activities and that emodin was the metabolite in action. Combining in vitro studies and in silico molecular target prediction helps find novel therapeutic agents. Among L. shawii metabolites, emodin is suggested for further studies as an agent for drug development against pathogenic bacteria and cancer.

Background: Myrrh extract is a well-known medicinal plant with significant therapeutic benefits attributed to the activity of its diverse metabolites. It has promising activity against cancer and inflammatory diseases, and could serve as a potential therapeutic alternative since most therapeutic agents have severe side effects that impair quality of life. Method: The current study identified the active metabolites from the myrrh resin methanolic extract. Then, the extracts were tested for in vitro anti-inflammatory and anti-cancer activity using cancer cell lines and Tamm-Horsfall Protein 1 (Thp-1)-like macrophage cell lines. Furthermore, using an in vivo rat model, the extracts’ anti-inflammatory and wound-healing activity was investigated. In addition, in silico predictions of the myrrh constituents highlighted the pharmacokinetic properties, molecular targets, and safety profile, including cytochrome P 450 (CYP) inhibition and organ toxicity. Results: Nine secondary metabolites were identified, and computational predictions suggested a good absorption profile, anticancer, anti-inflammatory, and wound-healing effects. The myrrh extract had moderate cytotoxic activity against both HL60 and K562 leukemia cell lines and the KAIMRC1 breast cancer cell line. Myrrh caused a dose-dependent effect on macrophages to increase the reactive oxygen species (ROS) levels, promote their polarization to classically activated macrophages (M1) and alternatively activated macrophages (M2) phenotypes, and consequently induce apoptosis, highlighting its ability to modulate macrophage function, which could potentially aid in several desired therapeutic processes, including the resolution of inflammation, and autophagy which is an important aspect to consider in cancer treatment. The topical application of myrrh improved wound healing, with no delayed inflammatory response, and promoted complete re-epithelization of the skin, similar to the positive control. In conclusion, we provide evidence for the methanolic extract of myrrh having cytotoxic activity against cancer cells and anti-inflammatory wound-healing properties, which may be attributed to its role in modulating macrophage function. Furthermore, we suggest the active constituents responsible for these properties, which warrants further studies focusing on the precise roles of the active metabolites.

Introduction: Biogenic silver nanoparticles (AgNPs) may be a feasible therapeutic option in the research and development towards selectively targeting specific cancers and microbial infections, lending a role in precision medicine. In-silico methods are a viable strategy to aid in drug discovery by identifying lead plant bioactive molecules for further wet lab and animal experiments. Methods: Green synthesis of M-AgNPs was performed using the aqueous extract from the Malvaviscus arboreus leaves, characterized using UV spectroscopy, FTIR, TEM, DLS, and EDS. In addition, Ampicillin conjugated M-AgNPs were also synthesized. The cytotoxic potential of the M-AgNPs was evaluated using the MTT assay on MDA-MB 231, MCF10A, and HCT116 cancer cell lines. The antimicrobial effects were determined using the agar well diffusion assay on methicillin-resistant S. aureus (MRSA) and S. mutans, E. coli, and Klebsiella pneumoniae. Additionally, LC-MS was used to identify the phytometabolites, and in silico techniques were applied to determine the pharmacodynamic and pharmacokinetic profiles of the identified metabolites. Results: Spherical M-AgNPs were successfully biosynthesized with a mean diameter of 21.8 nm and were active on all tested bacteria. Conjugation with ampicillin increased the susceptibility of the bacteria. These antibacterial effects were most predominant in Staphylococcus aureus (p < 0.0001). M-AgNPs had potent cytotoxic activity against the colon cancer cell line (IC₅₀=29.5 μg/mL). In addition, four secondary metabolites were identified, Astragalin, 4-hydroxyphenyl acetic acid, Caffeic acid, and Vernolic acid. In silico studies identified Astragalin as the most active antibacterial and anti-cancer metabolite, binding strongly to the carbonic anhydrase IX enzyme with a comparatively higher number of residual interactions. Discussion: Synthesis of green AgNPs presents a new opportunity in the field of precision medicine, the concept centered on the biochemical properties and biological effects of the functional groups present in the plant metabolites used for reduction and capping. M-AgNPs may be useful in treating colon carcinoma and MRSA infections. Astragalin appears to be the optimal and safe lead for further anti-cancer and anti-microbial drug development.

Introduction: This paper fulfills an identified need to study the mental health status of the population under situations like lockdown, thereby helping fill a persistent gap in Indian research on this issue, and present research on the impact of lockdown on mental health during epidemics is limited, especially in India. This study aims to scale the association between anxiety and sociodemographic factors during the coronavirus disease 2019 lockdown among the general Indian population.Methods: A descriptive cross-sectional nationwide study designed to enroll the general population. The inclusion criteria for this study were Indian citizens aged 18 years and above. The study was conducted from March 29, 2020, to April 12, 2020, using an online google questionnaire. The anxiety among respondents was detected and measured using a Generalized Anxiety Disorder (GAD) Scale, which consists of seven questions (in English), that is, GAD-7.Results: Responders were 392, and from these participants, the prevalence of anxiety was 25.3%. The predictors of anxiety were gender, religion, occupation as business/self-employed, marital status, family size, health status, and sleep deprivation based on the bivariate logistic regression analysis.Conclusion: This study reports the early prevalence of anxiety among the Indian population who were grounded at their homes during lockdown due to coronavirus pandemic in the country.

CXCR3 is a well-known receptor involved in immune cell recruitment and inflammation. Pathological inflammation leads to pain stimulation and hence nociception. Therefore, we decided to review the recent research on CXCR3 to identify its precise role in the modulation of pain in a variety of clinical conditions targeting various regions of the body. Studies were selected from PubMed Medline, which relate CXCR3 to the progression of diseases with either bone cancer pain, neuropathic pain, cystitis pain, osteoarthritis and rheumatoid arthritis pain, dental pain, in particular, periodontitis and pulpitis. In all the diseases studied, a high prevalence of CXCR3 and/or its ligand were identified where CXCR3 is a key player in the pathophysiological process of many inflammatory conditions. CXCR3 and its ligands, particularly CXCL10, modulate nociception via actions in the dorsal root ganglia and dorsal horn of the spinal cord, in cases of bone cancer pain, neuropathic, and joint pain. However, with the other studied disease, no direct link to pain has been made, although it contributes to the pathological progression of the diseases and hence would be a causal factor for the pain. Furthermore, CXCR3 appears to play a role in desensitizing the opioid receptor in the descending modulatory pathway within the brain stem as well as modulating opioid-induced hyperalgesia in the dorsal horn of the spinal cord. Further research is required for understanding the exact mechanisms of CXCR3 in pain modulation centrally and peripherally. A greater understanding of the immunological activities and pharmacological consequence of CXCR3 and its ligands could help in the discovery of newer drugs for modulating pain arising from pathogenic or inflammatory sources. Given the significance of the CXCR3 for nociception, its utilization may prove to be beneficial as a target for analgesia.

The broad application of metal nanoparticles in different fields encourages scientists to find alternatives to conventional synthesis methods to reduce negative environmental impacts. Herein, we described a safe method for preparing silver nanoparticles (J-AgNPs) using Jatropha integerrima leaves extract as a reducing agent and further characterize its physiochemical and pharmacological properties to identify its therapeutic potential as a cytotoxic and antimicrobial agent. The biogenic synthesized J-AgNPs were physiochemically characterized by ultraviolet-visible spectroscopy, dynamic light scattering (DLS), transmission electron microscope (TEM), and energy-dispersive X-ray spectroscopy. HPLC-DAD, followed by LC/MS and the Fourier-transform infrared spectroscopy (FTIR), was applied to detect the biomolecules of J. integerrima involved in the fabrication of NPs. Furthermore, J-AgNPs and the ampicillin-nanocomposite conjugate were investigated for their potential antibacterial effects against four clinical isolates. Finally, cytotoxic effects were also investigated against cancer and normal cell lines, and their mechanism was assessed using TEM analysis and confocal laser scanning microscopy (LSM). Ag ions were reduced to spherical J-AgNPs, with a zeta potential of −34.7 mV as well as an average size of 91.2 and 22.8 nm as detected by DLS and TEM, respectively. HPLC GC/MC analysis identified five biomolecules, and FTIR suggested the presence of proteins besides polyphenolic molecules; together, these molecules could be responsible for the reduction and capping processes during NP formation. Additionally, J-AgNPs displayed a strong antibacterial effect, although the ampicillin conjugated form had a very weak antibacterial effect. Furthermore, the NPs caused a reduction in cell viability of all the treated cells by initiating ultrastructural changes and apoptosis, as identified by TEM and LSM analysis. Therefore, J-AgNPs can be formed using the leaf extract from the J. integerrima plant. Furthermore, J-AgNPs may serve as a candidate for further biochemical and pharmacological testing to identify its therapeutic value.