Anticonvulsant effect of melatonin through ATP-sensitive channels in mice

Melatonin is a neurohormone secreted principally by the pineal gland. This molecule has various pharmacological properties including improving immune system, prevent cancer, anti-aging, and anti-oxidant effects. The anticonvulsant effects of melatonin have been proved by previous studies. Adenosine triphosphate (ATP)-sensitive potassium (K_ATP) channels are considered as an important target in the seizure modulation. The aim of the present study was to investigate the anticonvulsant effect of melatonin in pentylenetetrazole (PTZ)-induced seizures in mice, focusing on its ability to regulate K_ATP channels. Acute intraperitoneal administration of melatonin (40 and 80 mg/kg) increased clonic seizure threshold induced by intravenous administration of PTZ. Melatonin (40 and 80 mg/kg) increased the latency of clonic seizure and reduced its frequency in mice receiving an intraperitoneal injection of PTZ. Administration of glibenclamide, a K_ATP channels blocker, before intravenous injection of PTZ reduced melatonin anticonvulsant effect. Diazoxide and cromakalim, as K_ATP channels openers, increased antiseizure effect of melatonin in PTZ model of seizures. These findings suggest that the antiseizure effect of melatonin probably is gained through increasing the opening of K_ATP channels.     

Evolutionary puzzle of Toxoplasma gondii with suicidal ideation and suicide attempts: An updated systematic review and meta‐analysis

The World Health Organization has reported an annual global suicide rate of 14.5 per 100,000 people. On the other hand, it is estimated that approximately one‐third of the global population are infected with Toxoplasma gondii (T. gondii) parasite. It is widely assumed that microbial pathogens, such as T. gondii, are probably associated with affective and behavioural modulation. The present article aimed to assess the proposed role of toxoplasmosis in raising the risk of suicidal ideation (SI) and suicide attempts (SA) using the available epidemiological data. Seven major electronic databases and the Internet search engine Google were searched for all the studies published between the 1st of January 1950 and 31st of October 2019. The heterogeneity and the risk of bias within and across studies were assessed. Following data extraction, pooled odds ratios (ORs) with 95% confidence interval (CI) across studies were calculated using the random‐effects models. A total number of 9,696 articles were screened and 27 studies were regarded as eligible in our systematic review (SI with five papers and 22 papers on SA). A significant association was detected between antibodies against T. gondii with TA (ORs = 1.57; 95% confidence interval [CI] 1.23–2.00, p = .000). Exploration of the association between T. gondii and SA yielded a positive effect of seropositivity for IgG antibodies but not IgM. Despite the limited number of studies, a statistical association was detected between suicidal behaviours and infection with latent T. gondii.     

Complementary and alternative medicine use among ischemic stroke survivors in Jeddah,Saudi Arabia

Objectives:To determine the prevalence and pattern of complementary and alternative medicine (CAM) use and the CAM types used by stroke patients in Jeddah, Kingdom of Saudi Arabia.Methods:This cross-sectional study included 152 ischemic stroke survivors who visited King Fahad Hospital, Jeddah, Kingdom of Saudi Arabia, between January 2018 and December 2019. Phone-based and face-to-face surveys were conducted. Data on the patients’ demographic characteristics, their use of CAM, and their pattern of CAM use were gatheredResults:Ninety (59.2%) stroke patients used CAM, mainly cauterization (29.61%) and Quran recitation by a religious sheik (28.95%). Most of the patients (72.22%) used CAM post-hospitalization and within less than one month from stroke onset (62.22%). A minority (6.67%) of the patients stopped their medication while on CAM. Some patients (25.56% to 31.11%) discussed with their physician their use of CAM. The CAM users reported a subjective improvement in their physical weakness (45.6%) and psychological wellbeing (62.2%). The patients learned about CAM mainly from their relatives and friends (96.7%), and the most common reason for their CAM use was their belief in this intervention (42.22%).Conclusion:The CAM use was prevalent among our cohort of Saudi ischemic stroke patients, and cauterization and Quran recitation were the most commonly used CAM interventions. An effective communication was lacking between the medical professionals and the stroke patients as regards CAM use despite the interest of the patients in this intervention.

Over the past 2 decades, the burden of stroke has increased globally.1 Stroke is the second leading cause of morbidity and mortality; the annual incidence of stroke is approximately 15 million, and over 5.5 million stroke-related deaths occur annually.2–4 Also, the prevalence of the modifiable risk factors of stroke is increasing, and the burden of stroke increases with the aging of the population.5 Adults aged >25 years have an estimated lifetime stroke risk of 24.9%.6 Despite the advancements in acute stroke care, highly effective treatments for the later phases of stroke are lacking. This shortcoming in the stroke care leads patients and their relatives to seek other treatment options, such as complementary and alternative medicine (CAM).7 The CAM is defined by the United State of America National Institutes of Health as “a group of diverse medical and health care systems, practices, and products that are not generally considered conventional medicine.”8 The CAM has been used for a long time now,9 and people widely practice CAM for various health conditions, such as cancer, epilepsy, multiple sclerosis, infertility, surgical procedure, dermatological conditions, hypertension, pain, and other types of illnesses.1,9–11 The prevalence of CAM use varies by country. For example, the prevalence of CAM use is 82% in the United States,12 61% in Australia,13 51% in Malaysia,14 and 61% in Turkey.15 Religion, cultures, and values influence the types and patterns of its use.16 People in Western countries practice herbal medicine, reflexology, aromatherapy, massage, osteopathy, meditation, and spiritual healing;10,17–19 by contrast, those in Asian countries such as China, India, and Taiwan commonly use therapies such as traditional Chinese medicine, Ayurvedic medicine, physical exercises, acupuncture, Tai Chi, yoga, and homeopathy.20–23 In Saudi Arabia, different types of CAM are used including the Quran recitation therapy, honey consumption, plant-based traditional medicine (e.g., Murrah and black seed consumption), cupping (“Hojamah”), and cauterization (“skin ironing”)9,24–27Research highlighted that aside from their potential benefits, some types of CAM have many side effects and potential toxicities, and patients are commonly unaware of these possible dangers.28 One study reported 2 cases wherein the cauterization led to severe complications, such as skin burn.29 Another study that investigated the components of herbal medicines in Saudi Arabia indicated that 15.7% of the tested samples contain toxic amounts of heavy metals, including arsenic and mercury.30 Despite the potential risk of many CAM interventions, it has been noted that many patients do not inform their physicians about their practice of CAM.31Stroke patients in many countries, including the United States (30.6%–46%)32,33 and South Korea (54%), use CAM.34 In Riyadh, Saudi Arabia, 67% of patients with neurological problems use CAM,9 and most of them use cupping (Hojamah) (45.4%), herbal medicine (42.3%), cauterization (33.7%), and Quran recitation (20.4%).9 However, no available study has analyzed the use of CAM particularly by stroke patients in Saudi Arabia. Thus, this study aimed to determine the prevalence and pattern of CAM use and the types of CAM being practiced by ischemic stroke patients relation to their demographic data.     

Toll‐like receptors as novel therapeutic targets for herpes simplex virus infection

Seropositivity for HSV reaches more than 70% within the world population, and yet no approved vaccine exists. While HSV1 is responsible for keratitis, encephalitis, and labialis, HSV2 carriers have a high susceptibility to other STD infections, such as HIV. Induction of antiviral innate immune responses upon infection depends on a family of pattern recognition receptors called Toll‐like receptors (TLR). TLRs bridge innate and adaptive immunity by sensing virus infection and activating antiviral immune responses. HSV adopts smart tricks to evade innate immunity and can also manipulate TLR signaling to evade the immune system or even confer destructive effects in favor of virus replication. Here, we review mechanisms by which HSV can trick TLR signaling to impair innate immunity. Then, we analyze the role of HSV‐mediated molecular cues, in particular, NF‐κB signaling, in promoting protective versus destructive effects of TLRs. Finally, TLR‐based therapeutic opportunities with the goal of preventing or treating HSV infection will be discussed.     

Effects of upper-body resistance exercise training on serum nesfatin-1 level,insulin resistance,and body composition in obese paraplegic men

Background

As a recently discovered adipokine, nesfatin-1 is conducive to insulin sensitivity, lipid profile, energy balance, and probably obesity.

Soy,Soy Isoflavones,and Protein Intake in Relation to Mortality from All Causes,Cancers, and Cardiovascular Diseases: A Systematic Review and Dose–Response Meta-Analysis of Prospective Cohort Studies

ObjectiveWe conducted a systematic review and dose–response meta-analysis of prospective studies to summarize findings on the associations between intakes of soy, soy isoflavones, and soy protein and risk of mortality from all causes, cancers, and cardiovascular diseases.MethodsOnline databases were systematically searched to identify relevant articles published earlier than May 2018. We applied restricted cubic splines using random-effects analysis to assess dose–response associations. Between-study heterogeneity was assessed by I² value and Cochrane Q test. Potential publication bias was assessed by visual inspection of funnel plots and Begg regression test.ResultsIn total, 23 prospective studies with an overall sample size of 330,826 participants were included in the current systematic review and the meta-analysis. Soy/soy products consumption was inversely associated with deaths from cancers (pooled relative risk 0.88, 95% CI 0.79 to 0.99; P=0.03; I²=47.1%, 95% CI 0.0% to 75.4%) and cardiovascular diseases (pooled effect size: 0.85, 95% CI 0.72 to 0.99; P=0.04; I²=50.0%, 95% CI 0.0% to 77.6%). Such significant associations were also observed for all-cause mortality in some subgroups of the included studies, particularly those with higher quality. In addition, higher intake of soy was associated with decreased risk of mortality from gastric, colorectal, and lung cancers as well as ischemic cardiovascular diseases. Participants in the highest category of dietary soy isoflavones intake had a 10% lower risk of all-cause mortality compared with those in the lowest category. We also found that a 10-mg/day increase in intake of soy isoflavones was associated with 7% and 9% decreased risk of mortality from all cancers and also breast cancer respectively. Furthermore, a 12% reduction in breast cancer death was indicated for each 5-g/day increase in consumption of soy protein. However, intake of soy protein was not significantly associated with all-cause and cardiovascular diseases mortality.ConclusionsSoy and its isoflavones may favorably influence risk of mortality. In addition, soy protein intake was associated with a decreased risk in the mortality of breast cancer. Our findings may support the current recommendations to increase intake of soy for greater longevity.     

Therapeutic effects of kaempferol affecting autophagy and endoplasmic reticulum stress

Regulated cell death (RCD) guarantees to preserve organismal homeostasis. Apoptosis and autophagy are two major arms of RCD, while endoplasmic reticulum (ER) as a crucial organelle involved in proteostasis, promotes cells toward autophagy and apoptosis. Alteration in ER stress and autophagy machinery is responsible for a great number of diseases. Therefore, targeting those pathways appears to be beneficial in the treatment of relevant diseases. Meantime, among the traditional herb medicine, kaempferol as a flavonoid seems to be promising to modulate ER stress and autophagy and exhibits protective effects on malfunctioning cells. There are some reports indicating the capability of kaempferol in affecting autophagy and ER stress. In brief, kaempferol modulates autophagy in noncancerous cells to protect cells against malfunction, while it induces cell mortality derived from autophagy through the elevation of p‐AMP‐activated protein kinase, light chain‐3‐II, autophagy‐related geness, and Beclin‐1 in cancer cells. Noteworthy, kaempferol enhances cell survival through C/EBP homologous protein (CHOP) suppression and GRP78 increment in noncancerous cells, while it enhances cell mortality through the induction of unfolding protein response and CHOP increment in cancer cells. In this review, we discuss how kaempferol modulates autophagy and ER stress in noncancer and cancer cells to expand our knowledge of new pharmacological compounds for the treatment of associated diseases.