BACKGROUND: Constipation is one of the most frequent abnormalities of the gastrointestinal system that affects the patient's quality of life. Constipation is more common in women and affects them more frequently as they get older. Many constipated patients take over-the-counter drugs for treatment, but some do not respond to these medicines and need newer, more expensive drugs. Still, many patients are not completely satisfied with these medicines. Unlike other areas, constipation research is not given much importance. OBJECTIVE: This review discusses targets such as ClC-2, CFTR, opioid receptors, and 5HT-4 receptors, which are important in constipation therapy. The recent focus is also on the gut microbiome with the help of various randomized controlled trials. Pharmacological advances have also added novel targets such as IBAT, PAR-2, and intestinal NHE-3 for constipation treatment. METHODS: This review summarises the research on these targets collected from various databases. ClC-2 and CFTR are involved in intestinal chloride secretion followed by sodium or water, which increases stool passage. Non-cancer pain treatment with opioids targeting opiate receptors is considered in 40-90% of patients, which causes constipation as a side effect. On activation, 5HT-4 receptors increase gastrointestinal motility. IBAT is responsible for transporting bile acid into the liver. Bile acid will reach the colon by inhibiting IBAT, stimulating colonic motility, and providing a laxative effect. Activation of the ghrelin receptor results in prokinetic activity in both animals and humans. Intestinal NHE-3 mediates the absorption of Na+ and the secretion of hydrogen into the intestine. Many reports show that PAR-2 is involved in the pathogenesis of gastrointestinal diseases. The gut microbiota influences the peristaltic action of the intestine. CONCLUSION: Drugs working on these targets positively impact the treatment of constipation, as do the drugs that are currently in clinical trials acting on these targets. The results from the ongoing clinical trials will also provide some valuable information regarding whether these medications will meet the patients' needs in the future.

INTRODUCTION: Diseases caused by protozoa are one of the leading causes of death worldwide, especially in tropical regions such as Brazil. Chagas disease, leishmaniasis, and malaria are responsible for around 234 million cases and more than 400,000 deaths worldwide. Despite this scenario, drugs for these diseases have several limitations, which justifies the search for new treatments. Iron superoxide dismutase is a promising target for the drug design to treat patients with these diseases. It is a validated target and protects against oxidative stress. AIM: Thus, this systematic review aimed to synthesize evidence on the importance of superoxide dismutase in the drug design to treat patients with this protozoosis. METHOD: A search was performed for in vitro and in vivo studies, without publication and language restrictions, in MEDLINE (PubMed), LILACS (BVS), Science Direct, and EMBASE (Elsevier). Studies that pointed to the relationship between the reduction or increase in superoxide dismutase activity and the diseases were included. 23 studies were selected for the qualitative synthesis. RESULT: The results showed that the inhibition or reduction of the enzyme activity decreases the degree of infection and reinfection and improves the results in treating these diseases. In contrast, the increase in activity caused a high degree of survival and resistance of the parasites. CONCLUSION: However, the overall quality of evidence is low and more studies with methodological rigor are provided.

BACKGROUND: Epigenetic regulation of gene signalling is one of the fundamental molecular mechanisms for the generation and maintenance of cellular memory. Histone acetylation is a common epigenetic mechanism associated with increased gene transcription in the central nervous system (CNS). Stimulation of gene transcription by histone acetylation is important for the development of CNS-based long-term memory. Histone acetylation is a target for cognitive enhancement via the application of histone deacetylase (HDAC) inhibitors. The promising potential of HDAC inhibitors has been observed in the treatment of several neurodevelopmental and neurodegenerative diseases, Objective. This study assessed the current state of HDAC inhibition as an approach to cognitive enhancement and treatment of neurodegenerative diseases. Our analysis provides insights into the mechanism of action of HDAC inhibitors, associated epigenetic priming, and describes the therapeutic success and potential complications after unsupervised use of the inhibitors. RESULTS AND CONCLUSION: Several chromatin-modifying enzymes play key roles in the regulation of cognitive processes. The importance of HDAC signaling in the brain is highlighted in this review. Recent advancements in the field of cognitive epigenetics are supported by the successful development of various HDAC inhibitors, demonstrating effective treatment of mood-associated disorders. The current review discusses the therapeutic potential of HDAC inhibition and observed complications after mood and cognitive enhancement therapies.

The mucosal surfaces are the key site of the entrance, protection, and stability of several pathogens. Considering that >90% of pathogens gain access to the body via mucosal sites, using mucosal vaccination to generate protective immunity at mucosal sites could overcome. Some of the micro and nano carrier-based nasal delivery systems produce cellular, humoral and mucosal immunity. The nasal route vaccination may protect multiple distant mucosal sites like-rectal, vaginal, oral, and pulmonary. Also, it is a convenient and cost-effective vaccination mode with improved patient compliance. Several nasal vaccine delivery systems are currently being supplied in the form of liposomes, micro/nano particulates, which have shown immunity in animal models. Especially particulate nanovaccine has a special character related to long-term immunogenicity and high efficiency. The significance and the ability of the nasal route vaccination programs are unexplained and complications; therefore, effective delivery strategies will promote the production of nasal vaccines. The present study focuses on vaccine delivery strategies and their effects on the immune system. Also, the study discusses the benefits of mucosal-associated immune response over the conventional delivery system for vaccine via the nasal route.

BACKGROUND: The liver is one of the crucial organs in humans and is responsible for the regulation of diverse processes, including metabolism, secretion, and detoxification. Ingestion of alcohol and drugs, environmental pollutants, and irradiation are among the risk factors accountable for oxidative stress in the liver. Plant flavonoids have the potential to protect the liver from damage caused by a variety of chemicals. OBJECTIVE OF THE STUDY: The present study aims to summarize up-to-date information on the protective roles of plant flavonoids against liver damage. METHODOLOGY: The literature information on the hepatoprotective plant flavonoids was assessed through various databases, which were searched from their respective inception until March 2022. RESULTS: More than 70 flavonoids with hepatoprotective activity against a variety of models of liver toxicity have been reported across the literature. Among these are flavones (19), flavonols (30), flavanones (9), isoflavonoids (5), and biflavonoids (2). Several hepatoprotective mechanisms of action were reported in various classes of flavonoids, including flavones and flavonols (upregulation of the pro-survival ERK1/2 pathway; downregulation of apoptotic proteins, including Bax, Bcl-2, Bax, BH3, caspase-3, 8, 9, etc.), flavanones (downregulation of NF-κB, TNF-α, IL-1 β, IL-6, iNOS, etc.), isoflavonoids (downregulation of lipogenesis genes, such as SREBP-1c, LXRα, RXRα, PPARγ and ACC2, with concomitant upregulation of genes involved in β-oxidation, including AMPK and PPARα; inhibition of CYPs, such as CYP1A1, CYP1A2, CYP2B1, CYP2D6, CYP2E1 and CYP3A1/2). CONCLUSION: The present work demonstrated the effectiveness of plant flavonoids against hepatic damage. However, more studies need to be performed regarding the cytotoxicity, pharmacokinetics, and mechanisms of action of these very important cytoprotective flavonoids.

With a prevalence ranging from 16-21%, tinnitus is an irking neurological disorder, manifesting as the perception of a roar of cacophony without an external acoustic stimulus. Although tinnitus is a non-life-threatening symptom, tinnitus's negative repercussions, such as personality disturbances and social withdrawal, are daunting concerns despite a gamut of conventional and emerging treatment options. Tinnitus management is still a critical challenge that provides opportunities for clinicians, ENT (Ear/eye, nose and throat) physicians, and other specialists such as audiologists, psychiatrists, and psychologists. Among the new treatment modalities, Neuromonics tinnitus treatment (NTT) draws special attention in tinnitus management due to its mounting success rate. Nonetheless, unlike in developed countries like Australia, the United States, and the United Kingdom, the scanty awareness of NTT among Indian ENT specialists is a titanic setback for care providers. Because of this backdrop, this review emphasized the current perspectives on tinnitus management and the underlying principles and clinical efficacy of NTT. The challenges for tinnitus management can be met and reduced by suppressing tinnitus through motivation, counseling, cochlear implant, and psychotherapy.

Alzheimer's Disease (AD), affecting a large population worldwide, is characterized by the old population's loss of memory and learning ability. Cholinergic deficiency is associated with AD, and various cholinesterase inhibitors have been developed to treat AD, including naturally-derived inhibitors, synthetic analogs, and hybrids. Acetylcholinesterase (AChE) has obtained a renewed interest as a therapeutic target in Alzheimer's disease (AD) due to increased neural cells' function by increasing the concentration of acetylcholine. In this review, we reported the recent development of novel heterocyclic compounds such as coumarin-benzotriazole hybrids, carbazole derivatives, tacrine conjugates, N-benzyl-piperidine-aryl-acyl hydrazones hybrid, spiropyrazoline derivatives, coumarin-dithiocarbamate hybrids, etc. as AChE inhibitors for the treatment of Alzheimer disease. All the bioactive compounds show an effect on different cells and interact simultaneously with the catalytic active site (CAS) and peripheral anionic site (PAS) of AChE with a narrow range of IC50 values from 0.4 nm to 88.21 µm using Ellman's in vitro AChE assay method and show high BBB permeability in-vitro. In addition, the in-vitro fluorescence assay study using Amplex Red assay kits revealed that all the compounds could inhibit self-induced β-amyloid (Aβ) aggregation with the highest inhibition range from 31.4 to 82%. Furthermore, most of the compounds show a low toxicity profile during in vivo studies. The results suggest that all the compounds constitute promising leads for the AChE targeted approach for Alzheimer's disease.

INTRODUCTION: The association between triamcinolone hexacetonide (TH) and gold nanoparticles (GNPs) represents a promising treatment due to the potential anti-inflammatory and antioxidant effects of these compounds. In this study, we evaluated the effects of intra-articular treatment of TH associated with GNPs in a mechanical model of osteoarthritis (OA). METHODS: Fifty Wistar rats were divided into five groups: Sham; OA; OA+TH; OA+GNPs; OA+TH-GNPs. Both applications were performed 30 and 60 days after the model was induced. After 30 days of the last application, the animals were euthanized. RESULTS: Only the combined treatment with TH and GNPs promoted a reduction in pro-inflammatory cytokines and an increase in anti-inflammatory cytokines. The OA+TH-GNPs group obtained a significant reduction in the production of oxidants and oxidative damage markers while an increase in antioxidants. Histologically, all treated groups showed results of a significant increase in cartilage thickness and chondrocyte count, the OA+TH-GNPs group had similar behavior to the group without osteoarthritis, with significantly smaller amounts of chondrocytes than the OA group. CONCLUSION: The intra-articular use of TH associated with GNPs may be able to prevent the progression of the pathology and minimize joint degradation.