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1.
BMC Psychol ; 12(1): 352, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38879545

ABSTRACT

OBJECTIVE: Social media (SM), with its addictive nature and the accompanying psychosocial challenges such as stress, anxiety, and depression, is the primary factor exacerbating mental health problems and adversely impacting individuals' wellbeing. Our study's goal was to determine how SM affects employees' psychosocial behaviours and assess the various factors that contributed to the employee's excessive use of SM. METHODS: A cross-sectional correlational analysis was conducted. Using a relevant questionnaire on employees, the study was assessed to establish the relationship or association between SM addiction and psychosocial disorders like depression, anxiety, and stress. 200 people with a minimum age of 24 were enrolled in the study. The questionnaire contained the social networking addiction scale (SNAS) and the depression, anxiety, and stress-21 (DASS-21) scales; the data were statistically assessed. RESULTS: The association between SM addiction and psychosocial behaviours has been examined using statistical tools including descriptive statistics and the Chi-square analysis. SM addiction has a strong, statistically significant correlation with depression (p = 0.001), stress (p = 0.001), and anxiety (p = 0.001). CONCLUSION: This study discovered a connection between SM use and depression, stress, and anxiety among working employees, raising questions regarding worries about overuse and addiction to SM. Various factors influencing excessive usage included revealed that employees also majorly over used SM for entertainment, boredom avoidance, constant knowledge sharing, and relationship-building.


Subject(s)
Anxiety , Depression , Internet Addiction Disorder , Social Media , Stress, Psychological , Humans , Male , Adult , Female , Cross-Sectional Studies , Depression/psychology , Anxiety/psychology , Social Media/statistics & numerical data , Stress, Psychological/psychology , Internet Addiction Disorder/psychology , Young Adult , Surveys and Questionnaires , Behavior, Addictive/psychology , Middle Aged
2.
Neurosci Lett ; 834: 137844, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38821203

ABSTRACT

Depression is a prevalent global health concern necessitating alternative approaches to conventional antidepressant medications due to its associated adverse effects. Nigella sativa (NS) is recognized for its potential as an antidepressant, offering a promising solution with fewer side effects. This study investigated the antidepressant efficacy of cyclodextrin-complexed lyophilized nanosuspension of NS oleoresin (NSOR) in a murine model of chronic unpredictable mild stress (CUMS)-induced depression. This study sought to evaluate and contrast the antidepressant potential of the nano-NSOR with that of the NS ethanolic extract (NSEE). The prepared nano-NSOR was characterized physicochemically and evaluated for in vitro drug release and in vivo antidepressant activity. The particle size of nano-NSOR was determined to be 164.6 nm. In vitro drug release studies suggested the higher drug release from nano-NSOR (90.15 % after 72 h) compared to the native NSOR (59.55 % after 72 h). Furthermore, nano-NSOR exhibited a more pronounced antidepressant effect than NSEE in the context of CUMS-induced depression. This study highlights a potential alternative for managing depression, addressing the need for improved antidepressant treatments with reduced side effects. These results suggest that nano-NSOR ameliorates CUMS-induced depression by modulating neurotransmitter levels, reducing inflammation, and enhancing neuroprotection.


Subject(s)
Antidepressive Agents , Cyclodextrins , Depression , Nigella sativa , Plant Extracts , Seeds , Stress, Psychological , Animals , Antidepressive Agents/pharmacology , Antidepressive Agents/therapeutic use , Depression/drug therapy , Mice , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Seeds/chemistry , Nigella sativa/chemistry , Stress, Psychological/drug therapy , Male , Cyclodextrins/chemistry , Nanoparticles/chemistry , Freeze Drying , Disease Models, Animal , Suspensions
3.
Diabetol Int ; 15(2): 145-169, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38524936

ABSTRACT

Diabetic nephropathy and peripheral neuropathy are the two main complications of chronic diabetes that contribute to high morbidity and mortality. These conditions are characterized by the dysregulation of multiple molecular signaling pathways and the presence of specific biomarkers such as inflammatory cytokines, indicators of oxidative stress, and components of the renin-angiotensin system. In this review, we systematically collected and collated the relevant information from MEDLINE, EMBASE, ELSEVIER, PUBMED, GOOGLE, WEB OF SCIENCE, and SCOPUS databases. This review was conceived with primary objective of revealing the functions of these biomarkers and signaling pathways in the initiation and progression of diabetic nephropathy and peripheral neuropathy. We also highlighted the potential therapeutic effectiveness of rutin and quercetin, two plant-derived flavonoids known for their antioxidant and anti-inflammatory properties. The findings of our study demonstrated that both flavonoids can regulate important disease-promoting systems, such as inflammation, oxidative stress, and dysregulation of the renin-angiotensin system. Importantly, rutin and quercetin have shown protective benefits against nephropathy and neuropathy in diabetic animal models, suggesting them as potential therapeutic agents. These findings provide a solid foundation for further comprehensive investigations and clinical trials to evaluate the potential of rutin and quercetin in the management of diabetic nephropathy and peripheral neuropathy. This may contribute to the development of more efficient and comprehensive treatment approaches for diabetes-associated complications.

4.
J Pharm Health Care Sci ; 10(1): 7, 2024 Jan 24.
Article in English | MEDLINE | ID: mdl-38268049

ABSTRACT

BACKGROUND: Multidrug-resistant bacterial strains cause several serious infections that can be fatal, such as Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumonia, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacteriaceae (often referred to as ESKAPE pathogens). Since ancient times, several indigenous medical systems in India have utilized diverse medicinal plants (approximately 80,000 species) as conventional treatments for a variety of illnesses. A member of the Fabaceae family, also referred to as "Himalayan indigo," Indigofera heterantha Wall, is well known for its therapeutic properties. METHODS: The present study investigated the antibacterial, antifungal and antihelmintic properties of the roots, bark, leaves, and flowers of I. heterantha from the Kashmir Himalayas. The effectiveness of the extracts against bacteria, fungi, and earthworms. Three of the tested organisms for bacteria were ESKAPE pathogens, as they are responsible for creating fatal bacterial infections. The antifungal potency of I. heterantha aqueous and methanolic extracts was evaluated using the Agar Well Diffusion Assay. The antihelmintic activity was carried out on an adult Pheretima posthuma Indian earth worm, which shares physiological and anatomical similarities with human intestinal roundworm parasites. RESULTS: The methanolic extracts of root and bark have shown prominent activity against all bacterial strains, whereas aqueous extracts of flower, root, and leaves have shown promising activity against Staphylococcus aureus. The aqueous extract demonstrated good activity against S. cerevisiae at a concentration of 200 mg/ml with a zone of inhibition of 16 mm, while the methanolic extract displayed comparable activity against the fungal strains. The remaining two strains, P. crysogenum and A. fumigatus, were only moderately active in response to the extracts. All the extracts have shown anthelmintic activity except aqueous flower. CONCLUSION: These results will pave the way for the bioassay-guided isolation of bioactive constituents that may act as hits for further development as potential antibacterial agents against drug-resistant microbial and helminthic infections.

5.
Exp Physiol ; 109(6): 847-872, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38279951

ABSTRACT

Diabetes mellitus is a chronic disease that is now considered a global epidemic. Chronic diabetes conditions include type 1 and type 2 diabetes, both of which are normally irreversible. As a result of long-term uncontrolled high levels of glucose, diabetes can progress to hyperglycaemic pathologies, such as cardiovascular diseases, retinopathy, nephropathy and neuropathy, among many other complications. The complete mechanism underlying diabetes remains unclear due to its complexity. In this scenario, zebrafish (Danio rerio) have arisen as a versatile and promising animal model due to their good reproducibility, simplicity, and time- and cost-effectiveness. The Zebrafish model allows us to make progress in the investigation and comprehension of the root cause of diabetes, which in turn would aid in the development of pharmacological and surgical approaches for its management. The current review provides valuable reference information on zebrafish models, from the first zebrafish diabetes models using genetic, disease induction and chemical approaches, to the newest ones that further allow for drug screening and testing. This review aims to update our knowledge related to diabetes mellitus by gathering the most authoritative studies on zebrafish as a chemical, dietary and insulin induction, and genetic model for diabetes research.


Subject(s)
Disease Models, Animal , Drug Discovery , Zebrafish , Animals , Drug Discovery/methods , Diabetes Mellitus/drug therapy , Humans , Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/therapeutic use
6.
Behav Brain Res ; 459: 114788, 2024 02 29.
Article in English | MEDLINE | ID: mdl-38036263

ABSTRACT

Does it make a difference what we eat when it comes to our mental health? Food and nutrients are essential not only for human biology and physical appearance but also for mental and emotional well-being. There has been a significant increase in the favourable effects of dietary supplements in the treatment of depressive state in the latest days. Co-supplements which can be a great contribution in the management of depression from the future perspective and might help to reduce standard anti-depressant drug doses, which can be a strategic way to reduce the side effect of standard anti-depressants drugs. This study was designed to evaluate and compare the anti-depressant effects of cholecalciferol-D3 (V.D3), n-3 polyunsaturated fatty acid (PUFA), and a combination of V.D3 + n-3 PUFA with fluoxetine treatment in chronic unpredictable mild stress (CUMS) induced depression in the mice model. We established CUMS depressant mice model and treated CUMS mice with V.D3, n-3 PUFA, and a combination of V.D3 + n-3 PUFA with fluoxetine. Behavioral changes were measured by the forced swim and tail suspension test. Oxidative stress markers and anti-depressant activity were assessed through parameters such as superoxide dismutase, reduced glutathione, lipid peroxidation, and serum corticosterone levels. Additionally, we measured the levels of neurotransmitters dopamine and serotonin. CUMS induced mice displayed depressive-like behaviours. Moreover, cholecalciferol-D3, n-3 PUFA, and a combination of Cholecalciferol-D3 + n-3 PUFA with fluoxetine treatment attenuated the depressive-like behaviour in CUMS mice accompanied with suppression of oxidative stress markers by up-regulated the expression of an antioxidant signalling pathway. The results suggested that treatment of cholecalciferol-D3, n-3 PUFA, and a combination of Cholecalciferol-D3 + n-3 PUFA with fluoxetine significantly ameliorated depressive-like behaviours in CUMS induced depression in mice. To delve further into the implications of these findings, future studies could explore the specific molecular mechanisms underlying the observed effects on oxidative stress markers and the antioxidant signaling pathway. This could provide valuable insights into the potential of dietary supplements in the management of depression and help in reducing the reliance on conventional antidepressant medications, thus improving the overall quality of treatment for this prevalent mental health condition.


Subject(s)
Depression , Fatty Acids, Omega-3 , Mice , Humans , Animals , Depression/drug therapy , Depression/etiology , Depression/metabolism , Fluoxetine/pharmacology , Antioxidants/pharmacology , Antioxidants/metabolism , Cholecalciferol/pharmacology , Cholecalciferol/metabolism , Dietary Supplements , Fatty Acids, Omega-3/pharmacology , Fatty Acids, Omega-3/metabolism , Stress, Psychological/complications , Stress, Psychological/drug therapy , Stress, Psychological/metabolism , Disease Models, Animal , Hippocampus/metabolism , Behavior, Animal
7.
High Blood Press Cardiovasc Prev ; 30(6): 513-531, 2023 Nov.
Article in English | MEDLINE | ID: mdl-38041772

ABSTRACT

Diabetes mellitus, a prevalent global health concern, is characterized by hyperglycemia. However, recent research reveals a more intricate landscape where oxidative stress and endoplasmic reticulum (ER) stress orchestrate a dual assault, profoundly impacting diabetic disorders. This review elucidates the interplay between these two stress pathways and their collective consequences on diabetes. Oxidative stress emanates from mitochondria, where reactive oxygen species (ROS) production spirals out of control, leading to cellular damage. We explore ROS-mediated signaling pathways, which trigger ß-cell dysfunction, insulin resistance, and endothelial dysfunction the quintessential features of diabetes. Simultaneously, ER stress unravels, unveiling how protein folding disturbances activate the unfolded protein response (UPR). We dissect the UPR's dual role, oscillating between cellular adaptation and apoptosis, significantly influencing pancreatic ß-cells and peripheral insulin-sensitive tissues. Crucially, this review exposes the synergy between oxidative and ER stress pathways. ROS-induced UPR activation and ER stress-induced oxidative stress create a detrimental feedback loop, exacerbating diabetic complications. Moreover, we spotlight promising therapeutic strategies that target both stress pathways. Antioxidants, molecular chaperones, and novel pharmacological agents offer potential avenues for diabetes management. As the global diabetes burden escalates, comprehending the dual assault of oxidative and ER stress is paramount. This review not only unveils the intricate molecular mechanisms governing diabetic pathophysiology but also advocates a holistic therapeutic approach. By addressing both stress pathways concurrently, we may forge innovative solutions for diabetic disorders, ultimately alleviating the burden of this pervasive health issue.


Subject(s)
Diabetes Mellitus , Glucose , Humans , Reactive Oxygen Species/metabolism , Endoplasmic Reticulum Stress/physiology , Diabetes Mellitus/diagnosis , Oxidative Stress
8.
Brain Sci ; 13(12)2023 Dec 01.
Article in English | MEDLINE | ID: mdl-38137115

ABSTRACT

Depression is a low-energy condition that has an impact on a person's thoughts, actions, propensities, emotional state, and sense of wellbeing. According to the World Health Organization (WHO), 5% of adults are depressed. Individuals who are depressed are commonly prescribed antidepressants, and sometimes, individuals may have other psychiatric conditions that share overlapping symptoms with depression. These cooccurring conditions can complicate the diagnostic process, leading to a misdiagnosis and the prescription of antidepressants. Capsaicin (CAP) is a known antidepressant. Hence, this study aimed to assess the antidepressant activity of CAP nanoemulsion in nicotine (NC) withdrawal-induced depression in mice. Mice treated with CAP (3 mg/kg) showed reduced immobility in the forced swimming test (FST), tail-suspension test (TST), and open field test (OFT). During the OFT, the animals treated with nanoemulsion (CAP 3 mg/kg) spent less time in the corners than the control animals. Biochemical parameters, such as superoxide dismutase (SOD) and glutathione (GSH), were observed in reduced quantities in the NC withdrawal model (NWM), where they were slightly increased in the high-dose nanoemulsion (CAP 3 mg/kg) compared to the low-dose nanoemulsion (CAP 1 mg/kg). These results suggest that CAP caused antidepressant activity in the NWM via the nanoemulsion.

9.
Biochem Biophys Rep ; 36: 101571, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37965066

ABSTRACT

Stress is a disturbance in homeostasis caused by psychological, physiological, or environmental factors. Prolonged reactions to chronic stress can be detrimental, resulting in various metabolic abnormalities, referred to as metabolic syndrome (MS). There is a reciprocal increased risk between MS and major depressive disorder. Recent studies established an association between inflammation and insulin signaling in type 2 diabetes mellitus with depression. In the present review, we discuss chronic low-grade inflammation, pathways of insulin resistance, and brain glucose metabolism in the context of neuroinflammation and depression. Specific attention is given to psychotropic drugs such as bupropion, mirtazapine, and nefazodone, anti-inflammatory drugs like Celecoxib (COX-2 inhibitor), Etanercept, adalimumab, IL-4Ra antagonist, Anti-IL- 17A antibody (Ixekizumab) and lifestyle modifications including exercise, dietary changes, and sleep hygiene. These therapeutic solutions offer potential in treating depression by targeting metabolic conditions like insulin resistance and inflammatory pathways. The article further explains the significance of a nutrition and antioxidants-rich diet, emphasizing the role of omega-3 fatty acids, vitamin D, zinc, and polyphenols, to improve immunity and activate anti-inflammatory signaling pathways.

10.
Neurosci Lett ; 814: 137441, 2023 09 25.
Article in English | MEDLINE | ID: mdl-37591360

ABSTRACT

In the present study, the objective was to encapsulate piperine in nanoform by solvent evaporation method and to investigate the antidepressant-like activity of nanopiperine in lipopolysaccharide (LPS) induced depression in mice. LPS-induced depression in mice was reversed by repeated treatment of nanopiperine at dosages of 5 and 10 mg/kg body weight for 14 days. After 24 h of LPS injection, the animals were exposed to a (TST) tail suspension test and (FST) forced swim test. A sequence of behaviours was measured on days 0, 7, and 14. On day 14, the animals were euthanized, and the blood was collected; biochemical analysis was performed for the measurement of inflammatory and oxidative stress markers. Within the same period, nanopiperine improved hippocampal progenitor cell proliferation and increased brain-derived neurotrophic factor (BDNF) levels in the hippocampus of mice subjected to LPS-induced stress. In addition, the neurotransmitter estimation by the HPLC method showed that nanopiperine increased the levels of neurotransmitters. In summary, the nanopiperine showed potent neuroprotective and antidepressant activity, and stability relating to the elevated level of hippocampal BDNF level and as compared to pure piperine, the nanopiperine showed better oral bioavailability and stability.


Subject(s)
Depression , Lipopolysaccharides , Mice , Animals , Depression/chemically induced , Depression/drug therapy , Lipopolysaccharides/pharmacology , Brain-Derived Neurotrophic Factor/metabolism , Biological Availability , Antidepressive Agents/pharmacology , Antidepressive Agents/therapeutic use , Hippocampus/metabolism , Disease Models, Animal
11.
Int J Biol Macromol ; 248: 125875, 2023 Sep 01.
Article in English | MEDLINE | ID: mdl-37473899

ABSTRACT

Natural polymers, like chitosan and alginate have potential of appearance, as well as the changes and handling necessary to make it acceptable vehicle for the controlled release of medicines and biomolecules. Microcapsules are characterized as micrometer-sized particulate that can be employed to store chemicals within them. In the present review, we have discussed various advantages, components of microcapsules, release mechanisms, preparation methods, and their applications in drug delivery systems. The preparation methods exhibited strong encapsulation effectiveness and may be used in a wide range of pharmaceutical and biomedical applications. The major advantages of using the microencapsulation technique are, sustained and controlled delivery of drugs, drug targeting, improvement of shelf life, stabilization, immobilization of enzymes and microorganisms. As new biomaterials are developed for the body, they are better suited to the development of pharmaceutical systems than traditional pharmaceuticals because they are more reliable, biocompatible, biodegradable, and nontoxic. Furthermore, the designed microcapsules had been capable of shielding the essential components from hostile environments. More advanced techniques could be developed in the future to facilitate the formulation and applications of microcapsules and working with the pharmaceutical and medical industries.


Subject(s)
Chitosan , Chitosan/chemistry , Capsules/chemistry , Alginates/chemistry , Drug Delivery Systems , Biocompatible Materials/chemistry
12.
Int Immunopharmacol ; 121: 110464, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37390565

ABSTRACT

A chronic auto-immune-mediated disease Psoriasis is associated with manycoexisting or co-occurringconditions, which include a significant risk of malignancies, especiallyskin tumours. Numerous studies were done to understand whether psoriasis itself, comorbidities related to psoriasis, or psoriasis treatment might increase the risk of neoplasms. We reviewed the relation between psoriasis and cancer risk, also the significance of inflammation in cancer The various classes of drugs used to treat psoriasis, including biologics like tumour necrosis factor (TNF) inhibitors; and how they increase cancer risk are deliberated. Literature was collated for the past five years from the data bases like PubMed, Medline, Google Scholar, etc. Literatures discussing the skin cancer linked to psoriasis were reviewed. Possible mechanisms associated between inflammation and psoriasis; skin cancer was explained in the context of the several psoriasis medications that increase the likelihood of skin cancer. The risk of cancer in other cutaneous auto-inflammatory diseases is also elucidated. It is frequently observed that increased doses of PUVA therapy, immunosuppressive medications, and lifestyle changes alter the aetiology of the tumours. This review is conceptualized to shed the light on probable mechanisms involved in these connections as well as the chance of cancer in psoriasis patients.


Subject(s)
Psoriasis , Skin Neoplasms , Humans , Psoriasis/drug therapy , Skin Neoplasms/etiology , Skin/pathology , Comorbidity , Inflammation/complications
13.
J Pers Med ; 13(3)2023 Mar 15.
Article in English | MEDLINE | ID: mdl-36983706

ABSTRACT

The goal of this research is to study the prevalence of cognitive impairment in diabetes mellitus (DM) patients and establish the necessity of detecting and treating it early in these patients. A cross-sectional study was conducted at a tertiary care hospital in Mysuru for 4 months examined diabetic patients (test) and nondiabetic subjects (control) for cognitive decline using the Montreal Cognitive Assessment (MoCA) tool. Cognitive functions such as visuospatial/executive function, naming, attention, language, abstraction, delayed recall, and orientation were assessed in both groups. The diabetic group showed a significantly lower total MoCA score than the non-diabetic group (18.99 ± 0.48 and 26.21 ± 0.46, respectively; p < 0.001). Assessment of scores in diabetic patients demonstrated the significant influence of age demographics on cognitive impairment (p-value < 0.001). Furthermore, a higher proportion of diabetic patients displayed cognitive impairment despite a higher score in a single subdomain, making it evident that diabetes is diverse and multifactorial in origin, where oxidative stress and inflammatory responses play a predominant role. This study suggested that the local T2DM population residing in Mysuru (India) has a high prevalence of cognitive impairment, evident from poor performance in almost all cognitive domains assessed by MoCA. Future studies could examine the generalizability of cognitive function findings in diabetic patients across diverse geographic regions and ethnic groups, as well as investigate interventions such as lifestyle modifications and medication to prevent or delay cognitive decline in those with diabetes.

14.
J Pers Med ; 13(2)2023 Jan 27.
Article in English | MEDLINE | ID: mdl-36836458

ABSTRACT

Depression is a common mood disorder characterized by persistent sadness and loss of interest. Research suggests an association between the inclusion of omega-3 fatty acids in the diet and a reduced risk for depression. The present study evaluated the effectiveness of omega-3 fatty acid supplements in alleviating depressive symptoms in patients with mild to moderate depression. A total of 165 patients suffering from mild to moderated depression were randomized to receive omega-3 fatty acid supplementation, an antidepressant (single agent), or a combination of an antidepressant and omega-3 fatty acid supplementation. The clinical features of depression were assessed using the Hamilton Depression Rating Scale (HDRS) during the follow-up period. A statistically significant improvement in depressive symptoms was observed from baseline to first, second and third follow-ups within each treatment arm as measured by HRDS scores (p = 0.00001). Further, the HDRS scores at the third follow-up were significantly lower in patients on combination therapy of omega-3 fatty acid supplement and antidepressants (arm-3) than the patients on the omega-3 fatty acid supplement alone (arm-1) [Q = 5.89; p = 0.0001] or the patients taking an antidepressant alone (arm 2) [Q = 4.36; p = 0.0068]. The combination of an omega-3 fatty acid supplement and an antidepressant elicited significantly higher improvement in depressive symptoms than the supplement or the antidepressant alone.

15.
Healthcare (Basel) ; 10(10)2022 Oct 19.
Article in English | MEDLINE | ID: mdl-36292530

ABSTRACT

Depression is a prevalent mental health condition treated with antidepressants and other psychotropic medications. This study aimed to assess the utilization pattern of antidepressants among patients visiting the outpatient clinic of the psychiatry department of a tertiary care hospital. The study included the patients who visited the study site and fulfilled the mental and behavioral diagnostic criteria for depression. The demographic and clinical details, including drugs prescribed, were documented in a study-specific data collection form. The ratio of Prescribed Daily Dose to Defined Daily Dose (PDD: DDD) was calculated to assess the adequacy of antidepressant utilization. Data total of 154 patients were collected. A total of 22 psychotropic drugs were used among the study patients as mono (n = 70), dual (n = 69), triple (n = 10), or quadruple therapy (n = 1). Escitalopram was the most often prescribed antidepressant out of the nine antidepressants alone and in combination and was used in slightly high doses (PDD: DDD ratio 1.6). Sertraline, paroxetine, and desvenlafaxine, were used in adequate doses (PDD: DDD between 1 and 1.1), and fluoxetine, duloxetine, amitriptyline, imipramine, and mirtazapine, were used in inadequate doses (PDD: DDD <0.5). Our study findings reveal the need for continuous assessment of antidepressants medications usage in a hospital set up.

16.
3 Biotech ; 12(9): 230, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35992895

ABSTRACT

Organelle crosstalk is significant in regulating their respective functions and subsequent cell fate. Mitochondria and lysosomes are amongst the essential organelles in maintaining cellular homeostasis. Mitochondria-lysosome connections, which may develop dynamically in the human neurons, have been identified as sites of bidirectional communication. Aberrancies are often associated with neurodegenerative disorders like Parkinson's disease (PD), suggesting the physical and functional link between these two organelles. PD is often linked with genetic mutations of several mutations discovered in the familial forms of the disease; some are considered risk factors. Many of these genes are either associated with mitochondrial function or belong to endo-lysosomal pathways. The recent investigations have indicated that neurons with mutant glucosylceramidase beta (GBA1) exhibit extended mitochondria-lysosome connections in individuals with PD. This may be due to impaired control of the untethering protein, which aids in the hydrolysis of Rab7 GTP required for contact untethering. A GCase modulator may be used to augment the reduced GBA1 lysosomal enzyme activity in the neurons of PD patients. This review focuses on how GBA1 mutation in PD is interlinked with mitochondria-lysosome (ML) crosstalk, exploring the pathways governing these interactions and mechanistically comprehending the mitochondrial and lysosomal miscommunication in the pathophysiology of PD. This review is based on the limited literature available on the topic and hence may be subject to bias in its views. Our estimates may be conservative and limited due to the lack of studies under the said discipline due to its inherent complex nature. The current association of GBA1 to PD pathogenesis is based on the limited scope of study and further research is necessary to explore the risk factors further and identify the relationship with more detail.

17.
Eur J Pharmacol ; 908: 174376, 2021 Oct 05.
Article in English | MEDLINE | ID: mdl-34303667

ABSTRACT

Cholelithiasis is a common and frequent condition all over the world with a high prevalence rate in western countries. Individuals with cholesterol gallstone disease experience intense gastrointestinal symptoms and have a high risk of developing comorbidities like cholecystitis, Gall bladder (GB) cancer and pancreatitis. Multiple risk factors associated with cholesterol gallstones include but not limited to genetics, dietary habits, lifestyle changes, comorbid conditions and various drugs. These factors may lead to alteration in bile, cholesterol & phospholipids homeostasis in the GB, intestine and hepatocytes culminating in cholesterol gallstones formation. Surgical (cholecystectomy) and non-surgical (oral dissolution therapy) treatments are available for the disease, albeit with certain complications and high treatment cost. Thus, there is a need for interventions, complementary or alternative therapies for the treatment and prevention of cholesterol gallstones. Currently available drug therapies used for cholesterol gallstones include statins and ezetimibe. Many patients consider traditional herbal practitioners due to their promise of non-invasive and pain free management of gall stones. This present a positive shift towards generally acceptable safety and cost effectiveness of herbal treatment warranting extensive research for alternative or complementary choice such as herbal plants as an emerging area for their potential therapeutic effects. This review discusses current strategies, latest trends available in the disease pathogenesis, drug development for novel targets, risk management, newer anti-lithogenic drugs and herbal plants that target the different aspects of the disease.


Subject(s)
Gallstones , Bile , Cholesterol , Ezetimibe , Risk Factors
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