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OBJECTIVE: Isorhamnetin, a naturally occurring flavonoid compound, holds paramount importance as a primary constituent within several medicinal plants, exhibiting profound pharmacological significance. The aim of this study is to investigate the pain-relieving attributes of isorhamnetin in murine models through both formalin-induced pain and diabetic neuropathy scenarios. MATERIALS AND METHODS: To achieve our objective, isorhamnetin was orally administered to mice at varying dosage levels (10 to 100 mg/ kg). Pain-related behaviors were assessed using the formalin test during its secondary phase. Additionally, the potential pain-alleviating effect of isorhamnetin was evaluated in a diabetic neuropathy model induced by streptozotocin. Additionally, we carried out advanced interventions using naloxone, which is a well-known antagonist of opioid receptors, yohimbine, which blocks a2-adrenergic receptors, and methy-sergide, which inhibits serotonergic receptors, during the formalin test. RESULTS: The oral intake of isorhamne-tin showed a decrease in behaviors associated with pain that was proportional to the dose observed during the second phase of the formalin test when induced by formalin. In the diabetic neuropathy model, isorhamnetin administration effectively reversed the reduced pain threshold observed. Notably, naloxone, the opioid receptor antagonist, effectively counteracted the pain-relieving effect produced by isorhamne-tin in the formalin test, whereas yohimbine and methysergide did not yield similar outcomes. Isorhamnetin also led to a reduction in elevated spinal cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) levels triggered by formalin, with this effect reversed by pre-treatment with naloxone. The compound also suppressed heightened spinal phosphory-lated CREB (p-CREB) levels caused by diabetic neuropathy. CONCLUSIONS: This research determined that isorhamnetin has notable abilities to relieve pain in models of formalin-induced pain and diabetic neuropathy. The pain-relieving mechanism of isorhamnetin in the formalin-induced pain model seems to be connected to the activation of spinal opioid receptors and the adjustment of CrEb protein amounts. This insight improves our knowledge of how isorhamnetin could be used therapeutically to treat pain conditions stemming from formalin-induced pain and diabetic neuropathy. [ABSTRACT FROM AUTHOR]

Farah M Abdulkhaleq,1 Tawfiq M Alhussainy,1 Mujtaba M Badr,2 Asad A Abu Khalil,2 Omar Gammoh,3 Bayan Y Ghanim,2 Nidal A Qinna1,2 1Department of Pharmacology and Biomedical Sciences, Faculty of Pharmacy and Medical Sciences, University of Petra, Amman, Jordan; 2University of Petra Pharmaceutical Center (UPPC), University of Petra, Amman, Jordan; 3Department of Pharmacy, Faculty of Health Sciences, American University of Madaba, Madaba, Jordan Background: Several vitamins, including C, E, and B12, have been recognized as antioxidants and have shown hepatoprotective effects against the hepatotoxicity caused by acetaminophen (APAP) overdose. The current investigation aims to study the effect of these vitamins and their combination in protecting the liver from APAP hepatotoxicity in rats. Materials and methods: An in vitro model of freshly isolated rat hepatocytes was utilized for assessing hepatocyte mitochondrial activity conducted by cell proliferation assay (MTT). The isolated hepatocytes were treated with vitamin C, vitamin E, vitamin B12 and their combination, with and without further addition of toxic concentrations of APAP. In addition, an in vivo experiment was carried out on Sprague Dawley rats treated intraperitoneally for 8 days with emulsions of the vitamins or their combination prior to injecting them with APAP. Results: In vitro results showed that vitamins C and B and the combination preparation significantly increased the percentage of hepatocyte mitochondrial activity, both with and without the addition of APAP (P

OBJECTIVE: This study aimed to assess the antinociceptive activity of herbacetin using chemically and thermally induced nociception in a mouse model. MATERIALS AND METHODS: The antinociceptive effects of various herbacetin doses (50, 100, 150, and 200 μg/kg) were assessed in mice using the acetic acid-induced writhing test, hot plate test, and formalin-induced paw-licking assay. The effects were compared to those of mice treated with acetylsalicylic acid or morphine in the presence or absence of naloxone (an opioid receptor antagonist). Capsaicin-and glutamate-induced paw-licking tests were also used to evaluate the involvement of the vanilloid and glutamatergic systems, respectively. Pro-inflammatory mediators: Interleukin-1-beta (IL-1β), Tumour Necrosis Factor alpha (TNF-α), Interferon- gamma (IFN-γ), and Nitric Oxide (NO) were also assessed. RESULTS: Herbacetin produced significant dose-dependent inhibition of nociceptive behavior in the acetic acid-induced writhing test, showing 65% inhibition at a dose of 200 μg/kg. Herbacetin also caused a significant increase in the latency period in response to the hot plate test (70% at 200 μg/kg), and significantly inhibited both the neurogenic and inflammatory phases in the formalin-induced paw-licking test. Naloxone significantly reverses the effect of herbacetin in both the hot plate and formalin-induced paw-licking test. Moreover, herbacetin significantly inhibited the neurogenic nociception induced by intraplantar injections of capsaicin and glutamate (75% and 48%, respectively, at a dose of 200 μg/kg). Pro-inflammatory cytokines IL-1β, TNF-α, IFN-γ, and NO in the serum of mice were assessed. These cytokines were significantly inhibited by herbacetin (100 and 200 μg/kg). Thus, herbacetin exhibited peripheral and central antinociception through the modulation of vanilloid receptors, opioid receptors, and the glutamatergic system. CONCLUSIONS: Herbacetin possesses antinociceptive activity in adult mice that is mediated through both central and peripheral pathways. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The aim of this study was to evaluate the effects of orally administering Thymus vulgaris leaves on memory performance, anxiety, depression, and sleep quality in a sample of university students. PATIENTS AND METHODS: This randomized controlled trial included 106 students who were randomly assigned to one of two groups. The first group received 500 mg of Thymus vulgaris leaves twice daily, while the second group received a placebo. The intervention period lasted for one month. The participants' memory performance (both prospective and retrospective), levels of anxiety and depression, and sleep quality were assessed using the Prospective and Retrospective Memory Questionnaire (PRMQ), Hospital Anxiety and Depression Scale (HADS), and Pittsburgh Sleep Quality Inventory (PSQI) at the beginning of the study and after one month. RESULTS: The findings revealed significant reductions in the scores of all scales and subscales, with the exception of the sleep latency and sleep duration components of the Pittsburgh Sleep Quality Inventory, among the group that received Thymus vulgaris leaves in comparison to the control group. CONCLUSIONS: Thymus vulgaris leaves, a traditional food source, demonstrate potential for enhancing both prospective and retrospective memory, alleviating anxiety and depression, and improving sleep quality in university students. [ABSTRACT FROM AUTHOR]

OBJECTIVE: This study's primary objective was to explore and validate the pain-relieving and inflammation-reducing properties of fisetin, a flavonoid known for its antioxidant benefits, using different mouse models. MATERIALS AND METHODS: We assessed fisetin's pain-relieving effects using mouse models exposed to both heat-induced and chemical-induced pain. The inflammation-reducing capacity of fisetin was evaluated using the carrageenan-triggered paw swelling test, focusing on the influx of leukocytes in the peritoneal space. The air pouch test was utilized to determine fisetin's ability to counteract proinflammatory cytokines. The performance of fisetin, when paired with opioid blockers, was analyzed, and juxtaposed with results from conventional medicines. The muscle-relaxing potential of fisetin was assessed through the open field assessment. RESULTS: Fisetin consistently demonstrated marked anti-inflammatory actions across various models. It also proved to be effective in reducing pain in the pain-induced models. When combined with opioid blockers, fisetin's effects were on par with those of traditional medications. Noteworthily, fisetin displayed muscle-relaxing properties in the open-field assessment. CONCLUSIONS: The compiled data showcases fisetin as a powerful anti-inflammatory agent with significant pain-relieving capacities, positioning it as a promising contender for pain treatment modalities. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The primary objective was to study the association between fingolimod and the frequency of depression, anxiety, and insomnia symptoms among a cohort of Multiple Sclerosis (MS) patients with stress. The secondary objective was to examine the association between patient characteristics and these psychiatric symptoms. PATIENTS AND METHODS: Patients with MS and stress were recruited according to the Arabic version of the Perceived Stress Scale (PSS). Psychiatric outcomes were measured by validated scales. Logistic regression was used to estimate adjusted odds ratios (aORs) with 95% confidence intervals (CIs). Data from 324 participants were analyzed. RESULTS: Fingolimod was associated with a significantly lower adjusted odds ratio for depression (aOR 0.58, 95% CI 0.35-0.97, p<0.05) but less associated with anxiety (aOR 0.63, 95% CI 0.35-1.01, p=0.05) and insomnia (aOR 0.88, 95% CI 0.52-1.51, p=0.64). CONCLUSIONS: Close monitoring of mental health is required for patients with MS using disease-modifying therapies. [ABSTRACT FROM AUTHOR]

Rationale: Early-life maternal separation can lead to anxiety-like and depression-like behaviors in mice reared under maternal separation conditions. Scopoletin, a compound with anti-inflammatory and antidepressant properties, may offer therapeutic benefits, but its effectiveness against behaviors induced by maternal separation during adulthood remains unexplored., Objectives: This study investigates scopoletin's efficacy in alleviating anxiety-like and depression-like phenotypes in male mice subjected to early-life maternal separation., Methods: Male C57BL/6J mice experienced daily maternal separation for 4 h from postnatal day (PND) 2 to 21. From postnatal day 61(PND 61), scopoletin was administered intraperitoneally at 20 mg/kg/day for four weeks. Behavioral and biochemical assessments were conducted at postnatal day 95 (PND 95)., Results: Maternally separated mice displayed marked anxiety-like and depression-like behaviors, evident in behavioral tests like the open field and elevated plus maze. These mice also showed increased immobility in the forced swimming and tail suspension tests. Biochemically, there were elevated levels of IL-1β, IL-6, and TNF-α in the hippocampus, with a decrease in Sirt1 and upregulation in NF-κB p65 expression. Scopoletin treatment significantly mitigated these behavioral abnormalities, normalizing both anxiety-like and depression-like behaviors. Correspondingly, it reduced the levels of pro-inflammatory cytokines and reinstated the expression of Sirt1 and NF-κB p65., Conclusions: Scopoletin effectively reverses the adverse behavioral and biochemical effects induced by early-life maternal separation in male mice, suggesting its potential as a therapeutic agent for treating anxiety-like and depression-like behaviors. Modulation of neuroinflammatory pathways and the Sirt1/NF-κB signaling axis is one possible mechanism., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The escalating global burden of cardiovascular diseases is a growing concern. Numerous research studies have established that plant-derived polyphenols, including α-pinene-a monocyclic monoterpene found in various plant essential oils-have significant effects on key cardiovascular mechanisms. These effects are mediated through their influence on antioxidant systems, cellular signaling pathways, and gene transcription processes. This study investigated the protective effects of α-pinene against cardiac damage caused by carbon tetrachloride (CCl 4 ) in Wistar rats. Rats were divided into four groups: a control group receiving saline, a disease control group-administered CCl 4 (1 mL/kg body weight, intraperitoneally), and two treatment groups receiving α-pinene orally at doses of 50 mg/kg and 100 mg/kg body weight alongside CCl 4 , to assess its dose-dependent effects. We conducted comprehensive evaluations, including assessments of serum and cardiac toxicity biomarkers, inflammatory mediators, antioxidant defense mechanisms, lipid peroxidation levels, lipid profiles, and histopathological analyses. CCl 4 exposure resulted in notable increases in free fatty acids (FFA), total cholesterol (TC), triglycerides (TG), phospholipids (PL), low-density lipoprotein (LDL), and very low-density lipoprotein (VLDL) levels, and a decrease in high-density lipoprotein (HDL) levels. Treatment with α-pinene at 100 mg/kg effectively counteracted these lipid profile changes. CCl 4 also caused lipid oxidation and a reduction in antioxidant activities, which were restored to normal levels with α-pinene treatment at 100 mg/kg body weight. Moreover, an upsurge in inflammatory markers (interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and high-sensitivity C-reactive protein (Hs-CRP)) and cardiac toxicity biomarkers (creatine kinase (CK), and creatine kinase-myocardial band (CK-MB) and troponin) induced by CCl 4 intoxication was reversed by α-pinene. Histopathological studies further validated these findings. The study concludes that α-pinene, administered at a dosage of 100 mg/kg body weight, effectively alleviates cardiac injury induced by CCl 4 . The data suggest that α-pinene exerts its protective effects through modulation of various signaling pathways involved in CCl 4 -induced cardiac toxicity., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Clinicians have noted that the ongoing war on Gaza has had a psychological impact on people with multiple sclerosis (PwMS) whose mental health is particularly vulnerable during stressful times such as these. The present study sought to examine the prevalence and correlates of posttraumatic stress disorder (PTSD) symptoms among PwMS in Jordan during the Gaza war outbreak., Methods: This was a cross-sectional study involving 171 patients (PwMS) out of 372 patients approached (46% response rate) who were being seen in the MS unit at Al Bashir Hospital, Ammann, Jordan. Inclusion criteria required that participants had been following daily news updates of the October 7 war in Gaza during a period of 4 months., Results: Of participants, 125 (73.1%) were female, 98 (57.3%) were on therapy for less than five years, and 30 (17.5%) reported having a relapse during the past 6 months. Significant PTSD symptoms were identified in 58.5% (100 of 171 participants). Those at higher risk were the unemployed (OR = 2.14, 95% CI = 1.13-4.07, P = 0.02), whereas patients receiving dimethyl fumarate (19.9%) were at lower risk (OR = 0.43, 95% CI = 0.19-0.94, P = 0.02)., Conclusion: The high rate of significant PTSD symptoms among people with MS in this study underscores the need for attention by primary care providers and the implementation of a comprehensive multidisciplinary approach to optimize the mental well-being of this fragile population., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The circulating violent news about the war on Gaza is believed to impact the mental health status of people globally especially in Jordan, the closest country to Palestine. Also, women are more vulnerable to mental distress., Aims: This study investigates the prevalence and correlates of post-traumatic stress disorder (PTSD), depression, insomnia, and fibromyalgia among Jordanian females exposed to the Gaza war news., Method: In a comprehensive cross-sectional inquiry, we applied validated scales to assess the severity of PTSD, depression, insomnia, and fibromyalgia symptoms in a dataset comprising 1,044 females., Results: The findings revealed that 32.3% exhibited severe PTSD symptoms, 53.4% had severe depressive symptoms, 48.2% reported severe insomnia, and 17.2% were diagnosed with fibromyalgia. Exploring demographic factors, the study established statistically significant correlations ( p  < .05) between the evaluated symptoms and various variables. Notably, individuals of Palestinian nationality, employed as teachers or housewives, those using over-the-counter analgesics for fibromyalgia, and those with chronic diseases exhibited elevated prevalence rates of the investigated conditions., Conclusions: This pioneering study, the first of its kind, delves into the acute psychiatric repercussions of the October 7th conflict on Jordanian females. The alarming prevalence of severe symptoms underscores the urgent need for timely psychiatric intervention.

Background: Migraine is characterized by sudden acute episodes of pain, with a global prevalence of 18% among all age groups. It is the second leading cause of years lived with disability worldwide. Prophylactic treatment is important in managing migraine; however, its efficacy and safety are debated. This study aimed to evaluate the efficacy of desvenlafaxine in female patients with migraine. Methods: We conducted a retrospective observational case study involving 10 women diagnosed with migraine who were treated with desvenlafaxine. We measured the number of migraine days per month, average headache duration in minutes, headache severity using a visual analog scale, use of acute medications, and frequency of acute medication use per week. Results: Desvenlafaxine significantly reduced the number of migraine days from 14.70 ± 3.68 at baseline to 2.50 ± 2.50 at follow-up ( p < 0.05). The average headache duration dropped from 131.25 ± 32.81 min to 52.50 ± 44.64 min. Headache severity scores improved from 6.80 ± 1.49 at baseline to 0.80 ± 0.92 at follow up, the frequency of acute medication use per week reduced from 3.30 ± 1.49 at baseline to 0.80 ± 0.92, and the frequency of acute medication use decreased from 3.30 ± 1.49 times per week to 0.80 ± 0.92. Conclusions: Desvenlafaxine shows potential as an effective prophylactic therapy for migraine. Larger-scale studies are necessary to further explore its benefits.

Depression, a significant mental health disorder, is under intense research scrutiny to uncover its molecular foundations. Epigenetics, which focuses on controlling gene expression without altering DNA sequences, offers promising avenues for innovative treatment. This review explores the pivotal role of epigenetics in depression, emphasizing two key aspects: (I) identifying epigenetic targets for new antidepressants and (II) using personalized medicine based on distinct epigenetic profiles, highlighting potential epigenetic focal points such as DNA methylation, histone structure alterations, and non-coding RNA molecules such as miRNAs. Variations in DNA methylation in individuals with depression provide opportunities to target genes that are associated with neuroplasticity and synaptic activity. Aberrant histone acetylation may indicate that antidepressant strategies involve enzyme modifications. Modulating miRNA levels can reshape depression-linked gene expression. The second section discusses personalized medicine based on epigenetic profiles. Analyzing these patterns could identify biomarkers associated with treatment response and susceptibility to depression, facilitating tailored treatments and proactive mental health care. Addressing ethical concerns regarding epigenetic information, such as privacy and stigmatization, is crucial in understanding the biological basis of depression. Therefore, researchers must consider these issues when examining the role of epigenetics in mental health disorders. The importance of epigenetics in depression is a critical aspect of modern medical research. These findings hold great potential for novel antidepressant medications and personalized treatments, which would significantly improve patient outcomes, and transform psychiatry. As research progresses, it is expected to uncover more complex aspects of epigenetic processes associated with depression, enhance our comprehension, and increase the effectiveness of therapies.

Background and Objectives : Although physical health is always studied for women with diabetes, the mental health aspect is generally overlooked for this chronic disease. The present study aimed to examine the prevalence of psychosomatic symptoms, namely, fibromyalgia syndrome, depression, anxiety, and insomnia, and how these symptoms related to the medications used in a cohort of women diagnosed with type 2 diabetes (DM) in Jordan. Materials and Methods : This cross-sectional study recruited women diagnosed with type 2 diabetes, and validated scales (PSRS, PHQ-9, GAD-7, and ISI-A) for fibromyalgia syndrome, depression, anxiety, and insomnia were used. The associations between the different medications used and the dependent variables were examined using four separate multivariate logistic regression models. Results : Data were analyzed from 213 participants. Of them, 27.2% met the threshold for fibromyalgia syndrome diagnosis, 38% met the threshold for severe depression, 36.2% met the threshold for severe anxiety, and 39.9% met the threshold for severe insomnia. Fibromyalgia syndrome symptoms were significantly associated with glimepiride (OR = 1.92, CI = 1.00-3.68), β-blockers (OR = 2.21, CI = 1.03-4.70), diuretics (OR = 3.13, CI = 1.26-7.78), herbal remedies (OR = 2.12, CI = 0.98-4.55), and prescriptions for centrally acting medication (OR = 2.78, CI = 1.24-6.29). Significant associations were found between depression and diuretics (OR = 2.62, CI = 1.05-6.67), over-the-counter nonsteroidal anti-inflammatory drugs (NSAIDs) (OR = 3.49, CI = 1.69-7.23), and herbal remedies (OR = 5.07, CI = 2.40-10.69). In addition, anxiety was significantly related to diuretics (OR = 2.48, CI = 1.02-6.02), and OTC NSAIDs (OR = 2.60, CI = 1.29-5.21). Significant associations were evident between insomnia and β-blockers (OR = 3.23, CI = 1.51-6.95), acetaminophen (OR = 2.09, CI = 1.06-4.08), NSAIDs (OR = 4.61, CI = 2.18-9.76), and herbal remedies (OR = 5.95, CI = 2.71-13.07). Conclusions : Medications are associated with high burden of fibromyalgia syndrome, depression, anxiety, and insomnia. These findings underscore the importance of revising and optimizing the pharmacotherapy of these vulnerable patients, performing close mental health monitoring and the implementation of non-pharmacological interventions by integrating mental health services for women with chronic diseases such as diabetes.

Background and Objectives : The current war on the Gaza strip and the circulating violent content is believed to negatively impact the mental health of the Palestinians living in refugee camps outside their homeland. This study explores the prevalence and correlates of depression, anxiety, and insomnia in a cohort of female Palestinian refugees in Jordan who have family members entangled in the persistent conflict in the Gaza strip. Materials and Methods : This cross-sectional study employed validated tools to assess depression, anxiety, and insomnia in women residing in a Gaza camp located in Jerash, Jordan. The correlates were determined by regression analysis. Results : The study unearths disconcerting statistics from 177 recruited women, revealing alarmingly high rates of severe depression (73%), anxiety (60%), and insomnia (65%). Multivariable analysis revealed that severe depression was significantly associated with prior diagnosis with chronic diseases (OR = 3.0, CI = 1.36-6.58), and having a first-degree relative in Gaza (OR = 0.42, CI = 0.20-0.85). Additionally, severe insomnia was associated with "losing relatives or friends in the war" (OR = 3.01, CI = 1.41-6.44), and "losing connection with families and friends" (OR = 3.89, CI = 1.58-9.53). Conclusions : The implications of these results are profound, underscoring the immediate and imperative need for both medical and psychiatric interventions aimed at addressing the substantial psychological burden borne by this population because of the ongoing conflict.

Objective: The present study examined the prevalence and correlates of insomnia and fatigue in patients with type-2 diabetes in Jordan. Methods: This was a cross-sectional online study involving a convenience sample of 390 patients with type-2 diabetes. Insomnia was assessed by the Insomnia-Severity Index (ISI-A) and fatigue by the Brief Fatigue Inventory (BFI-A). Results: Severe insomnia was present in 132 patients (33.8%), and was correlated with length of diabetes (diagnosis >5 years) (OR = 2.13, 95% CI = 1.19-3.81, P = 0.01), presence of uncontrolled diabetes (OR = 1.97, 95% CI = 1.45-2.69, P < 0.001), taking gabapentin (OR = 2.07, 95% CI = 1.07-4.01, P = 0.003), and age (<40 years) (OR = 0.30, 95% CI = 0.13-0.69, P = 0.005). Significant fatigue was also prevalent and correlated with gender (female) (B = 9.25, t = 4.48, P < 0.001), age (<40 years) (B = 7.56, t = 2.56, P = 0.01), a diagnosis of hypertension (B = 4.74, t = 2.03, P = 0.04), uncontrolled diabetes (B = 7.21, t = 4.82, P < 0.001), and taking a sulfonylurea (B = 8.03, t = 3.37, P < 0.001), carbamazepine (B = 10.93, t = 2.65, P = 0.008), or gabapentin (B = 12.60, t = 3.83, P < 0.001). Conclusion: Given the high prevalence of insomnia and fatigue in this population, increased attention by primary healthcare providers to these symptoms in diabetic patients is required, particularly in developing countries such as Jordan., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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., Competing Interests: The Authors declared no conflict of interest, (African Journal of Reproductive Health © 2024)

Background : The relationship between adult ADHD symptoms in People with Multiple Sclerosis (PwMS) is understudied. This study aimed to answer two questions: are PwMS more likely to experience higher ADHD symptoms versus healthy subjects? And what are the correlates of severe ADHD symptoms in PwMS? Methods : This study followed a cross-sectional design with predefined inclusion criteria. The Adult ADHD Self-Report Scale-V1.1 (ASRS) was used to assess the ADHD symptoms severity. Results : Data were analyzed from 171 PwMS and 200 controls. Regression analysis revealed that PwMS were at a significantly (B = 3.05, t = 2.24, 95% CI = 0.37-5.73, p = 0.02) higher risk to report higher ADHD scores versus controls. In addition, PwMS with relapses in the last 6 months and PwMS reporting smartphone addiction were at a significantly higher risk for severe ADHD (B = 7.19, t = 269, 95% CI = 1.91-12.48, p = 0.008) and (B = 9.18, t = 3.47, 95% CI = 3.97-14.41, p = 0.001), respectively. In conclusion, diagnosis with MS in our study was identified as a risk for higher ADHD symptoms. Conclusions : Further research is required to establish this relationship, and holistic medical and psychological interventions are required to improve the cognitive status of PwMS.

Background and Objectives: The investigation of the psychosomatic symptoms in women residing in developing countries is still emerging. To be precise, the prevalence and correlates of severe fibromyalgia, depression, anxiety, and insomnia are understudied in Arab women, as these symptoms could relate to improper self-medication. This study mainly investigated the association between self-medication with analgesics and fibromyalgia, depression, anxiety, and insomnia symptoms among a community-based cohort of females in Jordan. Materials and Methods: We used a web-based cross-sectional study design. Fibromyalgia, depression, anxiety, and insomnia were assessed using validated scales. The used over-the-counter (OTC) painkillers were recorded. Results: Data were analyzed from 741 women, and fibromyalgia was screened in 16.4%, depression in 37.4%, anxiety in 27.8%, and insomnia in 38.3%. Fibromyalgia was associated with "married" (OR = 1.5, 95% CI = 1.017-2.305), "using OTC acetaminophen" (OR = 1.75, 95% CI = 1.15-2.69), "using herbal remedies" (OR = 2.02, 95% CI = 1.33-3.07), and "using antiseizure medications" (OR = 2.43, 95% CI = 1.38-4.28). Severe depression was significantly associated with "age" (OR = 0.97, 95% CI = 0.96-0.99), "high school education" (OR = 1.90, 95% CI = 1.21-2.98), "smoking" (OR = 1.72, 95% CI = 1.15-2.56), "OTC acetaminophen" (OR = 1.40, 95% CI = 1.02-1.92), "OTC non-steroidal anti-inflammatory drugs" (OR = 1.75, 95% CI = 1.15-2.65), and "antiseizures" (OR = 2.19, 95% CI = 1.30-3.70). Severe anxiety was significantly associated with "smoking" (OR = 2.08, 95% CI = 1.40-3.12), "OTC acetaminophen" (OR = 1.48, 95% CI = 1.06-2.06), and "antiseizure medications" (OR = 2.04, 95% CI = 1.22-3.41). Severe insomnia was significantly associated with "age" (OR = 0.98, 95% CI = 0.96-0.99), "high school education" (OR = 1.58, 95% CI = 1.01-2.47), "smoking" (OR = 1.51, 95% CI = 1.01-2.25), "OTC non-steroidal anti-inflammatory drugs" (OR = 1.74, 95% CI = 1.13-2.64), "antiseizure medications" (OR = 1.84, 95% CI = 1.09-3.11), and "No analgesics" (OR = 0.48, 95% CI = 0.32-0.71). Conclusions: Self-medication with analgesics is associated with a high burden of psychosomatic symptoms in Arab women, and awareness campaigns are required to guide self-medication behavior.

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-1β, 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., (© 2024. The Author(s).)

The aim of this investigation was to explore the protective impacts and mechanisms of Anastatica hierochuntica essential oil (EOAH) against dextran sulfate sodium (DSS)-induced experimental colitis in mice. EOAH demonstrated a reduction in DSS-induced body weight decline, disease activity index (DAI), colon length reduction, colonic tissue damage, and myeloperoxidase (MPO) activity. The essential oil significantly mitigated the production of pro-inflammatory agents including TNF-α, IL-1β, and IL-12. Further analysis revealed that EOAH's anti-inflammatory effects involved the regulation of NF-κB and PPARγ pathways, as well as the inhibition of NLRP3 activation in colitis mice. Notably, EOAH treatment elevated the levels of beneficial commensal bacteria such as Lactobacillus and Bifidobacteria, while reducing Escherichia coli levels in the mice's feces. In addition, EOAH restored the expression of occludin and ZO-1 proteins in colonic tissues affected by ulcerative colitis (UC). These findings indicate that supplementing with EOAH might offer a novel therapeutic approach for UC prevention., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Jordan and Palestine are tightly related countries as the same families live in the two adjacent countries. The present study sought to examine the prevalence and determinants of Post-Traumatic Stress Disorder (PTSD)symptoms, insomnia, and fatigue among a cohort of People with Epilepsy (PWE) in Jordan. This is a cross-sectional study with inclusion criteria. PTSD, insomnia, and fatigue were assessed using validated scales. Data were analyzed from 109 PWE, PTSD symptoms were screened in (35.5 %), and Insomnia was screened in 51.8 %, moreover, fatigue mean score ± SD was 44.64 ± 26.96. PTSD symptoms were significantly associated with "females" and "age above 30 years" Insomnia severity was associated with "females". Also, the regression results demonstrated that "abstinence from social media" was significantly related to lower insomnia severity. Higher fatigue severity was associated with "married" and "Generalized Tonic-Clonic Seizures", whereas, lower fatigue severity was associated with "males", and with "levetiracetam". Our findings indicate the need for actions to alleviate mental health deterioration in PWE., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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.

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., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The flavonoid compound Isorhamnetin (IRMN) is known for its considerable pharmacological properties, which include antioxidant and anti-inflammatory effects, as well as significant protective actions on heart health. However, the potential of IRMN to guard against heart damage caused by cisplatin (CP), a common chemotherapeutic agent, and the specific mechanisms involved, remain unexplored areas. This research was designed to investigate how IRMN counters CP-induced heart toxicity. In our study, mice were orally given IRMN at 50 or 150 mg/kg/day for a week, followed by CP injections (5 mg/kg/day) on the third and sixth days. The animals were euthanized under sodium pentobarbital anesthesia (50 mg/kg, intraperitoneally) on the eighth day to collect blood and heart tissues for further examination. Our findings reveal that IRMN administration significantly reduced the heart damage and the elevation of heart injury markers such as cardiac troponin I, creatine kinase, and lactate dehydrogenase induced by CP. IRMN also effectively lowered oxidative stress markers, including reactive oxygen species and malondialdehyde, while boosting ATP production and antioxidants like superoxide dismutase, catalase, and glutathione. The compound's capability to diminish the levels of pro-inflammatory cytokines like tumor necrosis factor-alpha and interleukin-6, alongside modulating apoptosis-regulating proteins (enhancing Bcl-2 while suppressing Bax and Caspase-3 expression), further underscores its cardioprotective effect. Notably, IRMN modulated the p62-Keap1-Nrf2 signaling pathway, suggesting a mechanism through which it exerts its protective effects against CP-induced cardiac injury. These insights underscore the potential of IRMN as an effective adjunct in cancer therapy, offering a strategy to mitigate the cardiotoxic side effects of cisplatin., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: Mental health in people with epilepsy (PWE) is often overlooked, especially in developing countries. Purpose: Consequently, the current work had two objectives: (1) to estimate the burden of depression, anxiety, insomnia, and stress, and (2) to examine the association of these psychiatric/psychological symptoms with levetiracetam and other relevant clinical factors in a cohort of Jordanian PWE. Research Design: This is a cross-sectional study. The demographic and clinical data were recorded. Depression was measured by the Patient Health Questionnaire-9 (PHQ-9, Arabic-validated version) and anxiety by the General Anxiety Disorder-7 (GAD-7, Arabic-validated version). The insomnia severity index (ISI-A, Arabic version) was used to assess sleep quality, and the Perceived Stress Scale (PSS-A, Arabic version) was used to measure perceived stress. Study Sample: Data were analyzed from 280 patients, of which 178 (63.6%) received levetiracetam as monotherapy or as adjuvant. Results: Depression was reported in 150 (53.6%), anxiety in 110 (39.3%), insomnia in 131 (46.8%), and clinically significant stress in 211 (75.4%). At univariate analysis, levetiracetam was not associated with psychiatric symptoms. Multivariate logistic regression revealed that severe depressive symptoms were associated with family history (OR = 2.47, 95% CI = 1.42-4.33, P = .001) and seizure type (OR = 1.69, 95% CI = 1.01-2.80, P = .04), severe anxiety symptoms were associated with family history (OR = 1.90, 95% CI = 1.12-3.23, P = .01), severe insomnia was associated with seizure type (OR = 2.16, 95% CI = 1.33-3.5, P = .002) and severe stress was associated with marital status (OR = 2.37, 95% CI = 1.31-4.29, P = .004). Conclusions: The high psychological burden of PWE is a challenging issue that requires attention and prompt action to control its risk factors. Levetiracetam was not associated with psychiatric symptoms in this study., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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 NO x , 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 NO x , 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., (© 2024. The Author(s).)

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 (β = 8.99, p = 0.001) and NSAIDs (β = 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., (© 2024. The Author(s).)

Inflammatory bowel disease (IBD) is a chronic disease that affects the entire digestive tract. IBD can be classified as ulcerative colitis or Crohn's disease. The key symptoms of IBD include the emergence of abscesses or pustules, pronounced abdominal discomfort, diarrhea, fistulas, and intestinal narrowing, all of which can greatly affect a patient's daily well-being. Several factors, including bacterial infections, immune response irregularities, and changes in the intestinal milieu, can contribute to the onset of IBD. The aim of this study was investigating the role of cirsimaritin in reducing the severity of colitis in animal model. To induce colitis in laboratory Swiss albino mice, a 4% dextran sulfate sodium (DSS) concoction was provided in their hydration source for a duration of six days. Before the onset of colitis, mice were treated with cirsimaritin (10 mg/kg) once daily to evaluate its potential treatment effects against DSS-induced inflammation. The results showed that 10 mg/kg of cirsimaritin decreased colitis severity ( P <0.05). Moreover, cirsimaritin successfully reversed the detrimental effects induced by DSS, including weight reduction, colon truncation, tissue-related damage, increased levels of inflammatory cells in the affected region, and secretion of proinflammatory cytokines. Our findings suggest that cirsimaritin can effectively alleviate acute colitis triggered by DSS., Competing Interests: AUTHOR DISCLOSURE STATEMENT The authors declare no conflict of interest., (© 2024 The Korean Society of Food Science and Nutrition.)

Objective: The Jordanian and the Palestinian communities are tightly related, hence, the current war on Gaza also has social and psychological impacts on Jordanians. Therefore, this study aims to identify the factors associated with severe insomnia and fatigue symptoms in a cohort of Jordanians during the Gaza War outbreak., Methods: This is a cross-sectional web-based questionnaire study. The Insomnia Severity Index-Arabic version (ISI-A), and the Brief Fatigue Inventory-Arabic (BFI-A) were employed, binary logistic and linear regression analyses was performed to identify predictors to severe insomnia and fatigue respectively. Data were collected between December 2023 and January 2024., Results: Data were analyzed from 477 participants, of which 315 (66 %) were females, 107 (22.4 %) reported having a family relative or a friend residing in Gaza, 365 (76.5 %) reported not using any sleep aid, 78 (16.4 %) reported using homeopathy herbal remedies for sleep, and only 52 (10.9 %) reported using over-the-counter sedating antihistamines. Severe insomnia was significantly associated with participants "younger than 30 years old" (OR = 1.81, 95 %CI = 1.22-2.66, p = 0.003), participants "using over-the-counter sedating antihistamines" (OR = 2.78, 95 % CI = 1.27-6.06, p = 0.01). Severe fatigue was significantly associated with "females" (B = 5.87, t = 2.78, p = 0.006), and "smokers" (B = 5.09, t = 2.52, p = 0.01). On the other hand, "not using sleep aids" demonstrated significantly lower odds for severe insomnia (OR = 0.41, 95 % CI = 0.24-0.68, p = 0.001), and fatigue (B = -10.84, t = -4.81, p < 0.001)., Conclusions: Addressing modifiable risk factors such as smoking and sleep self-medications is essential to improve insomnia and fatigue symptoms., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

(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., Competing Interests: The authors declare no conflicts of interest.

Context: Type 2 Diabetes Mellitus (T2D) is a significant health concern worldwide, necessitating novel therapeutic approaches beyond conventional treatments., Objective: To assess isorhamnetin's potential in improving insulin sensitivity and mitigating T2D characteristics through oxidative and glycative stress modulation., Materials and Methods: T2D was induced in mice with a high-fat diet and streptozotocin injections. Isorhamnetin was administered at 10 mg/kg for 12 weeks. HepG2 cells were used to examine in vitro effects on stress markers and insulin sensitivity. Molecular effects on the PGK1 and AKT signalling pathway were also analyzed., Results: The administration of isorhamnetin significantly impacted both in vivo and in vitro models. In HepG2 cells, oxidative and glycative stresses were markedly reduced, indicating a direct effect of isorhamnetin on cellular stress pathways, which are implicated in the deterioration of insulin sensitivity. Specifically, treated cells showed a notable decrease in markers of oxidative stress, such as malondialdehyde, and advanced glycation end products, highlighting isorhamnetin's antioxidant and antiglycative properties. In vivo, isorhamnetin-treated mice exhibited substantially lower fasting glucose levels compared to untreated T2D mice, suggesting a strong hypoglycemic effect. Moreover, these mice showed improved insulin responsiveness, evidenced by enhanced glucose tolerance and insulin tolerance tests. The molecular investigation revealed that isorhamnetin activated PGK1, leading to the activation of the AKT signalling pathway, crucial for promoting glucose uptake and reducing insulin resistance. This molecular action underscores the potential mechanism through which isorhamnetin exerts its beneficial effects in T2D management., Discussion: The study underscores isorhamnetin's multifaceted role in T2D management, emphasizing its impact on oxidative and glycative stress reduction and molecular pathways critical for insulin sensitivity., Conclusion: Isorhamnetin presents a promising avenue for T2D treatment, offering a novel approach to enhancing insulin sensitivity and managing glucose levels through the modulation of key molecular pathways. Further research is needed to translate these findings into clinical practice.

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., Competing Interests: Conflict of Interest: The authors declare no conflicts of interest. “The study was conducted in accordance with the Declaration of Helsinki, and approved by the Institutional Review Board (or Ethics Committee) of Yarmouk University (39/2022). Informed consent was obtained from all subjects involved in the study. Written informed consent has been obtained from the patient(s) to publish this paper. Data is available from the corresponding author and can be provided upon request., (© 2024 the Author(s), licensee AIMS Press.)

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.

Hypertension, a major contributor to cardiovascular morbidity, is closely linked to amino acid metabolism. Amino acids, particularly branched-chain amino acids (BCAAs) and aromatic amino acids (AAAs), may play pivotal roles in the pathogenesis and potential management of hypertension. This review investigated the relationships between amino acid profiles, specifically BCAAs and AAAs, and hypertension, and examined their potential as diagnostic and therapeutic targets. An in-depth analysis was conducted on studies highlighting the associations of specific amino acids such as arginine, glycine, proline, glutamine, and the BCAAs and AAAs with hypertension. BCAAs and AAAs, alongside other amino acids like arginine, glycine, and proline, showed significant correlations with hypertension. These amino acids influence multiple pathways including nitric oxide synthesis, vascular remodeling, and neurotransmitter production, among others. Distinct amino acid profiles were discerned between hypertensive and non-hypertensive individuals. Amino acid profiling, particularly the levels of BCAAs and AAAs, offers promising avenues in the diagnostic and therapeutic strategies for hypertension. Future studies are crucial to confirm these findings and to delineate amino acid-based interventions for hypertension treatment., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

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., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Gammoh et al.)

Aim: Investigating a novel compound, DMPNP, for treating colitis in mice, a key issue in inflammatory bowel diseases (IBD). Methods: Mice with induced colitis received DMPNP (50, 100, 150 mg/kg) or sulfasalazine (SUL), evaluated via tissue assessment, Disease Activity Index (DAI), myeloperoxidase (MPO), nitric oxide (NO) levels and cytokine analysis. Results: DMPNP significantly reduced colitis symptoms, inflammation and oxidative stress at higher doses, with marked improvements in DAI, MPO, NO and cytokines, comparable to SUL results. Conclusion: DMPNP shows potent anti-inflammatory and immunomodulatory properties, indicating potential as an IBD therapeutic. Further clinical trials are suggested to validate these outcomes.

Objective: This study examined the prevalence and correlates of depression, anxiety, insomnia, and dysmenorrhea in stressed fingolimod-treated women with multiple sclerosis., Methods: This cross-sectional study recruited female patients diagnosed with multiple sclerosis and high stress scores from Al-Bashir Hospital in Jordan. Depression was assessed by the Patient Health Questionnaire (PHQ-9); anxiety by the Generalized Anxiety Disorder (GAD-7) scale; insomnia by the Insomnia Severity Index (ISI-A) scale; and dysmenorrhea severity by a measure assessing working ability, location, intensity, days of pain, and miscellaneous dysmenorrhea symptoms (WaLIDD)., Results: A total of 129 patients were recruited for the study. Severe depression was reported in 55.8%, severe anxiety in 62.0%, severe insomnia in 36.4%, and severe dysmenorrhea in 23.3%. Multivariate analyses revealed that depressive symptoms were associated with dysmenorrhea (OR = 3.55, 95% CI = 1.56-8.12, p = 0.003); anxiety symptoms with "not using dysmenorrhea analgesics" (OR = 2.74, 95% CI = 1.16-6.46, p = 0.02) and dysmenorrhea symptoms (OR = 4.74, 95% CI = 1.94-11.59, p = 0.001); insomnia symptoms with age above 30 years (OR = 4.34, 95% CI = 1.64-11.51, p = 0.003); and dysmenorrhea symptoms with the presence of chronic diseases (OR = 4.21, 95% CI = 1.28-13.92, p = 0.02), anxiety symptoms (OR = 3.03, 95% CI = 1.18-7.73, p = 0.02), and insomnia symptoms (OR = 3.00, 95% CI = 1.18-7.64, p = 0.02)., Conclusion: Stressed women with multiple sclerosis in Jordan experience high rates of depression, anxiety, insomnia, and dysmenorrhea. Characteristics related to these conditions may help clinicians to identify those at risk. Longitudinal studies are needed to determine the causal nature of these associations., Competing Interests: Declaration of conflicting interestThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Oxidative stress and inflammation are implicated in depression. While selective serotonin reuptake inhibitors (SSRIs) like escitalopram are commonly prescribed as first-line treatments, their inconsistent efficacy and delayed onset of action necessitates the exploration of adjunctive therapies. Isorhamnetin, a flavonol, has shown antioxidant and anti-inflammatory properties that makes exploring its antidepressant effect attractive. This study aims to investigate the adjuvant potential of isorhamnetin in combination with escitalopram to enhance its antidepressant efficacy in a lipopolysaccharide (LPS)-induced depression model using Swiss albino mice. Behavioral paradigms, such as the forced swim test and open field test, were employed to assess depressive symptoms, locomotion, and sedation. Additionally, enzyme-linked immunosorbent assays were utilized to measure Nrf2, BDNF, HO-1, NO, and IL-6 levels in the prefrontal cortex and hippocampus. The results demonstrate that isorhamnetin significantly improves the antidepressant response of escitalopram, as evidenced by reduced floating time in the forced swim test. Moreover, isorhamnetin enhanced antidepressant effects of escitalopram and effectively restored depleted levels of Nrf2, BDNF, and HO-1 in the cortex caused by LPS-induced depression. Isorhamnetin shows promise in enhancing the efficacy of conventional antidepressant therapy through antioxidant and anti-inflammatory effects.

The aim of this study was to investigate the potential antidepressant and anxiolytic effects of vitamin C and vitamin D in a stress-induced mouse model of depression, while also exploring the association between these effects and the levels of circulating NOx, periostin, and FKBPL. Our findings revealed that both vitamin C and vitamin D exhibited comparable antidepressant effects to escitalopram, a commonly used antidepressant, without demonstrating any anxiolytic effects. The antidepressant properties of vitamin C and vitamin D were linked to the normalization of Nox and FKBPL levels, while the levels of periostin showed no significant correlation. These results are consistent with previous research, indicating that the antidepressant effects of vitamin C and vitamin D may be attributed to their antioxidant and anti-inflammatory properties, as well as their modulation of neurotransmission and norepinephrine release. Additionally, our study uncovered elevated levels of periostin in stress-induced depression, which were only restored to normal levels by escitalopram, suggesting a potential role for periostin in mood disorders. Furthermore, FKBPL and NOx levels were increased in stress-induced depression and normalized by treatment with vitamin C, vitamin D, and escitalopram, indicating their involvement in the stress response and gene expression regulation. However, it is important to acknowledge certain limitations of our research, such as the use of a single depression induction model and limited dosing regimens. Future investigations should focus on examining these markers in specific brain regions, such as the hippocampus and prefrontal cortex, to gain a more comprehensive understanding of their potential implications for depression. Overall, our findings suggest that vitamin C, vitamin D, and escitalopram may possess antidepressant properties mediated by NOx and FKBPL levels, while emphasizing the potential significance of periostin in the context of depression.

Background: Little is known about the association between antihypertensive drugs with mental health outcomes. We examined the association between the antihypertensive classes and other clinical patient features with symptoms of depression, anxiety, insomnia, and Post-Traumatic Stress Disorder (PTSD) in a cohort of Syrian war refugees with stress and hypertension residing in Jordan., Methods: This cross-sectional study recruited hypertensive Syrian refugees with stress. Depression severity was assessed using the Patient Health Questionnaire-9, anxiety was measured by The General Anxiety Disorder-7, the Insomnia Severity Index was used to evaluate sleep quality and PTSD was measured using Davidson Trauma Scale. To investigate the association between the different classes of antihypertensive medication and mental health outcomes we used multivariable regression models., Results: Of the 492 participants, 251 were men (51%), 234 (47.6%) were on β-blockers, 141 (28.7%) on diuretics, and 209 (42.5%) on Angiotensin Converting Enzyme Inhibitors (ACEIs)/Angiotensin Receptor Blockers (ARBs). Although the multivariate regression revealed the different classes of antihypertensives are not associated with mental health symptoms, however, physical activity is associated with lower adjusted odds for symptoms of depression (0.68 (0.46-0.99), p = 0.04), anxiety (0.60 (0.42-0.85),p = 0.005), insomnia (0.63 (0.44-0.91),p = 0.01) and dyslipidemia (3.48(0.29-6.69),p = 0.03) is associated with higher PTSD symptoms., Limitations: The study subjects were not assessed for psychiatric diagnoses clinically. Further, we used a cross-sectional design that does not allow to measure longitudinal changes., Conclusions: The association between antihypertensive drugs and mental health symptoms was not evident in the present study. Follow-up future studies are required., Competing Interests: Declaration of Competing Interest None, (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Lysionotin, a natural flavonoid extracted from Lysionotus pauciflorus Maxim (Gesneriaceae), has several pharmacological effects including anti-bacterial, anti-hypertensive and anti-inflammatory effects. However, its analgesic effect has not been investigated. This study aimed to assess the antinociceptive activity of lysionotin using chemically and thermally induced nociception in a mouse model., Methods: The antinociceptive effects of various lysionotin doses (50, 100, 150, and 200 μg/kg) were assessed in mice using the acetic acid-induced writhing test, hot plate test, and formalin-induced paw licking assay. The effects were compared to those of mice treated with acetylsalicylic acid or morphine in the presence or absence of naloxone (an opioid receptor antagonist). Capsaicin- and glutamate-induced paw licking tests were also used to evaluate the involvement of the vanilloid and glutamatergic systems, respectively., Results: Lysionotin produced significant dose-dependent inhibition of nociceptive behavior in the acetic acid-induced writhing test, showing 60% inhibition at a dose of 200 μg/kg. Lysionotin also caused a significant increase in the latency period in response to the hot plate test (76.4% at 200 μg/kg), and significantly inhibited both the neurogenic and inflammatory phases in the formalin-induced paw licking test. Naloxone significantly reverses the effect of lysionotin in both hot plate test and formalin-induced paw licking test. Moreover, lysionotin significantly inhibited the neurogenic nociception induced by intraplantar injections of glutamate and capsaicin (57% and 67.2%, respectively at a dose of 200 μg/kg). Thus, lysionotin exhibited peripheral and central antinociception through the modulation of vanilloid receptors, opioid receptors, and the glutamatergic system., Conclusion: Lysionotin possesses antinociceptive activity on adult mice that is mediated through both central and peripheral pathways., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this article., (© 2023 The Authors.)

Background and objectives : Community pharmacists play an important role in ensuring the patient's adherence to medications, thus achieving therapeutic outcomes. The present study had two aims: to measure the extent of knowledge that community pharmacists had about psychotropic medications and to determine the factors associated with higher knowledge scores. Methods: A cross-sectional design was employed, using a structured online questionnaire. The study instrument assessed demographics, general practice characteristics related to psychotropics and a battery of factual questions that assessed the knowledge of pharmacists about psychotropic medications using closed-ended responses. A total knowledge score consisting of the sum of correct responses was calculated; the passing score was 75%. A total of 676 pharmacists completed the survey. Results: Only 20% passed the threshold score (75%) for the factual knowledge questions, and only (11.0%) were very comfortable with their knowledge of psychotropic agents. A total of 49.0% of the respondents felt that they had been adequately trained to counsel patients on psychotropic agents. According to the regression model, pharmacists who reported higher knowledge were more experienced (0.63, (0.26-1.0), p < 0.001), reported studying the topic in the pharmacy school (0.77 (0.27-1.26), p = 0.002) holding a Doctor of Pharmacy (Pharm D) degree (0.24 (0.05-0.43), p = 0.01), and reported a higher perceived knowledge (0.29 (0.01-0.38), p = 0.038). Conclusion: Community pharmacists reported poor knowledge of psychotropic medications, and continuous medical and professional education programs are mandatory.

Cirsimaritin is a dimethoxy flavon that has different biological activities such as antiproliferative, antimicrobial, and antioxidant activities. This study aims to investigate the anti-diabetic effects of cirsimaritin in a high-fat diet and streptozotocin-(HFD/STZ)-induced rat model of type 2 diabetes mellitus (T2D). Rats were fed HFD, followed by a single low dose of STZ (40 mg/kg). HFD/STZ diabetic rats were treated orally with cirsimaritin (50 mg/kg) or metformin (200 mg/kg) for 10 days before terminating the experiment and collecting plasma, soleus muscle, adipose tissue, and liver for further downstream analysis. Cirsimaritin reduced the elevated levels of serum glucose in diabetic rats compared to the vehicle control group ( p < 0.001). Cirsimaritin abrogated the increase in serum insulin in the treated diabetic group compared to the vehicle control rats ( p < 0.01). The homeostasis model assessment of insulin resistance (HOMA-IR) was decreased in the diabetic rats treated with cirsimaritin compared to the vehicle controls. The skeletal muscle and adipose tissue protein contents of GLUT4 ( p < 0.01 and p < 0.05, respectively) and pAMPK-α1 ( p < 0.05) were upregulated following treatment with cirsimaritin. Cirsimaritin was able to upregulate GLUT2 and AMPK protein expression in the liver ( p < 0.01, <0.05, respectively). LDL, triglyceride, and cholesterol were reduced in diabetic rats treated with cirsimaritin compared to the vehicle controls ( p < 0.001). Cirsimaritin reduced MDA, and IL-6 levels ( p < 0.001), increased GSH levels ( p < 0.001), and reduced GSSG levels ( p < 0.001) in diabetic rats compared to the vehicle control. Cirsimaritin could represent a promising therapeutic agent to treat T2D.