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1.
Afr J Reprod Health ; 28(6): 66-74, 2024 06 30.
Article in English | MEDLINE | ID: mdl-38979874

ABSTRACT

Dysmenorrhea, the most common gynecological pain syndrome reported in women, is understudied in refugee communities. In addition, the association between dysmenorrhea self-medication and mental health symptoms in this population is poorly understood. We aimed to examine whether the use of dysmenorrhea analgesic self-medications and other clinical factors are associated with post-traumatic stress disorder (PTSD), depression, anxiety and insomnia severity in female war refugees residing in Zaatari Camp. This study followed a cross-sectional design and was performed on a cohort of women with predefined inclusion criteria. The severity of PTSD, depression, anxiety and insomnia were assessed using Davidson Trauma Scale, the Patient Health Questionnaire-9, the General Anxiety Disorder-7, and the Arabic version of the Insomnia Severity Index, respectively. Data were analysed from 386 participants. Using OTC paracetamol was significantly associated with higher PTSD severity (B=4.16, t= 2.43, p=0.01), and severe depression (OR=1.88, 95% CI= 1.07-3.28, p=0.03), while OTC non-steroidal anti-inflammatory drugs (NSAIDs) was significantly associated with severe insomnia (OR=1.62, 95% CI= 1.05-2.49, p= 0.02). In conclusion, self-medication with analgesics was correlated with poor mental health; close medical and psychiatric follow-up are required to supervise pain self-medication and implement non-pharmacological strategies to manage dysmenorrhea in this fragile community.


La dysménorrhée, le syndrome douloureux gynécologique le plus fréquemment signalé chez les femmes, est peu étudiée dans les communautés de réfugiés. De plus, l'association entre l'automédication de la dysménorrhée et les symptômes de santé mentale dans cette population est mal comprise. Nous avions pour objectif d'examiner si l'utilisation d'automédicaments analgésiques contre la dysménorrhée et d'autres facteurs cliniques sont associés au trouble de stress post-traumatique (SSPT), à la dépression, à l'anxiété et à la gravité de l'insomnie chez les réfugiées de guerre résidant dans le camp de Zaatari. Cette étude a suivi une conception transversale et a été réalisée sur une cohorte de femmes avec des critères d'inclusion prédéfinis. La gravité du SSPT, de la dépression, de l'anxiété et de l'insomnie a été évaluée à l'aide de l'échelle de traumatisme de Davidson, du questionnaire sur la santé du patient-9, du trouble d'anxiété général-7 et de la version arabe de l'indice de gravité de l'insomnie, respectivement. Les données ont été analysées auprès de 386 participants. L'utilisation de paracétamol en vente libre était significativement associée à une gravité plus élevée du SSPT (B = 4,16, t = 2,43, p = 0,01) et à une dépression sévère (OR = 1,88, IC à 95 % = 1,07-3,28, p = 0,03), tandis que les médicaments non stéroïdiens en vente libre les anti-inflammatoires (AINS) étaient associés de manière significative à l'insomnie sévère (OR = 1,62, IC à 95 % = 1,05-2,49, p = 0,02). En conclusion, l'automédication avec des analgésiques était corrélée à une mauvaise santé mentale ; un suivi médical et psychiatrique étroit est nécessaire pour encadrer l'automédication de la douleur et mettre en œuvre des stratégies non pharmacologiques pour prendre en charge la dysménorrhée dans cette communauté fragile.


Subject(s)
Refugees , Self Medication , Humans , Female , Refugees/psychology , Adult , Dysmenorrhea/psychology , Mental Health , Young Adult , Refugee Camps
2.
Inflammation ; 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38918333

ABSTRACT

This study aimed to investigate the therapeutic potential of scopoletin in ulcerative colitis, with a primary focus on its impact on crucial inflammatory pathways and immune responses. A male mouse model of DSS-induced colitis was employed with six distinct groups: a control group, a group subjected to DSS only, three groups treated with varying scopoletin doses, and the final group treated with dexamethasone. The investigation included an assessment of the effects of scopoletin on colitis symptoms, including alterations in body weight, Disease Activity Index (DAI), and histopathological changes in colonic tissue. Furthermore, this study scrutinized the influence of scopoletin on cytokine production, PPARγ and NF-κB expression, NLRP3 inflammasome, and the composition of intestinal bacteria. Scopoletin treatment yielded noteworthy improvements in DSS-induced colitis in mice, as evidenced by reduced weight loss and colonic shortening (p < 0.05, < 0.01, respectively). It effectively diminished TNF-α, IL-1ß, and IL-12 cytokine levels (p < 0.01, p < 0.05), attenuated NLRP3 inflammasome activation and the associated cytokine release (p < 0.05, p < 0.01), and modulated the immune response by elevating PPARγ expression while suppressing NF-κB pathway activation (p < 0.05, p < 0.01). Additionally, scopoletin induced alterations in the gut microbiota composition, augmenting beneficial Lactobacillus and Bifidobacteria while reducing E. coli (p < 0.05). It also enhanced tight junction proteins, signifying an improvement in the intestinal barrier integrity (p < 0.05, < 0.01). Scopoletin is a promising therapeutic agent for managing ulcerative colitis, showing benefits that extend beyond mere anti-inflammatory actions to encompass regulatory effects on gut microbiota and restoration of intestinal integrity.

3.
Cancers (Basel) ; 16(11)2024 May 27.
Article in English | MEDLINE | ID: mdl-38893150

ABSTRACT

Immunotherapy is a rapidly advancing field of research in the treatment of conditions such as cancer and autoimmunity. Nanomaterials can be designed for immune system manipulation, with precise targeted delivery and improved immunomodulatory efficacy. Here, we elaborate on various strategies using nanomaterials, including liposomes, polymers, and inorganic NPs, and discuss their detailed design intricacies, mechanisms, and applications, including the current regulatory issues. This type of nanomaterial design for targeting specific immune cells or tissues and controlling release kinetics could push current technological frontiers and provide new and innovative solutions for immune-related disorders and diseases without off-target effects. These materials enable targeted interactions with immune cells, thereby enhancing the effectiveness of checkpoint inhibitors, cancer vaccines, and adoptive cell therapies. Moreover, they allow for fine-tuning of immune responses while minimizing side effects. At the intersection of nanotechnology and immunology, nanomaterial-based platforms have immense potential to revolutionize patient-centered immunotherapy and reshape disease management. By prioritizing safety, customization, and compliance with regulatory standards, these systems can make significant contributions to precision medicine, thereby significantly impacting the healthcare landscape.

4.
Cell Mol Life Sci ; 81(1): 214, 2024 May 11.
Article in English | MEDLINE | ID: mdl-38733529

ABSTRACT

The non-coding RNAs comprise a large part of human genome lack of capacity in encoding functional proteins. Among various members of non-coding RNAs, the circular RNAs (circRNAs) have been of importance in the pathogenesis of human diseases, especially cancer. The circRNAs have a unique closed loop structure and due to their stability, they are potential diagnostic and prognostic factors in cancer. The increasing evidences have highlighted the role of circRNAs in the modulation of proliferation and metastasis of cancer cells. On the other hand, metastasis has been responsible for up to 90% of cancer-related deaths in patients, requiring more investigation regarding the underlying mechanisms modulating this mechanism. EMT enhances metastasis and invasion of tumor cells, and can trigger resistance to therapy. The cells demonstrate dynamic changes during EMT including transformation from epithelial phenotype into mesenchymal phenotype and increase in N-cadherin and vimentin levels. The process of EMT is reversible and its reprogramming can disrupt the progression of tumor cells. The aim of current review is to understanding the interaction of circRNAs and EMT in human cancers and such interaction is beyond the regulation of cancer metastasis and can affect the response of tumor cells to chemotherapy and radiotherapy. The onco-suppressor circRNAs inhibit EMT, while the tumor-promoting circRNAs mediate EMT for acceleration of carcinogenesis. Moreover, the EMT-inducing transcription factors can be controlled by circRNAs in different human tumors.


Subject(s)
Carcinogenesis , Drug Resistance, Neoplasm , Epithelial-Mesenchymal Transition , Neoplasm Metastasis , Neoplasms , RNA, Circular , Humans , RNA, Circular/genetics , RNA, Circular/metabolism , Epithelial-Mesenchymal Transition/genetics , Neoplasms/genetics , Neoplasms/pathology , Neoplasms/metabolism , Carcinogenesis/genetics , Carcinogenesis/pathology , Drug Resistance, Neoplasm/genetics , Cell Plasticity/genetics , Animals , Gene Expression Regulation, Neoplastic
5.
Int J Psychiatry Med ; : 912174241255420, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38771967

ABSTRACT

OBJECTIVE: This study investigated the prevalence and correlates of fibromyalgia and insomnia in a sample of Women with Multiple Sclerosis (WMS). METHODS: The study was cross-sectional in design and recruited a sample of 163 women with Relapsing-Remitting Multiple Sclerosis (RRMS). Fibromyalgia was assessed using the Patient Self-Report Survey (PSRS), following criteria outlined by the American College of Rheumatology. Insomnia was measured using the Arabic version of the Insomnia Severity Index (ISI-A). RESULTS: The prevalence of fibromyalgia and insomnia was 28.2% (n = 46) and 46.3% (n = 76), respectively. Multivariate analyses were used to determine significant independent correlates. Fibromyalgia was associated with age above 40 years (OR = 2.29, 95% CI = 1.01-5.18, P = .04), high school education (OR = 3.69, 95% CI = 1.62-8.37, P = .002), and non-use of analgesics (OR = .02, 95% CI = .004-.21, P = .001). Insomnia symptoms were significantly associated only with age above 40 years (OR = 2.16, 95% CI = 1.16-4.04, P = .01). CONCLUSION: These findings highlight the need for increased attention by primary care physicians towards diagnosing and treating fibromyalgia and insomnia among women with RRMS in Jordan, particularly among older women.

6.
AIMS Public Health ; 11(1): 209-222, 2024.
Article in English | MEDLINE | ID: mdl-38617411

ABSTRACT

Background: Dysmenorrhea is wide spread gynecological disorder among that affect the quality of life of women world wide. The current study aims to examine whether war displacement, mental health symptoms, and other clinical factors are associated with dysmenorrhea severity. Methods: This is a cross-sectional case-control study recruiting two groups: displaced Syrian women and un-displaced local Jordanian women. Demographics and clinical details were recorded. The severity of dysmenorrhea was assessed using WaLIDD scale, the PHQ-9 scale was emplyed to assess depressive symptoms, anxiety was assessed using the GAD-7 scale, and insomnia was assessed using the ISI-A scale. Predictors of severe dysmenorrhea in females using multivariate binary logistic regression. Results: Out of 808 of the total participants, 396 (49%) were Syrian displaced war refugees, 424 (42.5%) reported using paracetamol, 232 (23.2%) were using NSAIDs, and 257 (25.9%) using herbal remedies. Severe dysmenorrhea was associated with war displacement (OR = 2.14, 95% CI = 1.49-3.08, p < 0.001), not using NSAIDs (OR = 2.75, 95% CI = 1.91-3.95, p < 0.001), not using herbal remedies (OR = 2.01, 95% CI = 1.13-3.60, p = 0.01), depression (OR = 2.14, 95% CI = 1.40-3.29, p < 0.001), and insomnia (OR = 1.66, 95% CI = 1.14-2.42, p = 0.009). Conclusions: War displacement, type of analgesic, depression, and insomnia are risk factors for severe dysmenorrhea.

7.
Expert Opin Drug Deliv ; 21(3): 399-422, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38623735

ABSTRACT

INTRODUCTION: Doxorubicin (DOX) emerges as a cornerstone in the arsenal of potent chemotherapeutic agents. Yet, the clinical deployment of DOX is tarnished by its proclivity to induce severe cardiotoxic effects, culminating in heart failure and other consequential morbidities. In response, a panoply of strategies has undergone rigorous exploration over recent decades, all aimed at attenuating DOX's cardiotoxic impact. The advent of encapsulating DOX within lipidic or polymeric nanocarriers has yielded a dual triumph, augmenting DOX's therapeutic efficacy while mitigating its deleterious side effects. AREAS COVERED: Recent strides have spotlighted the emergence of DOX conjugates as particularly auspicious avenues for ameliorating DOX-induced cardiotoxicity. These conjugates entail the fusion of DOX through physical or chemical bonds with diminutive natural or synthetic moieties, polymers, biomolecules, and nanoparticles. This spectrum encompasses interventions that impinge upon DOX's cardiotoxic mechanism, modulate cellular uptake and localization, confer antioxidative properties, or refine cellular targeting. EXPERT OPINION: The endorsement of DOX conjugates as a compelling stratagem to mitigate DOX-induced cardiotoxicity resounds from this exegesis, amplifying safety margins and the therapeutic profile of this venerated chemotherapeutic agent. Within this ambit, DOX conjugates stand as a beacon of promise in the perpetual pursuit of refining chemotherapy-induced cardiac compromise.


Subject(s)
Antibiotics, Antineoplastic , Cardiotoxicity , Doxorubicin , Drug Carriers , Nanoparticles , Doxorubicin/adverse effects , Doxorubicin/administration & dosage , Cardiotoxicity/prevention & control , Cardiotoxicity/etiology , Humans , Animals , Antibiotics, Antineoplastic/adverse effects , Antibiotics, Antineoplastic/administration & dosage , Antibiotics, Antineoplastic/chemistry , Drug Carriers/chemistry , Nanoparticles/chemistry , Drug Delivery Systems , Polymers/chemistry , Heart Failure/drug therapy , Heart Failure/chemically induced , Lipids/chemistry
8.
Pathol Res Pract ; 257: 155285, 2024 May.
Article in English | MEDLINE | ID: mdl-38653089

ABSTRACT

Glioblastoma, a highly lethal form of brain cancer, is characterized by its aggressive growth and resistance to conventional treatments, often resulting in limited survival. The response to therapy is notably influenced by various patient-specific genetic factors, underscoring the disease's complexity. Despite the utilization of diverse treatment modalities such as surgery, radiation, and chemotherapy, many patients experience local relapse, emphasizing the critical need for improved therapeutic strategies to effectively target these formidable tumors. Recent years have witnessed a surge in interest in natural products derived from plants, particularly alkaloids, for their potential anticancer effects. Alkaloids have shown promise in cancer chemotherapy by selectively targeting crucial signaling pathways implicated in tumor progression and survival. Specifically, they modulate the NF-κB and MAPK pathways, resulting in reduced tumor growth and altered gene expression across various cancer types. Additionally, alkaloids exhibit the capacity to induce cell cycle arrest, further impeding tumor proliferation in several malignancies. This review aims to delineate recent advances in understanding the pathology of glioblastoma multiforme (GBM) and to explore the potential therapeutic implications of alkaloids in managing this deadly disease. By segregating discussions on GBM pathology from those on alkaloid-based therapies, we provide a structured overview of the current challenges in GBM treatment and the promising opportunities presented by alkaloid-based interventions. Furthermore, we briefly discuss potential future directions in GBM research and therapy beyond alkaloids, including emerging treatment modalities or areas of investigation that hold promise for improving patient outcomes. In conclusion, our efforts offer hope for enhanced outcomes and improved quality of life for GBM patients through alkaloid-based therapies. By integrating insights from pathology and therapeutic perspectives, we underscore the significance of a comprehensive approach in addressing this devastating disease.


Subject(s)
Brain Neoplasms , Glioblastoma , Humans , Glioblastoma/pathology , Glioblastoma/therapy , Glioblastoma/genetics , Brain Neoplasms/therapy , Brain Neoplasms/pathology , Brain Neoplasms/genetics , Alkaloids/therapeutic use , Signal Transduction/drug effects , Animals
9.
J Clin Med ; 13(6)2024 Mar 14.
Article in English | MEDLINE | ID: mdl-38541907

ABSTRACT

(1) Background: Attention Deficit Hyperactivity Disorder (ADHD)-like symptoms and insomnia are closely related. The present study examined whether the use of different sleep aids was related to severe ADHD-like symptoms in Jordanian adults screened for insomnia. (2) Methods: This cross-sectional study used predefined inclusion criteria. The severity of ADHD was assessed using the validated Arabic version of the Adult ADHD Self-Report Scale. (3) Results: Data were analyzed from 244 subjects who met the inclusion criteria for severe insomnia, of which 147 (65.3%) reported not using any sleep aid, 50 (22.3%) reported using homeopathy remedies as sleep aids, and 41 (18.3%) reported using over-the-counter antihistamines as sleep aids. Regression analysis revealed that the use of such sleep aids-namely, "homeopathy herbal remedies" and "over-the-counter antihistamines"-was not associated (p > 0.05) with ADHD-like symptoms. However, "age above 31 years old" was significantly associated (B = -3.95, t = -2.32, p = 0.002) with lower ADHD severity, while the "diagnosis with chronic diseases" was significantly associated (B = 4.15, t = 1.99, p = 0.04) with higher ADHD severity. (4) Conclusions: Sleep aids are not associated with ADHD-like symptoms in adults. More research is required to uncover the risk factors for adult ADHD, especially insomnia.

10.
Int J Mol Sci ; 25(4)2024 Feb 06.
Article in English | MEDLINE | ID: mdl-38396638

ABSTRACT

The study of intercellular adhesion molecule-1 (ICAM-1) and SIRT1, a member of the sirtuin family with nitric oxide (NO), is emerging in depression and anxiety. As with all antidepressants, the efficacy is delayed and inconsistent. Ascorbic acid (AA) and vitamin D (D) showed antidepressant properties, while etifoxine (Etx), a GABAA agonist, alleviates anxiety symptoms. The present study aimed to investigate the potential augmentation of citalopram using AA, D and Etx and related the antidepressant effect to brain and serum ICAM-1, SIRT1 and NO in an animal model. BALB/c mice were divided into naive, control, citalopram, citalopram + etx, citalopram + AA, citalopram + D and citalopram + etx + AA + D for 7 days. On the 8th day, the mice were restrained for 8 h, followed by a forced swim test and marble burying test before scarification. Whole-brain and serum expression of ICAM-1, Sirt1 and NO were determined. Citalopram's antidepressant and sedative effects were potentiated by ascorbic acid, vitamin D and etifoxine alone and in combination (p < 0.05), as shown by the decreased floating time and rearing frequency. Brain NO increased significantly (p < 0.05) in depression and anxiety and was associated with an ICAM-1 increase versus naive (p < 0.05) and a Sirt1 decrease (p < 0.05) versus naive. Both ICAM-1 and Sirt1 were modulated by antidepressants through a non-NO-dependent pathway. Serum NO expression was unrelated to serum ICAM-1 and Sirt1. Brain ICAM-1, Sirt1 and NO are implicated in depression and are modulated by antidepressants.


Subject(s)
Anxiety , Citalopram , Depression , Nitric Oxide , Oxazines , Animals , Mice , Antidepressive Agents/pharmacology , Antidepressive Agents/therapeutic use , Anxiety/drug therapy , Ascorbic Acid/pharmacology , Ascorbic Acid/therapeutic use , Citalopram/pharmacology , Citalopram/therapeutic use , Depression/drug therapy , Intercellular Adhesion Molecule-1 , Oxazines/pharmacology , Oxazines/therapeutic use , Sirtuin 1 , Vitamin D/pharmacology , Vitamin D/therapeutic use , Vitamins , Drug Therapy, Combination
11.
EXCLI J ; 23: 62-78, 2024.
Article in English | MEDLINE | ID: mdl-38357097

ABSTRACT

Addressing the formidable challenge posed by the development of effective and personalized interventions for major depressive disorder (MDD) necessitates a comprehensive comprehension of the intricate role that plasma amino acids play and their implications in MDD pathology and pharmacology. Amino acids, owing to their indispensable functions in neurotransmission, metabolism, and immune regulation, emerge as pivotal entities in this intricate disorder. Our primary objective entails unraveling the underlying mechanisms and unveiling tailored treatments through a meticulous investigation into the interplay between plasma amino acids, MDD, and pharmacological strategies. By conducting a thorough and exhaustive review of the existing literature, we have identified pertinent studies on plasma amino acids in MDD, thereby uncovering noteworthy disturbances in the profiles of amino acids among individuals afflicted by MDD when compared to their healthy counterparts. Specifically, disruptions in the metabolism of tryptophan, phenylalanine, and tyrosine, which serve as precursors to essential neurotransmitters, have emerged as prospective biomarkers and critical contributors to the pathophysiology of depression. Amnio acids play an essential role in MDD and could represent an attractive pharmacological target, more studies are further required to fully reveal their underlying mechanisms.

12.
Rheumatol Int ; 44(4): 715-723, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38285107

ABSTRACT

Suboptimal fibromyalgia management with over-the-counter analgesics leads to deteriorated outcomes for pain and mental health symptoms especially in low-income countries hosting refugees. To examine the association between the over-the-counter analgesics and the severity of fibromyalgia, depression, anxiety and PTSD symptoms in a cohort of Syrian refugees. This is a cross-sectional study. Fibromyalgia was assessed using the patient self-report survey for the assessment of fibromyalgia. Depression was measured using the Patient Health Questionnaire-9, insomnia severity was measured using the insomnia severity index (ISI-A), and PTSD was assessed using the Davidson trauma scale (DTS)-DSM-IV. Data were analyzed from 291. Among them, 221 (75.9%) reported using acetaminophen, 79 (27.1%) reported using non-steroidal anti-inflammatory drugs (NSAIDs), and 56 (19.2%) reported receiving a prescription for centrally acting medications (CAMs). Fibromyalgia screening was significantly associated with using NSAIDs (OR 3.03, 95% CI 1.58-5.80, p = 0.001). Severe depression was significantly associated with using NSAIDs (OR 2.07, 95% CI 2.18-3.81, p = 0.02) and CAMs (OR 2.74, 95% CI 1.30-5.76, p = 0.008). Severe insomnia was significantly associated with the use of CAMs (OR 3.90, 95% CI 2.04-5.61, p < 0.001). PTSD symptoms were associated with the use of CAMs (ß = 8.99, p = 0.001) and NSAIDs (ß = 10.39, p < 0.001). Improper analgesics are associated with poor fibromyalgia and mental health outcomes, prompt awareness efforts are required to address this challenge for the refugees and health care providers.


Subject(s)
Fibromyalgia , Refugees , Sleep Initiation and Maintenance Disorders , Stress Disorders, Post-Traumatic , Humans , Female , Mental Health , Cross-Sectional Studies , Stress Disorders, Post-Traumatic/drug therapy , Fibromyalgia/diagnosis , Fibromyalgia/drug therapy , Syria , Depression/drug therapy , Analgesics/adverse effects , Anti-Inflammatory Agents, Non-Steroidal , Internet
13.
Cell Signal ; 116: 111043, 2024 04.
Article in English | MEDLINE | ID: mdl-38211841

ABSTRACT

Calcium is a ubiquitous second messenger that is indispensable in regulating neurotransmission and memory formation. A precise intracellular calcium level is achieved through the concerted action of calcium channels, and calcium exerts its effect by binding to an array of calcium-binding proteins, including calmodulin (CAM), calcium-calmodulin complex-dependent protein kinase-II (CAMK-II), calbindin (CAL), and calcineurin (CAN). Calbindin orchestrates a plethora of signaling events that regulate synaptic transmission and depolarizing signals. Vitamin D, an endogenous fat-soluble metabolite, is synthesized in the skin upon exposure to ultraviolet B radiation. It modulates calcium signaling by increasing the expression of the calcium-sensing receptor (CaSR), stimulating phospholipase C activity, and regulating the expression of calcium channels such as TRPV6. Vitamin D also modulates the activity of calcium-binding proteins, including CAM and calbindin, and increases their expression. Calbindin, a high-affinity calcium-binding protein, is involved in calcium buffering and transport in neurons. It has been shown to inhibit apoptosis and caspase-3 activity stimulated by presenilin 1 and 2 in AD. Whereas CAM, another calcium-binding protein, is implicated in regulating neurotransmitter release and memory formation by phosphorylating CAN, CAMK-II, and other calcium-regulated proteins. CAMK-II and CAN regulate actin-induced spine shape changes, which are further modulated by CAM. Low levels of both calbindin and vitamin D are attributed to the pathology of Alzheimer's disease. Further research on vitamin D via calbindin-CAMK-II signaling may provide newer insights, revealing novel therapeutic targets and strategies for treatment.


Subject(s)
Alzheimer Disease , Vitamin D , Humans , Calcium Signaling , Calbindins , Calmodulin , Calcium , Calcium-Binding Proteins , Calcium Channels , Calcineurin , Calcium-Calmodulin-Dependent Protein Kinase Type 2
14.
Inflammopharmacology ; 32(2): 1147-1157, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38180676

ABSTRACT

Depression is linked with oxidative stress and inflammation, where key players include nitric oxide (NO), nuclear factor erythroid 2-related factor 2 (Nrf2), Brain-Derived Neurotrophic Factor (BDNF), and Heme Oxidase-1 (HO-1). Augmenting the efficacy of antidepressants represents a compelling avenue of exploration. We explored the potential of vitamins C and D as adjuncts to escitalopram (Esc) in a lipopolysaccharide (LPS)-induced depression model focusing on the aforementioned biomarkers. Male Swiss albino mice were stratified into distinct groups: control, LPS, LPS + Esc, LPS + Esc + Vit C, LPS + Esc + Vit D, and LPS + Esc + Vit C + Vit D. After a 7-day treatment period, a single LPS dose (2 mg/kg), was administered, followed by comprehensive assessments of behavior and biochemical parameters. Notably, a statistically significant (p < 0.05) alleviation of depressive symptoms was discerned in the Esc + Vit C + Vit D group versus the LPS group, albeit with concomitant pronounced sedation evident in all LPS-treated groups (p < 0.05). Within the cortex, LPS reduced (p < 0.05) the expression levels of NOx, Nrf2, BDNF, and HO-1, with only HO-1 being reinstated to baseline in the LPS + Esc + Vit D and the LPS + Esc + Vit C + Vit D groups. Conversely, the hippocampal NOx, Nrf2, and HO-1 levels remained unaltered following LPS administration. Notably, the combination of Esc, Vit C, and Vit D effectively restored hippocampal BDNF levels, which had been diminished by Esc alone. In conclusion, vitamins C and D enhance the therapeutic effects of escitalopram through a mechanism independent of Nrf2. These findings underscore the imperative need for in-depth investigations.


Subject(s)
Escitalopram , Lipopolysaccharides , Mice , Animals , Male , Lipopolysaccharides/pharmacology , Depression/drug therapy , Depression/metabolism , Ascorbic Acid/pharmacology , Brain-Derived Neurotrophic Factor/metabolism , NF-E2-Related Factor 2/metabolism , Vitamins , Adjuvants, Immunologic , Vitamin D , Models, Animal
15.
Gene ; 905: 148174, 2024 May 05.
Article in English | MEDLINE | ID: mdl-38242374

ABSTRACT

The intersection of mathematical modeling, nanotechnology, and epidemiology marks a paradigm shift in our battle against infectious diseases, aligning with the focus of the journal on the regulation, expression, function, and evolution of genes in diverse biological contexts. This exploration navigates the intricate dance of viral transmission dynamics, highlighting mathematical models as dual tools of insight and precision instruments, a theme relevant to the diverse sections of Gene. In the context of virology, ethical considerations loom large, necessitating robust frameworks to protect individual rights, an aspect essential in infectious disease research. Global collaboration emerges as a critical pillar in our response to emerging infectious diseases, fortified by the predictive prowess of mathematical models enriched by nanotechnology. The synergy of interdisciplinary collaboration, training the next generation to bridge mathematical rigor, biology, and epidemiology, promises accelerated discoveries and robust models that account for real-world complexities, fostering innovation and exploration in the field. In this intricate review, mathematical modeling in viral transmission dynamics and epidemiology serves as a guiding beacon, illuminating the path toward precision interventions, global preparedness, and the collective endeavor to safeguard human health, resonating with the aim of advancing knowledge in gene regulation and expression.


Subject(s)
Communicable Diseases , Humans , Communicable Diseases/epidemiology , Models, Theoretical , Mathematics
16.
Int J Pharm ; 650: 123678, 2024 Jan 25.
Article in English | MEDLINE | ID: mdl-38065344

ABSTRACT

The primary objective of this study was to enhance the effectiveness of the protease inhibitor antiretroviral drug by designing a novel delivery system using carboxylated multiwalled carbon nanotubes (COOH-MWCNTs). To achieve this, Fosamprenavir calcium (FPV), a prodrug of amprenavir known for inhibiting the proteolytic cleavage of immature virions, was selected as the protease inhibitor antiretroviral drug, and loaded onto COOH-MWCNTs using a direct loading method. The structural specificity of the drug-loaded MWCNTs, the percent entrapment efficiency, and in vitro drug release were rigorously evaluated for the developed formulation, referred to as FPV-MWCNT. Fourier transform infrared (FTIR) spectroscopy, Field emission scanning electron microscopy (FE-SEM), Raman spectroscopy, and atomic force microscopy (AFM) techniques were employed to confirm the structural integrity and specificity of the FPV-MWCNT formulation. The results demonstrated a remarkable entrapment efficiency of 79.57 ± 0.4 %, indicating the successful loading of FPV onto COOH-MWCNTs. FE-SEM and AFM analyses further confirmed the well-dispersed and elongated structure of the FPV-MWCNT formulation, without any signs of fracture, ensuring the stability and integrity of the drug delivery system. Moreover, particle size analysis revealed an average size of 290.1 nm, firmly establishing the nanoscale range of the formulation, with a zeta potential of 0.230 mV, signifying the system's colloidal stability. In vitro drug release studies conducted in methanolic phosphate buffer saline (PBS) at pH 7.4 and methanolic acetate buffer at pH 5 demonstrated sustained drug release from the FPV-MWCNT formulation. Over a period of 96 h, the formulation exhibited a cumulative drug release of 91.43 ± 2.3 %, showcasing the controlled and sustained release profile. Furthermore, hemolysis studies indicated a notable reduction in the toxicity of both FPV and MWCNT upon conjugation, although the percent hemolysis increased with higher concentrations, suggesting the need for careful consideration of dosage levels. In conclusion, the findings from this study underscore the potential of the FPV-MWCNT formulation as an effective and promising drug-conjugated system for delivering antiretroviral drugs. The successful encapsulation, sustained drug release, and reduced toxicity make FPV-MWCNT a compelling candidate for enhancing the therapeutic efficacy of protease inhibitor antiretroviral drugs in the treatment of HIV. The developed delivery system holds great promise for future advancements in HIV treatment and paves the way for further research and development in the field of drug delivery utilizing carbon nanotube-based systems.


Subject(s)
Anti-Infective Agents , HIV Infections , Nanotubes, Carbon , Humans , Nanotubes, Carbon/chemistry , Protease Inhibitors , Hemolysis , Drug Delivery Systems , Enzyme Inhibitors , Antiviral Agents
17.
Biofactors ; 50(2): 232-249, 2024.
Article in English | MEDLINE | ID: mdl-37702264

ABSTRACT

Piceatannol is a naturally occurring hydroxylated resveratrol analogue that can be found in a variety of fruits and vegetables. It has been documented to have a wide range of beneficial effects, including anti-inflammatory, antioxidant, anti-aging, anti-allergic, antidiabetic, neuroprotective, cardioprotective, and chemopreventive properties. Piceatannol has significantly higher antioxidant activity than resveratrol. Piceatannol has been shown in preclinical studies to have the ability to inhibit or reduce the growth of cancers in various organs such as the brain, breast, lung, colon, cervical, liver, prostate, and skin. However, the bioavailability of Piceatannol is comparatively lower than resveratrol and other stilbenes. Several approaches have been reported in recent years to enhance its bioavailability and biological activity, and clinical trials are required to validate these findings. This review focuses on several aspects of natural stilbene Piceatannol, its chemistry, and its mechanism of action, and its promising therapeutic potential for the prevention and treatment of a wide variety of complex human diseases.


Subject(s)
Noncommunicable Diseases , Stilbenes , Humans , Resveratrol/therapeutic use , Antioxidants/pharmacology , Antioxidants/therapeutic use , Stilbenes/pharmacology , Stilbenes/therapeutic use , Stilbenes/chemistry
18.
Autoimmun Rev ; 23(3): 103508, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38160960

ABSTRACT

The complicated relationships between autoimmunity, COVID-19, and COVID-19 vaccinations are described, giving insight into their intricacies. Antinuclear antibodies (ANA), anti-Ro/SSA, rheumatoid factor, lupus anticoagulant, and antibodies against interferon (IFN)-I have all been consistently found in COVID-19 patients, indicating a high prevalence of autoimmune reactions following viral exposure. Furthermore, the discovery of human proteins with structural similarities to SARS-CoV-2 peptides as possible autoantigens highlights the complex interplay between the virus and the immune system in initiating autoimmunity. An updated summary of the current status of COVID-19 vaccines is presented. We present probable pathways underpinning the genesis of COVID-19 autoimmunity, such as bystander activation caused by hyperinflammatory conditions, viral persistence, and the creation of neutrophil extracellular traps. These pathways provide important insights into the development of autoimmune-related symptoms ranging from organ-specific to systemic autoimmune and inflammatory illnesses, demonstrating the wide influence of COVID-19 on the immune system.


Subject(s)
Autoimmunity , COVID-19 Vaccines , COVID-19 , SARS-CoV-2 , Humans , COVID-19/immunology , COVID-19/prevention & control , SARS-CoV-2/immunology , COVID-19 Vaccines/immunology , Autoimmunity/immunology , Autoimmune Diseases/immunology , Autoantigens/immunology
19.
Cell Signal ; 113: 110911, 2024 01.
Article in English | MEDLINE | ID: mdl-37805102

ABSTRACT

The rewiring of cellular metabolism is a defining characteristic of cancer, as tumor cells adapt to acquire essential nutrients from a nutrient-poor environment to sustain their viability and biomass. While hypoxia has been identified as a major factor depriving cancer cells of nutrients, recent studies have revealed that cancer cells distant from supporting blood vessels also face nutrient limitations. To overcome this challenge, hypoxic cancer cells, which heavily rely on glucose as an energy source, employ alternative pathways such as glycogen metabolism and reductive carboxylation of glutamine to meet their energy requirements for survival. Our preliminary studies, alongside others in the field, have shown that under glucose-deficient conditions, hypoxic cells can utilize mannose and maltose as alternative energy sources. This review aims to comprehensively examine the hypoxic cancer microenvironment, its association with drug resistance, and potential therapeutic strategies for targeting this unique niche. Furthermore, we will critically evaluate the current literature on hypoxic cancer microenvironments and explore state-of-the-art techniques used to analyze alternate carbohydrates, specifically mannose and maltose, in complex biological fluids. We will also propose the most effective analytical methods for quantifying mannose and maltose in such biological samples. By gaining a deeper understanding of the hypoxic cancer cell microenvironment and its role in drug resistance, novel therapeutic approaches can be developed to exploit this knowledge.


Subject(s)
Maltose , Neoplasms , Humans , Cell Hypoxia , Maltose/pharmacology , Maltose/therapeutic use , Mannose/pharmacology , Mannose/therapeutic use , Neoplasms/metabolism , Hypoxia , Glucose/pharmacology , Tumor Microenvironment , Drug Resistance
20.
Cell Signal ; 115: 111013, 2024 03.
Article in English | MEDLINE | ID: mdl-38113978

ABSTRACT

The gut microbiota present in the human digestive system is incredibly varied and is home to trillions of microorganisms. The gut microbiome is shaped at birth, while numerous genetic, dietary, and environmental variables primarily influence the microbiome composition. The importance of gut microbiota on host health is becoming more widely acknowledged. Digestion, intestinal permeability, and immunological and metabolism responses can all be affected by changes in the composition and function of the gut microbiota. There is mounting evidence that the microbial population's complex traits are important biomarkers and indicators of patient outcomes in cancer and its therapies. Numerous studies have demonstrated that changed commensal gut microorganisms contribute to the development and spread of cancer through various routes. Despite the ongoing controversy surrounding the gut microbiome and gastrointestinal cancer, accumulating evidence points to a potentially far more intricate connection than a simple cause-and-effect relationship. SIMPLE SUMMARY: Due to their high frequency and fatality rate, gastrointestinal cancers are regarded as a severe public health issue with complex medical and economic burdens. The gut microbiota may directly or indirectly interact with existing therapies like immunotherapy and chemotherapy, affecting how well a treatment works. The gut microbiome influences the immune response's activity, function, and development. Generally, certain gut bacteria impact the antitumor actions during cancer by creating particular metabolites or triggering T-cell responses. Yet, certain bacterial species have been found to promote cellular proliferation and metastasis in cancer, and comprehending these interactions in the context of cancer may help identify possible treatment targets. Notwithstanding the improvements in the field, additional research is still required to comprehend the underlying processes, examine the effects on existing therapies, and pinpoint certain bacteria and immune cells that can cause this interaction.


Subject(s)
Gastrointestinal Microbiome , Gastrointestinal Neoplasms , Microbiota , Infant, Newborn , Humans , Bacteria/genetics
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