Sex-dependent alterations of inflammatory factors, oxidative stress, and histopathology of the brain-gut axis in a VPA-induced autistic-like model of rats.

INTRODUCTION: In this study, we aimed to investigate the inflammatory factors, oxidative stress, and histopathological consequences of the brain-gut axis in male and female rats prenatally exposed to VPA. METHODS: Pregnant Wistar rats were randomly divided into two groups. The animals received saline, and valproic acid (VPA) (600 mg/kg, i.p.) on embryonic day 12.5 (E12.5). All offspring were weaned on postnatal day 21, and the experiments were done in male and female rats on day 60. The brain and intestine tissues were extracted to assess histopathology, inflammation, and oxidative stress. RESULTS: An increase of interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) and a decrease of interleukin-10 (IL-10) were observed in the two sexes and two tissues of the autistic rats. In the VPA-exposed animals, malondialdehyde (MDA) and protein carbonyl (PC) increased in the brain of both sexes and the intestines of only the males. The total antioxidant capacity (TAC), superoxide dismutase (SOD), and catalase (CAT) significantly decreased in both tissues of male and female autistic groups. Histopathological evaluation showed that the %apoptosis of the cortex in the autistic male and female groups was more than in controls whereas this parameter in the CA1 and CA3 was significant only in the male rats. In the intestine, histopathologic changes were seen only in the male autistic animals. CONCLUSION: The inflammatory and antioxidant factors were in line in the brain-gut axis in male and female rats prenatally exposed to VPA. Histopathological consequences were more significant in the VPA-exposed male animals.

Alnustone: A review of its sources, pharmacology, and pharmacokinetics .

Alnustone (4(E)-,6(E)-1,7-Diphenyl-hepta-4,6-dien-3-one) is a non-phenolic natural diarylheptanoid, which was first isolated and identified from the male flower of Alnus pendula (Betulaceae). It can also be isolated from Curcuma xanthorrhiza Roxb (Zingiberaceae) rhizomes and Alpinia katsumadai Hayata (Zingiberaceae) seeds. It was first synthesized through a five-step process from ß-phenyl propionyl chloride. In later years, new methods for synthesizing Alnustone were designed and performed with different yields. Due to the various therapeutic effects exhibited by alnustone like other diarylheptanoids, its biological activities such as antioxidant, antibacterial, and anti-inflammatory properties have been the subject of many studies. This article has reviewed different aspects of this valuable natural compound, including its natural and synthetic sources, therapeutic effects, and pharmacokinetics as a potential future therapeutic agent.

Sericin alleviates motor dysfunction by modulating inflammation and TrkB/BDNF signaling pathway in the rotenone-induced Parkinson's disease model.

BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the degeneration of nigrostriatal dopaminergic neurons and movement impairment. Based on theories, neuroinflammatory processes may be vital in the etiology of PD and other neurodegenerative diseases. Reports show that rotenone has neurotoxic, inflammatory, and motor impairment effects in PD. Sericin is a natural polymer with effective properties, such as neuroprotective and anti-inflammatory. Therefore, this study aimed to examine the effects of sericin administration on motor dysfunction by modulating inflammation and tyrosine kinase B/brain-derived neurotrophic factor (TrkB/BDNF) pathway in the rotenone-induced PD model. METHODS: Wistar male rats (3-months-old) were treated with rotenone (2 mg/kg every 48 h for 30 days) to induce a rotenone-induced PD model. Also, sericin was administered orally at dose of 200 mg/kg every 48 h for 30 days. Rotarod and bar tests were performed for motor dysfunction. The protein levels of BDNF, c-fos, TrkB, tumor necrosis factor- α (TNF-α), interleukin-6 (IL-6) and catalase activity were evaluated in the striatum area. RESULTS: Results showed that sericin increased latent time in the rotarod test and decreased the time staying on the pole in the bar test compared to the PD group (P < 0.001 for both tests). Moreover, sericin treatments decreased TNF-α (P < 0.001) and IL-6 (P < 0.001) concentration levels and enhanced the levels of BDNF (P < 0.001), c-fos (P < 0.001), TrkB (P < 0.001) proteins and catalase activity (P < 0.05) in the striatum area compared to the PD group. CONCLUSION: These results support a protective benefit of sericin therapy in a rotenone-induced PD paradigm by reducing motor impairment, inflammatory response, and disruption of the TrkB/BDNF signaling pathway.

Effect of the Sargassum angustifolium Extract on Methamphetamine-Induced Cytotoxicity in SH-SY5Y Cells.

This study aimed to assess the effect of the Sargassum angustifolium extract in methamphetamine-induced SH-SY5Y cells death. The brown algae S. angustifolium was extracted with 80% ethanol. The SH-SY5Y cells were treated with different concentrations of methamphetamine to measure IC50.. The MTT test was used to assess the toxic effect of the S. angustifolium extract in SH-SY5Y cells. SH-SY5Y cells' survival was measured while cells were treated with different concentrations of methamphetamine and S. angustifolium extract simultaneously. A specific kit measured intracellular ROS levels. Western blot analysis evaluated the expression of cytochrome C and Bax/Bcl2 ratio. The results showed that 5 mM methamphetamine approximately killed 50% of the cells, so it is considered IC50. The MTT test showed no toxicity effect for the S. angustifolium extract. 80, 160, 320, and 640 µg/ml of S. angustifolium extract prevented the occurrence of methamphetamine toxic effects in SH-SY5Y cells after 24 hours. Moreover, the S. angustifolium extract decreased ROS levels and cytochrome C release and reduced BaX/Bcl2 ratio in cells treated by methamphetamine. On the whole, it seems that the S. angustifolium hydroalcoholic extract has the potential to increase cell survival through in vitro antioxidant and antiapoptotic activities.

Geospatial analysis of cesarean section in Iran (2016-2020): exploring clustered patterns and measuring spatial interactions of available health services.

BACKGROUND: The lives of babies and mothers are at risk due to the uneven distribution of healthcare facilities required for emergency cesarean sections (CS). However, CS without medical indications might cause complications for mothers and babies, which is a global health problem. Identifying spatiotemporal variations of CS rates in each geographical area could provide helpful information to understand the status of using CS services. METHODS: This cross-sectional study explored spatiotemporal patterns of CS in northeast Iran from 2016 to 2020. Space-time scan statistics and spatial interaction analysis were conducted using geographical information systems to visualize and explore patterns of CS services. RESULTS: The temporal analysis identified 2017 and 2018 as the statistically significant high clustered times in terms of CS rate. Five purely spatial clusters were identified that were distributed heterogeneously in the study region and included 14 counties. The spatiotemporal analysis identified four clusters that included 13 counties as high-rate areas in different periods. According to spatial interaction analysis, there was a solid spatial concentration of hospital facilities in the political center of the study area. Moreover, a high degree of inequity was observed in spatial accessibility to CS hospitals in the study area. CONCLUSIONS: CS Spatiotemporal clusters in the study area reveal that CS use in different counties among women of childbearing age is significantly different in terms of location and time. This difference might be studied in future research to identify any overutilization of CS or lack of appropriate CS in clustered counties, as both put women at risk. Hospital capacity and distance from population centers to hospitals might play an essential role in CS rate variations and spatial interactions among people and CS facilities. As a result, some healthcare strategies, e.g., building new hospitals and empowering the existing local hospitals to perform CS in areas out of service, might be developed to decline spatial inequity.

The role of dopamine D2-like receptors in a "depotentiation-like effect" of deep brain stimulation in kindled rats.

The mechanisms involved in the anti-seizure effects of low-frequency stimulation (LFS) have not been completely determined. However, Gi-protein-coupled receptors, including D2-like receptors, may have a role in mediating these effects. In the present study, the role of D2-like receptors in LFS' anti-seizure action was investigated. Rats were kindled with semi-rapid (6 stimulations per day), electrical stimulation of the hippocampal CA1 area. In LFS-treated groups, subjects received four trials of LFS at 5 min, 6 h, 24 h, and 30 h following the last kindling stimulation. Each LFS set occurred at 5 min intervals, and consisted of 4 trains. Each train contained 200, 0/1 ms long, monophasic square wave pulses at 1 Hz. Haloperidol (D2-like receptors antagonist, 2 µm) and/or bromocriptine (D2-like receptors agonist 2 µg/µlit) were microinjected into the lateral ventricle immediately after the last kindling, before applying LFS. Obtained results showed that applying LFS in fully-kindled subjects led to a depotentiation-like decrease in kindling-induced potentiation and reduced the amplitude and rise slope of excitatory and inhibitory post-synaptic currents in whole-cell recordings from CA1 pyramidal neurons. In addition, LFS restored the kindling-induced, spatial learning and memory impairments in the Barnes maze test. A D2-like receptor antagonist inhibited these effects of LFS, while a D2-like receptor agonist mimicked these effects. In conclusion, a depotentiation-like mechanism may be involved in restoring LFS' effects on learning and memory, and synaptic plasticity. These effects depend on D2-like receptors activity.

Antifungal effects of Ziziphora tenuior, Lavandula angustifolia, Cuminum cyminum essential oils against clinical isolates of Candida albicans from women suffering from vulvovaginal candidiasis / Efecto antifungico de los aceites esenciales de Ziziphora tenuior, Lavandula angustifolia y Cuminum cyminum contra aislados clínicos de Candida albicans de mujeres que sufren de candidiasis vulvovaginal

Candida sp. especially C. albicans is the main cause of candidiasis in women in reproductive ages. The prevalence of drug resistant C. albicans along with adverse effects of current treatments have encouraged the scientists to research on medicinal plant's essential oils. The aim of this study was to evaluate the potential effects of Ziziphora tenuior, Lavandula angustifolia, Cuminum cyminum essential oils against clinical isolates of C. albicans, which were isolated from women with vulvovaginal candidiasis. The anti-candidal effects of these commercial essential oils were screened against these clinical isolates (n=80) by disc diffusion and micro-broth dilution assays. The means of inhibition zone diameters, MIC and MFCs were reported for each essential oil. Also, the capability of fungal strain for biofilm formation in comparison with C. albicans ATCC 10231 were determined. The anti-biofilm effects of essential oils against 11 biofilm producing strains of C. albicans were determined. The results showed C. cyminum and Z. tenuior essential oils had the best anti-candidal effects, while the best biofilm killing effects was for L. angustifolia essential oil. C. cyminum and Z. tenuior essential oils can be formulated for more evaluations in preclinical and clinical studies.

Candida sp., especialmente C. albicans, es la principal causa de candidiasis en mujeres en edad reproductiva. La aparición de resistencia a los antifungicos de C. albicans, junto con el riesgo de efectos adversos de los tratamientos actuales, ha llevado a los científicos a buscar alternativas en los aceites esenciales derivados de plantas. Los objetivos del estudio fueron evaluar los efectos potenciales de los aceites esenciales de Ziziphora tenuior, Lavandula angustifolia, Cuminum cyminum, contra aislados clínicos de C. albicans, obtenidos de mujeres con candidiasis vulvovaginal. Los efectos anti-Candida de estos aceites esenciales comerciales fueron probados contra estos aislados clínicos (n=80) por difusión en disco y ensayos de microdilución. Se obtuvo el promedio de diámetro de inhibición, MIC y MFCs para cada aceite esencial. También se comparó la capacidad de formación de biopelículas de 11 cepas de C. albicans de cada aislado frente a la cepa de referencia C. albicans ATCC 10231 y la capacidad de cada aceite esencial para evitar la formación de biopelículas. Los resultados muestran que los aceites esenciales de C. cyminum y Z. tenuior tuvieron la mejor actividad anti-Candida, mientras que los mejores efectos para destruir biopelículas se obtuvieron con los aceites esenciales de L. angustifolia. Los aceites esenciales de C. cyminum y Z. tenuior ameritan tener mayores evaluaciones preclínicas y clínicas.

A randomized controlled clinical trial evaluating quality of life when using a simple acupressure protocol in women with primary dysmenorrhea.

OBJECTIVE: To evaluate a simple acupressure protocol in LIV3 and LI4 acupoints in women with primary dysmenorrhea. METHODS: This paper reports a randomized, single blinded clinical trial. 90 young women with dysmenorrhea were recruited to three groups to receive 20min acupressure every day in either LIV3 or LI4, or placebo points. Acupressure was timed five days before menstruation for three successive menstrual cycles. On menstruation, each participant completed the Wong Baker faces pain scale, and the quality of life short form -12 (QOL SF-12). RESULTS: Intensity and duration of pain between the three groups in the second and third cycles during the intervention (p<0.05) differed significantly. Significant differences were seen in all domains of QOL except for mental health (p=0.4), general health (p=0.7) and mental subscale component (p=0.12) in the second cycle, and mental health (p=0.9), and mental subscale component (p=0.14) in the third cycle. CONCLUSION: Performing the simple acupressure protocol is an effective method to decrease the intensity and duration of dysmenorrhea, and improve the QOL. Registration ID in IRCT: IRCT2016052428038N1.