A comprehensive review of apigenin a dietary flavonoid: biological sources, nutraceutical prospects, chemistry and pharmacological insights and health benefits.

A multitude of plant-derived bioactive compounds have shown significant promise in preventing chronic illnesses, with flavonoids constituting a substantial class of naturally occurring polyphenolic compounds. Apigenin, a flavone identified as 4',5,7-trihydroxyflavone, holds immense promise as a preventative agent against chronic illnesses. Despite its extensive research and recognized nutraceutical value, its therapeutic application remains underexplored, necessitating further clinical investigations. This review delves into the biological sources, nutraceutical prospects, chemistry, pharmacological insights, and health benefits of apigenin. Through multifaceted analytical studies, we explore its diverse pharmacological profile and potential therapeutic applications across various health domains. The manuscript comprehensively examines apigenin's role as a neuroprotective , anti-inflammatory compound, and a potent antioxidant agent. Additionally, its efficacy in combating cardiovascular diseases, anti-diabetic properties, and anticancer potential has been discussed. Furthermore, the antimicrobial attributes and the challenges surrounding its bioavailability, particularly from herbal supplements have been addressed. Available in diverse forms including tablets, capsules, solid dispersions, co-crystals, inclusion complexes and nano formulations. Additionally, it is prevalent as a nutraceutical supplement in herbal formulations. While strides have been made in overcoming pharmacokinetic hurdles, further research into apigenin's clinical effectiveness and bioavailability from herbal supplements remains imperative for its widespread utilization in preventive medicine.

Dental pulp stem cell secretome ameliorates d-galactose induced accelerated aging in rat model.

Advancing age is associated with several diseases and disorders due to multiorgan atrophy. The increasing proportion of elderly humans demands the identification of means to counteract aging and age-associated disorders. There is an increased depletion of stem cells in the aged organs, resulting in their inability to repair the damage and hence organ degeneration. Stem cell therapy has been implicated in counteracting aging and shown promise. However, the use of stem cells encounters several side effects and complications such as handling and storage of the cells for transplantation purpose. Stem cells secretome has proven to be of significant importance in a variety of disorders. In this study, we have shown that secretome derived from dental pulp stem cells (DPSCs) can reverse the age-associated degeneration induced by chronic exposure to d-galactose in a rat model. The secretome was able to increase muscle grip strength and animal activity. Secretome also improved the kidney function and hepatic biochemistry similar to healthy controls as evaluated by renal function test and Fourier-transform infrared spectroscopy. We also showed that secretome reduced the levels of monoamine oxidase and acetylcholinesterase in the brain and liver, indicating aging reversal. Finally, proteomic profiling of DPSCs secretome revealed the presence of 13 proteins which have antiaging functions. Thus, our study provides first proof of concept that DPSCs secretome can render protection against d-galactose induced accelerated aging.

Tafenoquine for Plasmodium vivax malaria: Concerns regarding efficacy & safety.

Plasmodium vivax (P. vivax) malaria is a major problem in various countries such as America, Southeast Asia, Africa and the Eastern Mediterranean. The major barrier in controlling P. vivax malaria is its ability to remain in the liver as a hypnozoite form which is responsible for relapse of P. vivax malaria; hence it is necessary to target both the blood (schizont) as well as the liver (hypnozoite) stages of P. vivax to prevent its relapse. A number of factors limit the use of primaquine (PQ), the currently available therapy for P. vivax (hypnozoite stage), such as haemolysis in glucose-6-phosphate dehydrogenase-deficient patients and being contraindicated in pregnant women. Another problem associated with PQ is the poor adherence rate to the 14-day treatment regimen. Single-dose tafenoquine (TQ), an 8-aminoquinoline, has recently been approved by the U.S. FDA for the treatment of P. vivax malaria along with a blood schizonticidal. TQ is active against all stages of P. vivax lifecycle. In published studies, TQ is considered a better alternative to PQ in terms of adherence, but there are some concerns regarding its safety, efficacy and study designs of trials conducted on TQ. In this context, this review, discusses the potential safety concerns, efficacy data, summary and an appraisal of findings of the important published trials of TQ.

Assessment of Elastic-Plastic Fracture Behavior of Cortical Bone Using a Small Punch Testing Technique.

The fracture properties of cortical bone are directly coupled to its complex hierarchical structure. The limited availability of bone material from many anatomic locations creates challenges for assessing the effect of bone heterogeneity and anisotropy on fracture properties. The small punch technique was employed to examine the fracture behavior of cortical bone in terms of area under the curve values obtained from load-load point displacement behavior. Fracture toughness of cortical bone was also determined in terms of J-toughness values obtained using a compact tension (CT) test. Area under the curve values obtained from the small punch test were correlated with the J-toughness values of cortical bone. The effects of bone density and compositional parameters on area under the curve and Jtoughness values were also analyzed using linear and multiple regression analysis. Area under the curve and J-toughness values are strongly and positively correlated. Bone density and %mineral content are positively correlated with both area under the curve and J-toughness values. The multiple regression analysis outcomes support these results. Overall, the findings support the hypothesis that area under the curve values obtained from small punch tests can be used to assess the fracture behavior of cortical bone.

Transplantation of hepatocytes from genetically engineered pigs into baboons.

BACKGROUND: Some patients with acute or acute-on-chronic hepatic failure die before a suitable human liver allograft becomes available. Encouraging results have been achieved in such patients by the transplantation of human hepatocyte progenitor cells from fetal liver tissue. The aim of the study was to explore survival of hepatocytes from genetically engineered pigs after direct injection into the spleen and other selected sites in immunosuppressed baboons to monitor the immune response and the metabolic function and survival of the transplanted hepatocytes. METHODS: Baboons (n=3) were recipients of GTKO/hCD46 pig hepatocytes. All three baboons received anti-thymocyte globulin (ATG) induction and tapering methylprednisolone. Baboon 1 received maintenance immunosuppressive therapy with tacrolimus and rapamycin. Baboons 2 and 3 received an anti-CD40mAb/rapamycin-based regimen that prevents sensitization to pig solid organ grafts. The baboons were euthanized 4 or 5 weeks after hepatocyte transplantation. The baboon immune response was monitored by the measurement of anti-non-Gal IgM and IgG antibodies (by flow cytometry) and CFSE-mixed lymphocyte reaction. Monitoring for hepatocyte survival and function was by (i) real-time PCR detection of porcine DNA, (ii) real-time PCR for porcine gene expression, and (iii) pig serum albumin levels (by ELISA). The sites of hepatocyte injection were examined microscopically. RESULTS: Detection of porcine DNA and porcine gene expression was minimal at all sites of hepatocyte injection. Serum levels of porcine albumen were very low-500-1000-fold lower than in baboons with orthotopic pig liver grafts, and approximately 5000-fold lower than in healthy pigs. No hepatocytes or infiltrating immune cells were seen at any of the injection sites. Two baboons (Baboons 1 and 3) demonstrated a significant increase in anti-pig IgM and an even greater increase in IgG, indicating sensitization to pig antigens. DISCUSSION AND CONCLUSIONS: As a result of this disappointing experience, the following points need to be considered. (i) Were the isolated pig hepatocytes functionally viable? (ii) Are pig hepatocytes more immunogenic than pig hearts, kidneys, artery patch grafts, or islets? (iii) Does injection of pig cells (antigens) into the spleen and/or lymph nodes stimulate a greater immune response than when pig tissues are grafted at other sites? (iv) Did the presence of the recipient's intact liver prevent survival and proliferation of pig hepatocytes? (v) Is pig CD47-primate SIRP-α compatibility essential? In conclusion, the transplantation of genetically engineered pig hepatocytes into multiple sites in immunosuppressed baboons was associated with very early graft failure. Considerable further study is required before clinical trials should be undertaken.

Impact of regulatory spin of pioglitazone on prescription of antidiabetic drugs among physicians in India: A multicentre questionnaire-based observational study.

Background & objectives: Pioglitazone was suspended for manufacture and sale by the Indian drug regulator in June 2013 due to its association with urinary bladder carcinoma, which was revoked within a short period (July 2013). The present questionnaire-based nationwide study was conducted to assess its impact on prescribing behaviour of physicians in India. Methods: Between December 2013 and March 2014, a validated questionnaire was administered to physicians practicing diabetes across 25 centres in India. Seven hundred and forty questionnaires fulfilling the minimum quality criteria were included in the final analysis. Results: Four hundred and sixteen (56.2%) physicians prescribed pioglitazone. Of these, 281 used it in less than the recommended dose of 15 mg/day. Most physicians (94.3%) were aware of recent regulatory events. However, only 333 (44.8%) changed their prescribing pattern. Seventeen of the 416 (4.1%) physicians who prescribed pioglitazone admitted having come across at least one type 2 diabetes mellitus patient (T2DM) who had urinary bladder carcinoma, and of these 13 said that it was in patients who took pioglitazone for a duration of more than two years. Only 7.8 per cent of physicians (n=58) categorically advocated banning pioglitazone, and the rest opined for its continuation or generating more evidence before decision could be taken regarding its use in T2DM. Interpretation & conclusions: Majority of the physicians though were aware of the regulatory changes with regard to pioglitazone, but their prescribing patterns were not changed for this drug. However, it was being used at lower than the recommended dose. There is a need for generating more evidence through improved pharmacovigilance activities and large-scale population-based prospective studies regarding the safety issues of pioglitazone, so as to make effectual risk-benefit analysis for its continual use in T2DM.

Myofibrillar Myopathy Presenting as Neonatal Intestinal Pseudo-Obstruction: An Extremely Rare Entity.

BACKGROUND: Although the most common cause of neonatal intestinal pseudoobstruction (IP) is Hirschprungs disease, rarely myofibrillar myopathy can cause the same. CASE REPORT: This 31+4/7 male infant at autopsy had marked narrowing of the jejunum (0.9 cm long), and colon (7.0 cm long) markedly narrowed segments of the jejunum and large intestine, were noted respectively. Sections from these segments showed eosinophilic periodic acid Schiff stain and desmin positive cytoplasmic inclusion bodies in the myocytes. Transmission electron microscopy performed revealed the presence of abnormal granulofilamentous material around the atrophic sarcomeres, subsarcolemmal rod-shaped and globoid fibrillar inclusions in the intestinal, skeletal, and cardiac myocytes, suggesting a myofibrillar myopathy. CONCLUSION: Pure phenotypic neonatal IP presentation in a myofibrillar myopathy is extremely rare and not reported in the literature. Along with other common causes of neonatal IP, neuromuscular causes should also be investigated.

Pig kidney graft survival in a baboon for 136 days: longest life-supporting organ graft survival to date.

The longest survival of a non-human primate with a life-supporting kidney graft to date has been 90 days, although graft survival > 30 days has been unusual. A baboon received a kidney graft from an α-1,3-galactosyltransferase gene-knockout pig transgenic for two human complement-regulatory proteins and three human coagulation-regulatory proteins (although only one was expressed in the kidney). Immunosuppressive therapy was with ATG+anti-CD20mAb (induction) and anti-CD40mAb+rapamycin+corticosteroids (maintenance). Anti-TNF-α and anti-IL-6R were administered. The baboon survived 136 days with a generally stable serum creatinine (0.6 to 1.6 mg/dl) until termination. No features of a consumptive coagulopathy (e.g., thrombocytopenia, decreased fibrinogen) or of a protein-losing nephropathy were observed. There was no evidence of an elicited anti-pig antibody response. Death was from septic shock (Myroides spp). Histology of a biopsy on day 103 was normal, but by day 136, the kidney showed features of glomerular enlargement, thrombi, and mesangial expansion. The combination of (i) a graft from a specific genetically engineered pig, (ii) an effective immunosuppressive regimen, and (iii) anti-inflammatory agents prevented immune injury and a protein-losing nephropathy, and delayed coagulation dysfunction. This outcome encourages us that clinical renal xenotransplantation may become a reality.

Inflammasome assembly in neurodegenerative diseases.

Neurodegenerative disorders are characterized by the progressive dysfunction and death of selectively vulnerable neuronal populations, often associated with the accumulation of aggregated host proteins. Sustained brain inflammation and hyperactivation of inflammasome complexes have been increasingly demonstrated to contribute to neurodegenerative disease progression. Here, we review molecular mechanisms leading to inflammasome assembly in neurodegeneration. We focus primarily on four degenerative brain disorders in which inflammasome hyperactivation has been well documented: Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), and the spectrum of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). We discuss shared and divergent principles of inflammasome assembly across these disorders, and underscore the differences between neurodegeneration-associated inflammasome activation pathways and their peripheral-immune counterparts. We examine how aberrant assembly of inflammasome complexes may amplify pathology in neurodegeneration, including misfolded protein aggregation, and highlight prospects for neurotherapeutic interventions based on targeting inflammasome pathways.

Potential approaches using teneligliptin for the treatment of type 2 diabetes mellitus: current status and future prospects.

INTRODUCTION: Based on pharmacological properties and results from clinical studies, teneligliptin has a great potential to be used as an alternate-day therapy and also the daily dose can be reduced to 10 mg. Clinical data also suggest its excellent efficacy and safety among older subjects. AREAS COVERED: We have reviewed and discussed potential approaches using teneligliptin for the treatment of type 2 diabetes mellitus (T2DM) including alternate-day therapy and reduction of dose from 20 mg to 10 mg per day. We have also discussed the potential of teneligliptin to address the needs of older patients with T2DM. EXPERT OPINION: It is an excellent option for use in older patients as studies in the geriatric population have shown encouraging results. Teneligliptin has a desirable pharmacokinetic profile that makes it a potential drug for use on an alternate-day basis. Teneligliptin has shown anti-diabetic efficacy even at a dose of 10 mg. These approaches may improve treatment satisfaction and patient compliance and can lower the cost; however, it is crucial to identify the subset of T2DM patients who can obtain maximum benefits. To verify these effects, large clinical investigations need to be planned and robust clinical evidence should be generated.

Alternate-day add-on therapy with dapagliflozin in patients with type 2 diabetes mellitus: potential benefits and concerns.

INTRODUCTION: Factors such as compliance, cost and safety play a major role in achieving the long-term goal in the management of type 2 diabetes mellitus (T2DM). Dapagliflozin carries a great potential of becoming an alternate-day therapy because of its favorable pharmacological properties. AREAS COVERED: In this review, we have discussed and hypothesized the potential of dapagliflozin as an alternate-day add-on drug in T2DM patients. We have discussed the properties by virtue of which it carries a potential to become an alternate-day therapy. We have also explained the potential benefits and concerns of using this approach. EXPERT OPINION: Alternate-day add-on therapy with dapagliflozin could be a promising approach in reducing the cost, improving the treatment satisfaction and reducing the adverse effects. However, this propsed indication demands an in-depth investigation among T2DM subjects who are not able to achieve glycemic control with standard monotherapy or combination therapy. Pilot studies or some small-scale investigator-initiated trials or academic clinical trials may be carried out to explore this concept. At the same time, large industry sponsored multicenter clinical trials including pharmacoeconomic analyses may be planned to have a more detailed investigation.

Piperlongumine inhibits diethylnitrosamine induced hepatocellular carcinoma in rats.

BACKGROUND: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. Piperlongumine (PL) has been claimed to have cytotoxic and HCC inhibitory effects in various cancer cell lines and xenograft models, but the chemopreventive potential of PL has not been studied in experimentally induced HCC yet. RESEARCH DESIGN: Twenty-four Wistar male rats were divided into four groups of six each, Group A: untreated control; Group B: Diethylnitrosamine (DEN) control (200 mg/kg), Group C: DEN + PL 10 mg/kg; and Group D: DEN + PL 20 mg/kg. Rats from all groups were assessed for liver cancer progression or inhibition by evaluating biochemical, cytokines, tumor markers, lipid peroxidation, and histological profiles. RESULTS: The liver enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP) levels, and lipid peroxidation were significantly decreased in Group C and Group D compared to Group B. Upregulation in the level of pro-inflammatory cytokines IL-1B, TNF-α, inflammatory mediator (NF-κB) and tumour marker alpha-fetoprotein (AFP) in Group B were brought down upon treatment with piperlongumine in a dose-dependent manner. Antitumor cytokine (IL-12) was upregulated in PL-treated rats compared to DEN control rats. DEN treated group (Group B) showed histological features of HCC, and in rats treated with PL (Groups C, D) partial to complete reversal to normal liver histoarchitecture was observed. CONCLUSIONS: The potential chemopreventive actions of piperlongumine may be due to its free radical scavenging and antiproliferative effect. Therefore, piperlongumine may serve as a novel therapeutic agent for the treatment of hepatocellular carcinoma.

Efficacy of Ferulic Acid in an Animal Model of Drug-Resistant Epilepsy: Beneficial or Not?

Background Lamotrigine (LTG) and subconvulsive doses of pentylenetetrazol (PTZ) as a model mimic drug-resistant epilepsy (DRE), which is a serious unmet medical condition. Previous evidence suggests an imperative role of neuroinflammation in the development of DRE. Various preclinical models of brain injury have reported potent anti-inflammatory and antioxidant properties of ferulic acid (FA). Therefore, its efficacy against intractable epilepsy is worthwhile to study. Materials and methods The present study evaluated the efficacy of FA in LTG and PTZ-induced refractory seizures in mice. On every alternate day for 38 days, LTG (5mg/kg) was injected before PTZ (30-40mg/kg) to establish a murine model of DRE. Animals were treated with two doses of FA (40, 80 mg/kg). All the animals were assessed for seizure score and the latency of seizures every alternate day till the end of the study. Histopathological score and the levels of pro-inflammatory mediators, interleukin-1ßeta (IL-Iß), tumor necrosis factor-alpha (TNF-α), and matrix metalloproteinase-9 (MMP-9) were quantified in the brain tissue of these mice.  Results Ferulic acid (FA) neither decreases the LTG and PTZ-induced refractory seizures score nor increases the latency to develop seizures. In addition, the injury to hippocampal neurons and the levels of pro-inflammatory cytokines were comparable with two doses of FA in treated mice. Conclusion In the present study, single-dose FA treatment does not show any beneficial effect against the LTG/PTZ model of DRE. Therefore, its single-dose administration might not be beneficial against the DRE model.

Dimethyl Fumarate Ameliorates Paclitaxel-Induced Neuropathic Pain in Rats.

Background Paclitaxel (PTX)-induced peripheral neuropathy (PIPN) is nonresponsive to the currently available analgesics. Previous studies have shown the role of oxidative stress and central sensitization in the development of peripheral neuropathy. Dimethyl fumarate (DMF) acts as a nuclear factor erythroid-2-related factor 2 (Nrf2) activator with neuroprotective benefits and is approved for use in multiple sclerosis. Materials and methods In the current research, we evaluated the efficacy of DMF on paclitaxel-induced peripheral neuropathy in rats. Every alternate day for one week, paclitaxel 2 mg/kg dose was injected to establish a rat model of PIPN. Animals were treated with 25 mg/kg and 50 mg/kg of DMF. All the animals were assessed for thermal hyperalgesia, cold allodynia, and mechanical allodynia once a week. The gene expression of Nrf2 and the levels of pro-inflammatory mediators (interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α), and IL-1ß) were quantified in the sciatic nerves of these rats. The levels of p38 mitogen-activated protein kinase (MAPK) and brain-derived neurotrophic factor (BDNF) were quantified in the dorsal horn of the spinal cord. Results DMF significantly attenuated paclitaxel-induced thermal hyperalgesia and cold/mechanical allodynia. A significant decrease in the levels of pro-inflammatory cytokines with the levels of p38 MAPK and BDNF was observed in the DMF-treated animals. DMF treatment significantly upregulated the gene expression of Nrf2 in the sciatic nerve. Conclusion These findings suggest that DMF prevented the development of PIPN in rats through the activation of Nrf2 and the inhibition of p38 MAPK and BDNF.

Congenital right coronary artery-to-right ventricular outflow tract fistula device closure with migration: retrieval of device after eight years.

Coronary artery congenital fistulas are rare disorders. Transcatheter closure is the primary method of closure. Device migration is a known complication, for which surgical retrieval is required.

Molecular docking analysis of piperlongumine with different apoptotic proteins involved in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. Numerous signalling pathways are involved in hepatocellular carcinoma. Piperlongumine is a potential candidate for the treatment of hepatocellular carcinoma. Therefore, it is of interest to document the molecular docking analysis of piperlongumine with different apoptotic proteins involved in Hepatocellular Carcinoma. Piperlongumine was docked with the HCC targets such as vascular endothelial growth factor (VEGF), epidermal growth factor receptor, Aurora-2, Nuclear factor Kappa-B (NF-KB), Jak2 Kinase, Fibroblast growth factor receptor 4, Bcl-2-like protein 1,Apopain, and Apoptosis regulator Bcl-2 using in-silico technique with the software grid-based ligand docking with energies. Piperlongumine exhibited the highest negative energy value (E-value) of -6.58 kcal/mol with vascular endothelial growth factor receptor 2, followed by -5.46, -5.34, -5.31, and -5.29 kcal/mol with 1M17, 2BMC, 1SVC, 4C61, 4XCU with epidermal growth factor receptor, aurora-2, nuclear factor Kappa-B (NF-KB), Jak2 kinase, and fibroblast growth factor receptor 4 (FGFR4), respectively for further consideration.

Traditional Chinese Medicine Body Constitutions and Psychological Determinants of Depression among University Students in Malaysia: A Pilot Study.

Depression is commonly observed in university students, who are a high risk group for developing psychiatric disorders during adulthood. This study aimed to determine the prevalence of depression and its traditional Chinese medicine body constitutions and psychological determinants among university students in Malaysia. A cross-sectional pilot study was conducted between 9 and 28 September 2020 among 80 university students in Malaysia. Participants completed online survey questionnaires, including the validated Patient Health Questionnaire (PHQ-9), Constitution in Chinese Medicine Questionnaire (CMCQ), Dysfunctional Attitude Scale (DAS), Depression Anxiety Stress Scale (DASS-21) stress subscale, Perceived Stress Scale (PSS-10), and Rosenberg Self-Esteem Scale (RSES), which assess depression, body constitution, dysfunctional attitude, stress, perceived stress, and self-esteem. Multiple linear regression analyses were performed to determine the associated risk factors for depression. The overall prevalence of depression among university students was 33.8%. The multiple regression analysis showed a significant relationship between depression and qi-stagnation constitution (B = 0.089, p = 0.011), balanced constitution (B = -0.077, p = 0.049), and self-esteem (B = -0.325, p = 0.001). Our findings suggest that some traditional Chinese medicine body constitutions and self-esteem are significant risk factors affecting depression among university students. Identifying risk factors of depression is vital to aid in the early detection of depression among university students.

Ten days vs. 14 days antibiotic therapy in culture-proven neonatal sepsis.

BACKGROUND: There are no evidence-based guidelines for the treatment of neonatal sepsis although standard text books recommend 14 days of antibiotics for blood culture-proven neonatal sepsis. OBJECTIVE: The present study compared the effectiveness of a 10-day course of antibiotic therapy with the conventional 14-day course in blood culture-proven neonatal sepsis. METHODS: Infants ≥ 32 weeks and ≥ 1.5 kg weight with blood culture-proven sepsis were randomized to either 10-day (study group) or 14-day (control group) therapy on Day 7 of appropriate antibiotic therapy, if they were in clinical remission and were C-Reactive Protein (CRP) negative. The primary outcome was treatment failure within 28 days defined by either positive CRP or positive blood culture or clinical relapse. RESULTS: The baseline characteristics were comparable between the two groups. There was one treatment failure in each group. The duration of hospital stay was significantly shorter in the 10-day treatment group. CONCLUSION: Ten-day antibiotic therapy is as effective as 14-day therapy in blood culture-proven neonatal sepsis, if the infant has achieved clinical remission by Day 7 of therapy.

Repurposing Potential of Ketamine: Opportunities and Challenges.

Ketamine is a noncompetitive antagonist of the N-methyl-D-aspartate (NMDA) receptor which also interacts with various other receptors that account for its myriad actions. Originally approved as a general anesthetic, it is being explored to be repurposed for numerous other indications such as depressive disorders, suicidal ideation, substance-use disorders, anxiety disorders, chronic pain, refractory status epilepticus, and bronchial asthma exacerbations. Numerous trials are ongoing for the same. The nasal spray of esketamine, a more potent S (+) enantiomer of ketamine, has been approved by the United States Food and Drug Administration (USFDA) for treatment-resistant depression along with the oral antidepressants. However, there are concerns about its safety on long term use, given its psychedelic effects and potential abuse. In this review, we discuss repurposing ketamine for potential therapeutic use and about the safety concerns related to ketamine and esketamine.