Ketamine, a non-competitive N-methyl-D-aspartate receptor antagonist, has emerged as an effective therapeutic agent for the management of treatment-resistant depression. Repeated treatments with ketamine show rapid, robust, and sustained antidepressant effects. Despite the large body of evidence, key concerns include adverse effects such as dissociative symptoms, hemodynamic instability, and the risk of abuse with long-term ketamine therapy. This narrative review provides an overview of the neurobiological mechanisms underlying ketamine’s antidepressant effects, its basic pharmacodynamics, and its safety profile. The clinical evidence regarding ketamine’s efficacy in depression is also summarized, and the need for further research on the long-term effects of ketamine therapy, the development of agents with similar antidepressant effects but fewer adverse effects or potential for abuse, and the identification of biomarkers to predict the response to ketamine is highlighted.

The polymer’s slow hydrolysis facilitates the sustained release of the immunogen, stabilizing the antigen encapsulated within the microspheres. As a result, microspheres ranging from 40 µm to 70 µm in diameter can be formed. This innovative microsphere formulation allows for efficient uptake by macrophages and other antigen-presenting cells. This study aimed to use biocompatible polymethyl methacrylate microspheres for the controlled delivery of antigens.

The potency of various formulations containing encapsulated tetanus toxoid (TT) with polymethyl methacrylate polymer microspheres was assessed using the toxin neutralization and challenge methods. The neutralization test was conducted on pooled sera two weeks after the initial immunization and weekly for four weeks following the booster dose administration. Scanning electron micrographs of the microspheres revealed drug leaching from spherical granular matrices.

The injection site showed a higher distribution of smaller microparticles, resulting in depot release. The polymer coating’s thickness was significantly lower compared to the 25% polymer microspheres. Concentrations ranging from 0.00024 mL to 0.00030 mL caused significant tetanic paralysis. Two weeks after the initial immunization, the antigenic activity of TT was below the minimum threshold, possibly due to insufficient levels of antigenic TT within the system within seven days post-immunization. The polymethacrylate microsphere elicited a notable immune response, but only the polymer concentration of 25% w/v met the I.P. requirements; lower polymer concentrations were ineffective.

The polymer’s slow hydrolysis facilitates the sustained release of the immunogen, stabilizing the antigen encapsulated within microspheres. Consequently, microspheres ranging from 40 µm to 70 µm in diameter can be assembled. This innovative microsphere formulation allows for efficient uptake by macrophages and other antigen-presenting cells.

Chlorella vulgaris is a green, photosynthetic microalga in the phylum Chlorophyta. The goal of our study was to perform a bioinformatics analysis of Photosystem I P700 chlorophyll a apoprotein A2, one of its photosynthesis-related proteins, and to hunt for potent bioactive peptides.

To generate peptides and estimate the safety and efficacy of each bioactive peptide, we employed the tools BIOPEP-UWM™, PeptideRanker, DBAASP, and ToxinPred. PepDraw was used to understand the physicochemical properties and primary chemical structures of the selected bioactive peptides.

The liberated peptides exhibit up to 17 distinct bioactivities, as shown by the in silico digestion of the protein using several proteolytic enzymes. The peptides with bioactivities are listed as angiotensin-converting enzyme inhibitor, dipeptidyl peptidase IV inhibitor, dipeptidyl peptidase III inhibitor, antioxidative, renin inhibitor, glucose uptake stimulator, neuropeptide regulator (regulating stomach mucosal membrane activity and ion flow), antithrombotic, anti-amnestic, CaMPDE inhibitor, activators of ubiquitin-mediated proteolysis, alpha-glucosidase inhibitor, immunomodulating, calcium-binding, antibacterial, anti-inflammatory, and hypotensive agent. Using the Database of Antimicrobial Activity and Structure of Peptides (DBAASP) prediction method, the antibacterial activity of the released peptides was predicted, highlighting the existence of potent antibacterial peptides. An examination of their physicochemical properties revealed that most peptides are low molecular weight, mildly acidic, and moderately water-soluble. To further establish the non-toxicity profile of the released peptides (sequence length > 3), a ToxinPred analysis was performed, which revealed that most of the peptides are non-toxic. According to the allergenicity analysis, most of the top-ranked peptides are likely non-allergenic.

Thus, our study reveals a less labor-intensive method for discovering new therapeutic targets derived from C. vulgaris, which hold both pharmacological and medical significance.

The SARS-CoV-2 virus Spike (S) protein binds to an angiotensin-converting-enzyme 2 receptor (ACE2) on the surface of cells to allow viral DNA entry. Given the plenitude of FDA-approved antiviral drugs, we aimed to screen those that may be repurposed for treating SARS-CoV-2 infections.

Using the crystal structure of SARS-CoV-2 Spike complexed with ACE2 (PDB ID: 6VW1) as a template, we developed a pharmacophore model of functional centers of the SARS-CoV-2 Spike protein inhibitor-binding domain. The conformations of these compounds underwent 3D fingerprint similarity clusterization, followed by docking of possible conformers to the binding site of ACE2. A similar protocol was followed for a set of randomly-selected compounds. Molecular dynamics was performed to confirm the stability of the selected drugs bound to ACE2.

Based on the model, we conducted a pharmacophore search from a conformational database of FDA-approved drugs. From the 379 compounds identified as potential inhibitors of SARS-CoV-2, 152 compounds with the best scores were selected based on maximal hydrogen-bond and hydrophobic interactions. The average free energies of the docking interaction for the selected compounds were better than those of random compounds. The obtained drug list includes inhibitors of HIV, HCV, CMV, ZIKV, HMPV, and RVFV as well as a set of drugs that have demonstrated some activity in MERS, SARS-CoV, and SARS-CoV-2 therapy.

Using a set of computational methods, we predicted the FDA-approved drugs that might bind to the interface of ACE2 protein and Spike protein of SARS-CoV-2 and prevent binding between Spike and ACE2. In further works, we recommend testing the selected compounds for treatment of COVID-19.

Thyroid disorder and diabetes are associated endocrine disorders. Patients with either one of the disorders are at great risk of developing the other. The co-existence of type-2 diabetes mellitus (T2DM) and hypothyroidism with clinical evidence of effect on one another has not been reported until today.

This prospective study involved 702 patients. Each participant’s blood sugar levels and thyroid profiles were statistically analyzed using unpaired t-test.

The incidence of hypothyroidism and hyperthyroidism in diabetic patients was 20.2% and 1.71% respectively, while the incidence of type-1 diabetes mellitus and T2DM in thyroid dysfunction patients was 0.56% and 19.03% respectively. The mean fasting blood sugars and postprandial blood sugar levels, triiodothyronine, thyroxine and Thyroid stimulating hormone levels of hypothyroid patients with T2DM (157.2 ± 4.779, 231.7 ± 6.291, 1.123 ± 0.065, 8.643 ± 1.519 and 12.22 ± 1.974) were not significantly different (p > 0.05) from those in T2DM patients with hypothyroidism (153.6 ± 7.181, 236.6 ± 9.504, 1.091 ± 0.013, 7.971 ± 1.024 and 12.09 ± 1.48). These findings were above the normal range (fasting blood sugar of 70–110 mg/dL; postprandial blood sugar of >140 mg/dL) thyroid stimulating hormone of 0.39–6.16 mIU/L in both type of patients, with the exception of triiodothyronine and thyroxine.

We report clinical evidence of association between hypothyroidism and diabetes mellitus with the highest incidence of hypothyroidism in T2DM with four major findings, suggesting regular thyroid and glycemic level evaluations for diabetic and hypothyroid patients respectively. Thus adjustment of dosage of levothyroxine is necessary, with prompt monitoring and reduction of the dose of insulin or oral hypoglycemic drugs to avoid hypoglycemia and its complications.

Compositae species are applied as whole or part of the feed stock for animals and poultry. However, rabbits display varied preferences in their consumption of these plants, following the order of: Melanthera scandens (MS) > Synedrella nodiflora (SN) > Aspilia africana (AA) > Ageratum conyzoides (AC). This preference profile may be due to variation in chemical composition, flavor or toxicity of the plants. The rabbits in our farm feed on 100% MS or SN with excellent performance. This study, therefore, is set to: obtain the methanol extract of these plants, screen them for their antibacterial activity, determine their toxicity and investigate the chemical composition of their n-hexane fraction (volatile constituents).

Crushed leaves of MS, AC, AA and SN were extracted with methanol using soxhlet extraction technique to obtain the methanol extract of each plant. Phytochemical examination, antibacterial activity determination (using the agar-well diffusion technique) and toxicity studies (using experimental white albino mice) were carried out on the methanol extracts. Vacuum liquid chromatography (VLC) fractionation of each extract was carried out. The n-hexane fractions obtained from the VLC fractionation were subjected to gas chromatography-mass spectroscopy (GC-MS) analysis and the chemical constituents were identified.

Phytochemical screening showed the presence of alkaloids, steroids and tannins in all the extracts. The extracts exhibited varying degrees of antibacterial activities against bacterial strains used for this study. AC showed activity against tested microbes, having zones of inhibition ranging from 10 mm and 22 mm, with the exception of Bacillus stearothermophilus and Pseudomonas fluorescens. MS inhibited the growth of the microbes, having zones of inhibition ranging from 12 mm and 20 mm, with the exception of Bacillus anthracis, Bacillus stearothermophilus, Clostridium sporogens and Enterococcus faecalis. AA did not show activity against four of the tested microbes: Bacillus anthracis, Klebsiella pneumonia, Pseudomonas fluorescens and Enterococcus faecalis. SN however, inhibited the growth of all the bacterial strains tested, with the exception of Escherichia coli only. On the other hand, when streptomycin was used as a positive control, the growth of all the bacterial strains was inhibited, having zones of inhibition ranging from 15 mm and 22 mm. Toxicity study showed that the extracts were not toxic at the concentrations of 10 mg/kg through 1,000 mg/kg; however, at higher concentrations of 1,600 mg/kg through 2,500 mg/kg, the extracts became toxic. The LD50 was determined to be 1,275 mg/kg for all the extracts. GC-MS analysis showed the presence of 4-tetradecene in all of the extracts, except AC.

The varied preferences observed in rabbit consumption of these plants definitely have nothing to do with toxicity. The presence of various fatty acids and unsaturated hydrocarbons in the volatile components of the extracts, which influence the flavor, may be responsible for the wellness of rabbits and their relative preferences in consumption.

Despite the availability of several therapeutic strategies and many drugs, the ability to cure most cancers remains a challenge. Natural products have been used for the treatment of numerous diseases, including cancer. The present review delineates various preclinical studies performed in vitro and in vivo that explore the anticancer potential of berberine, an isoquinoline alkaloid found in numerous plants as a secondary metabolite. Berberine can kill various types of human cancer cells in an optimal concentration- and duration-dependent manner and inhibit the growth of various types of cancers in animal models by elevating oxidative stress. In addition, berberine suppresses cell migration, invasion and epithelial-to-mesenchymal transition in different types of cancer cells. Mechanistically, berberine can induce cancer cell DNA fragmentation/apoptosis through extrinsic and intrinsic pathways, autophagy and necrosis. The cytotoxic effects of berberine in different types of cancer cells are mediated by its ability to induce oxidative stress and cell cycle arrest, and inhibit cell migration, invasion and epithelial-to-mesenchymal transition as well as matrix metalloproteinases through the modulation of Wnt and β-catenin signaling. A single clinical study has shown some promise in gastric cancer patients. Though berberine is a relatively safe compound, it should not be prescribed to pregnant or lactating women to avoid adverse effects on developing fetuses and neonates.

Plants have been employed as medicine since time immemorial, and there has been a recent resurgence in the use of plants as medicines due to their little or no toxicity at the doses used for treatment of different ailments. This review discusses in detail the phytochemical and pharmacological activities of Jamun (Syzygium cumini), a tree belonging to family Myrtaceae, which has been credited with several medicinal properties in the traditional system of medicine, the Ayurveda. The different properties attributed to Jamun are sweet, sour, astringent, acrid, refrigerant, carminative, diuretic, and digestive. Research and practical use in traditional medicinal systems have found Jamun to be effective in treating leucorrhoea, gastric disorders, fever, diabetes, piles, stomachache, wounds, and dental, digestive and skin disorders. Some compounds in Jamun have antioxidant, antimicrobial, antiallergic, antidiabetic, antihyperlipidemic, anticancer, gastroprotective, hepatoprotective, cardioprotective and radioprotective activity. Finally, Jamun has been found to contain phytochemicals including anthroquinones, alkaloids, catechins, flavonoids, glycosides, steroids, phenols, tannins, saponins and cardiac glycosides. The diverse activities of Jamun may be due to its abilities to scavenge free radicals, increase antioxidant status of cells by increasing glutathione, glutathione peroxidase, catalase and/or superoxide dismutase, and to attenuate lipid peroxidation. In addition, it also suppresses the transcription of peroxisome proliferator-activated receptor, Nuclear factor kappa B, cyclooxygenase, inducible nitric oxide synthase, tumor necrosis factor alpha and other proinflammatory cytokines, accompanied by the up-regulation of nuclear factor erythroid 2-related factor 2 transcription, which is involved in regulating the antioxidant status of the cells.

Cannabis has been used medicinally for centuries and numerous species of this genus are undoubtedly amongst the primeval plant remedies known to humans. Cannabis sativa in particular is the most reported species, due to its substantial therapeutic implications that are owed to the presence of chemically and pharmacologically diverse cannabinoids. These compounds have long been used for the palliative treatment of cancer. Recent advancements in receptor pharmacology research have led to the identification of cannabinoids as effective antitumor agents. This property is accredited for their ability to induce apoptosis, suppress proliferative cell signalling pathways and promote cell growth inhibition. Evolving lines of evidence suggest that cannabinoid analogues, as well as their receptor agonists, may offer a novel strategy to treat various forms of cancer. This review summarizes the historical perspective of C. sativa, its potential mechanism of action, and pharmacokinetic and pharmacodynamic aspects of cannabinoids, with special emphasis on their anticancer potentials.