Role of histone deacetylases and sirtuins in the ischaemic stroke: a protocol for a systematic review and meta-analysis of animal studies.

BACKGROUND: Stroke is a major cause of global mortality and disability. Currently, the treatment of acute ischaemic stroke through reperfusion has posed several challenges, raising the need for complementary options to protect the ischaemic penumbra. Recent investigations have indicated that certain epigenetic factors, specifically, histone deacetylases (HDACs) and sirtuins, can be promising for ischaemic stroke therapy, with recent studies suggesting that inhibitors of HDACs or sirtuins may provide neuronal protection after ischaemic stroke. However, the impact of specific HDAC/sirtuin isoforms on the survival of neuronal cells following stroke is still uncertain. This study aims to provide a comprehensive overview of the function of HDACs and their modulators in the treatment of acute ischaemic stroke. METHODS: This systematic review and meta-analysis will encompass animal intervention studies that explore the efficacy of modulation of HDACs and sirtuins in the acute phase of ischaemic stroke. The review will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Electronic searches will be conducted in PubMed, Web of Science and Scopus, with subsequent screening by independent reviewers based on the established eligibility criteria. Methodological quality will be evaluated using the SYRCLE risk of bias tool. The primary outcomes will be infarct volume and functional response, with the secondary outcomes established a priori. Data pertaining to infarct volume will be used for random-effects meta-analysis. Additionally, a descriptive summary will be conducted for the functional response and secondary outcomes. DISCUSSION: No systematic review and meta-analysis on the treatment of ischaemic stroke through HDAC modulation has been conducted to date. A comprehensive analysis of the available literature on the relevant preclinical investigations can yield invaluable insights in discerning the most effective trials and in further standardisation of preclinical studies. SYSTEMATIC REVIEW REGISTRATION: This systematic review has been recorded in the International Prospective Register of Systematic Reviews (PROSPERO), with the assigned reference number: CRD42023381420.

The influence of climate change on the future distribution of two Thymus species in Iran: MaxEnt model-based prediction.

Within a few decades, the species habitat was reshaped at an alarming rate followed by climate change, leading to mass extinction, especially for sensitive species. Species distribution models (SDMs), which estimate both present and future species distribution, have been extensively developed to investigate the impacts of climate change on species distribution and assess habitat suitability. In the West Asia essential oils of T. daenensis and T. kotschyanus include high amounts of thymol and carvacrol and are commonly used as herbal tea, spice, flavoring agents and medicinal plants. Therefore, this study aimed to model these Thymus species in Iran using the MaxEnt model under two representative concentration pathways (RCP 4.5 and RCP 8.5) for the years 2050 and 2070. The findings revealed that the mean temperature of the warmest quarter (bio10) was the most significant variable affecting the distribution of T. daenensis. In the case of T. kotschyanus, slope percentage was the primary influencing factor. The MaxEnt modeling also demonstrated excellent performance, as indicated by all the Area Under the Curve (AUC) values exceeding 0.9. Moreover, based on the projections, the two mentioned species are expected to undergo negative area changes in the coming years. These results can serve as a valuable achievement for developing adaptive management strategies aimed at enhancing protection and sustainable utilization in the context of global climate change.

Habitat potential modelling and the effect of climate change on the current and future distribution of three Thymus species in Iran using MaxEnt.

Over the course of a few decades, climate change has caused a rapid and alarming reshaping of species habitats, resulting in mass extinction, particularly among sensitive species. In order to investigate the effects of climate change on species distribution and assess habitat suitability, researchers have developed species distribution models (SDMs) that estimate present and future species distribution. In West Asia, thyme species such as T. fedtschenkoi, T. pubescens, and T. transcaucasicus are rich in thymol and carvacrol, and are commonly used as herbal tea, spice, flavoring agents, and medicinal plants. This study aims to model the distribution of these Thymus species in Iran using the MaxEnt model under two representative concentration pathways (RCP 4.5 and RCP 8.5) for the years 2050 and 2070. The objective is to identify the crucial bioclimatic (n = 5), edaphic (n = 1), and topographic (n = 3) variables that influence their distribution and predict how their distribution might change under various climate scenarios. The findings reveal that the most significant variable affecting T. fedtschenkoi and T. pubescens is altitude, while soil organic carbon content is the primary factor influencing the distribution of T. transcaucasicus. The MaxEnt modeling demonstrates excellent performance, as indicated by all the area under the curve (AUC) values exceeding 0.9. Based on the projections, it is expected that these three thyme species will experience negative area changes in the coming years. These results can serve as a valuable tool for developing adaptive management strategies aimed at enhancing protection and sustainable utilization in the context of global climate change. Special attention should be given to conserving T. fedtschenkoi, T. pubescens, and T. transcaucasicus due to their significant habitat loss in the future.

Impact of climate change on the future distribution of three Ferulago species in Iran using the MaxEnt model.

The decline of habitats supporting medicinal plants is a consequence of climate change and human activities. In the Middle East, Ferulago angulata, Ferulago carduchorum, and Ferulago phialocarpa are widely recognized for their culinary, medicinal, and economic value. Therefore, this study models these Ferulago species in Iran using the MaxEnt model under two representative concentration pathways (RCP4.5 and RCP8.5) for 2050 and 2070. The objective was to identify the most important bioclimatic (n = 6), edaphic (n = 4), and topographic (n = 3) variables influencing their distribution and predict changes under various climate scenarios. Findings reveal slope percentage as the most significant variable for F. angulata and F. carduchorum, while solar radiation was the primary variable for F. phialocarpa. MaxEnt modeling demonstrated good to excellent performance, as indicated by all the area under the curve values exceeding 0.85. Projections suggest negative area changes for F. angulata and F. carduchorum (i.e., predictions under RCP4.5 for 2050 and 2070 indicate -34.0% and -37.8% for F. phialocarpa, and -0.3% and -6.2% for F. carduchorum; additionally, predictions under RCP 8.5 for 2050 and 2070 show -39.0% and -52.2% for F. phialocarpa, and -1.33% and -9.8% for F. carduchorum), while for F. phialocarpa, a potential habitat increase (i.e., predictions under RCP4.5 for 2050 and 2070 are 23.4% and 11.2%, and under RCP 8.5 for 2050 and 2070 are 64.4% and 42.1%) is anticipated. These insights guide adaptive management strategies, emphasizing conservation and sustainable use amid global climate change. Special attention should be paid to F. angulata and F. carduchorum due to anticipated habitat loss. Integr Environ Assess Manag 2024;00:1-14. © 2024 SETAC.

An Active Compound from the Pyrazine Family Induces Apoptosis by Targeting the Bax/Bcl2 and Survivin Expression in Chronic Myeloid Leukemia K562 Cells.

BACKGROUND: It has been established that pyrazine derivatives, which have widespread bioactivities, can effectively treat cancer. OBJECTIVES: In this study, we investigated the effects of 2-methoxy-5-(oxiran-2-ylmethyl) phenyl pyrazine-2- carboxylate (2-mOPP), a new pyrazine derivative, on proliferation, viability, and apoptosis induction in human leukemia K562 cells. METHODS: For this purpose, the K562 cells were treated with various concentrations (20-120 µM) of the 2-mOPP for 24-72 hours. Cell viability was determined by MTT growth inhibition assay. Apoptotic activity of 2-mOPP was investigated morphologically by Hoechst staining, cell surface expression assay of phosphatidylserine by Annexin-V/PI technique, as well as DNA fragmentation assay. The effect of 2-mOPP on the K562 cell cycle was studied by flow cytometry. To determine the impact of 2-mOPP on the expression of intrinsic apoptosis-related genes, Bcl2 (anti-apoptotic), Bax (pro-apoptotic), and Survivin genes expression levels were evaluated before and after treatment with 2-mOPP through Real-Time PCR analysis. RESULTS: The results revealed that 2-mOPP inhibited viability with IC50 of 25µM in 72 h. Morphological changes assessment by fluorescence microscopy, Annexin V/PI double staining by flow cytometry, and DNA ladders formation upon cell treatment with the 2-mOPP showed that this compound induces apoptosis at IC50 value. Cell cycle arrest was observed in the G0/G1 phase, and the sub-G1 cell population (the sign of apoptosis) increased in a time-dependent manner. Low expression levels of Bcl2 and Survivin in K562 cells were observed 24-72 h after treatment. Along with the down-regulation of Survivin and Bcl2, the expression of Bax was increased after treatment with 2-mOPP. CONCLUSION: These findings demonstrate that the new pyrazine derivative plays a crucial role in blocking the proliferation of the leukemic cells by inducing cell cycle arrest and apoptosis.

Predicting climate heating impacts on riverine fish species diversity in a biodiversity hotspot region.

Co-occurring biodiversity and global heating crises are systemic threats to life on Earth as we know it, especially in relatively rare freshwater ecosystems, such as in Iran. Future changes in the spatial distribution and richness of 131 riverine fish species were investigated at 1481 sites in Iran under optimistic and pessimistic climate heating scenarios for the 2050s and 2080s. We used maximum entropy modeling to predict species' potential distributions by hydrologic unit (HU) occupancy under current and future climate conditions through the use of nine environmental predictor variables. The most important variable determining fish occupancy was HU location, followed by elevation, climate variables, and slope. Thirty-seven species were predicted to decrease their potential habitat occupancy in all future scenarios. The southern Caspian HU faces the highest future species reductions followed by the western Zagros and northwestern Iran. These results can be used by managers to plan conservational strategies to ease the dispersal of species, especially those that are at the greatest risk of extinction or invasion and that are in rivers fragmented by dams.

Evaluation of scale development and its regeneration potency in the desert killifish under laboratory conditions.

Scale development and its regeneration potency were evaluated in a desert killifish Aphaniops hormuzensis (family Aphaniidae) in laboratory conditions by using light and scanning electron microscopy. Scale development in A. hormuzensis took 156 days at room temperature. Four specific regions of scale formation were detected. The first scale development began 13 days post-hatching (dph) (total length [TL] = 8.5 mm) at the caudal peduncle region and is extended anteriorly 26 dph (TL = 13.6 mm) at the area below the dorsal fin. Scales began forming independently in the head region at 33 dph (TL = 21.7 mm), and in the abdominal region, began at 41 dph (TL = 25.8 mm). Additional points of scale origin were detected on the sides of the operculum or behind and below the eyes. Scale regeneration in the caudal peduncle started 6 days after removal (dar). In 16 dar, the microstructural features appeared and the growth circles, a wide and oblong focus (focus length = 0.6 ± 0.05 µm), and lepidonts were also formed. In 36 dar, the scale shape was gradually changed from circular to a polygon, and radii were distinguishable in the anterior field. The pattern of scale formation could be useful in enhancing the understanding of systematics and phylogeny, functional morphology, and habitat use. It could also be useful in helping to define the Larval/juvenile transition period.

Alpha-Synuclein Clearance through Inhibiting Akt/mTOR Pathway by Microfluidic Encapsulated Induced Conjunctival MSCs in a Parkinsonian Model.

Background & Objective: Parkinson's disease (PD) is a progressive neurodegenerative disorder in which the cause is attributed to the alpha-synuclein (α-Syn) accumulation due to the decreased rate of autophagy. Due to the many advantages, mesenchymal stem cells (MSCs), such as the secretion of neurotrophic factors, have been proposed for PD cell therapy. The present study, in continuation of the previous study, aimed to investigate the therapeutic effect of human-derived Conjunctival MSCs (CJ-MSCs) on the clearance of α-Syn by the microRNA-149(miR-149)/Akt/mTOR/ pathway. Methods: Stereotaxic 6-hydroxy dopamine (6-OHDA) was injected directly into the medial forebrain bundle (MFB) to induce Parkinson's disease. An apomorphine-induced rotation test was used to confirm the model establishment. CJ-MSCs were encapsulated in alginate microgel using a microfluidic system. The green fluorescent protein (GFP) labeled CJ-MSCs were encapsulated, and free cells were transplanted into the rats' right striatum. Behavioral and molecular analyses evaluated the potency of CJ-MSCs (encapsulated and free cells) in PD rats. Real-Time Quantitative Reverse Transcription PCR (qRT-PCR) was performed to investigate the expression of the miR-149-5p, Akt, mTOR, and α-Syn. Results: Our obtained results indicated that transplantation of CJ-MSCs leads to a decrease in the number of rotations while raising the balance and motor abilities. The gene expression evaluation showed a significant reduction in Akt, mTOR, and α-Syn mRNA levels and a significant increase in the level of miR-149-5p compared to the control group. Conclusion: It seems that CJ-MSCs can promote the degradation of intracellular α-Syn by miR-149-5p/Akt/mTOR pathway and improve rats' motor functions.

Habitat and river riparian assessment in the Hyrcanian Forest Ecoregion in Iran: providing basic information for the river management and rehabilitation.

The Hyrcanian Forest holds broad leaf forest remnants dating back to the early Cenozoic Era, which once covered a vast area of the North Temperate Zone. Today, many rivers within this region have been altered by human activities and urgently need rehabilitation. In this regard, 35 wadeable rivers including 14 reference and impacted sites were investigated to determine how different human pressures altered riverine landscapes and habitats. Hence, five common human pressures (agriculture, urbanization, aquaculture, dams, aggregate mining) were identified, then the riverine landscape and habitat condition of each site were assessed. At each site, 17 aquatic, riparian, and terrestrial features, including abiotic and biotic substrate types, were investigated. The number and ratio of pressure-influenced channel features and substrate types differed from those in reference sites. Reference sites were dominated by microlithal, mesolithal, and macrolithal abiotic substrates and large wood, algae, and coarse particulate organic matter biotic substrates. Urbanized sites were most altered and dominated by single channels, steep unvegetated riprap banks, and algae substrate. The results provide valuable information for managers and decision-makers to restore riverine ecosystems considering the impaired parameters resulting from human pressures.

Upregulation of MiRNA-149-5p Reduces the Infract Volume in Middle Cerebral Artery Occlusion Rats by Modulating Cation-Chloride Cotransporters Expressions

Background: Brain ischemia often leads to the chloride gradient alternations, which affects volume regulation and neuronal survival. Increase in NKCC1 expression and reduction in KCC2 level under ischemic condition results in inflammation and neuronal death. In this study, we investigated the effect of mimic miRNA and coenzyme Q10 (CoQ10) on the expression of cation-chloride cotransporters (CCCs) (NKCC1 and KCC2) after cerebral ischemia. Methods: In this study, cerebral ischemia was modeled using the middle cerebral artery occlusion method. Rats were randomly divided into six groups: sham, model, negative control, vehicle, and the first and second treatments. In the Sham group, ischemia was not induced, and no treatment was performed. In the Model group, ischemia induction was performed, and other groups, in addition to ischemia induction, received Scramble miRNA, Ethanol, mimic miRNA-149-5p and CoQ10, respectively. Each group was divided into three subgroups to assess the volume of the tissue damage and neurological deficits scores (NDS) in subgroup 1, brain water content in subgroup 2, level of miRNA-149-5p and CCC expressions in subgroup 3. Results: Our data suggested that the use of mimic miRNA and Q10 increased the level of miRNA-149 and KCC2 expression and decreased NDS, NKCC1 expression, brain water content, and infract volume. Conclusion: Findings of this study suggest that the mimic miRNA and Q10 may have neuroprotective effects through reducing infract volume and brain water content and modulating the expression of CCCs after brain ischemia.

Prevention of peritoneal adhesions formation by core-shell electrospun ibuprofen-loaded PEG/silk fibrous membrane.

Adhesion bands are pathological fibrous tissues that create in the middle of tissues and organs, often reasons of intestinal obstruction, and female infertility. Here, we explored the anti-adhesive and inflammatory capacities of PEG/silk and Ibuprofen-loaded PEG/Silk core-shell nanofibrous membranes, respectively. The ibuprofen-loaded Silk Fibroin-Poly ethylene Glycol (SF-PEG) core-shell membrane was fabricated by electrospinning and considered in terms of morphology, surface wettability, drug release, and degradation. To reveal the membrane capability for adhesion bands inhibition, the membrane was stitched among the abdominal partition and peritoneum and then evaluated using two scoring adhesion systems. According to results, the fibrous membrane hindered cell proliferation, and the scoring systems and pathology showed that in a rat model, Ibuprofen-loaded PEG/Silk core-shell membrane caused a lightening in post-operative adhesion bands and the low-grade inflammatory reaction in animal models. Collectively, we fabricated new ibuprofen-loaded PEG/SF membranes with anti-adhesion and anti-inflammation properties. Moreover, this core-shell electrospun fibrous membrane has not even now been used to prevent peritendinous adhesion generation.

The influence of climate change on the suitable habitats of Allium species endemic to Iran.

Identifying the consequences of global warming on the potential distribution of plant taxa with high species diversity or a high proportion of endemic species is one of the critical steps in conservation biology. Here, present and future spatial distribution patterns of 20 Allium endemic species were predicted in Iran. In this regard, the maximum entropy model (MaxEnt) and seven environmental factors were applied. In addition, optimistic (RCP2.6) and pessimistic (RCP8.5) scenarios of 2050 and 2080 were also considered to predict the future spatial distributions. The results showed that annual mean temperature (BIO1), temperature annual range (P5-P6) (BIO7), soil organic carbon content, annual precipitation (BIO12), and depth of soil were the most important environmental variables affecting the distributions of the studied taxa. In total, the model predictions under the future scenarios represented that the suitable habitats for all Allium species endemic to Zagros except for A. saralicum and A. esfahanicum are most probably increased. In contrast, the suitable habitats for all species in Azerbaijan Plateau, Kopet Dagh-Khorassan region, and Alborz except for A. derderianum are most likely decreased under the future climate conditions. The present study indicates that the habitats of Alborz, Azarbaijan, and Kopet Dagh-Khorassan will be probably very fragile and vulnerable to climate change and most species will respond strongly negatively under applied scenarios, while Zagros species occupy new habitats by expanding their distributions. Therefore, determining conservation strategies for the species in these regions seems to be very important and high priority for decision makers.

Increased Expression of Tight Junction Proteins and Blood-Brain Barrier Integrity in MCAO Rats Following Injection of miR-149-5p.

Cerebral ischemia is a common neurodegenerative disease in which damage to the blood-brain barrier (BBB) is the main consequence. In cerebral ischemia, the level of miR-149-5p and tight junction proteins are decreased, while the level of Calpine is increased, finally leading to increased BBB permeability. This study investigated the effect of miR-149-5p mimic on the expression of Calpain, Occludin, and ZO-1 and the consequences of cerebral ischemia. Cerebral ischemia model was performed via middle cerebral artery occlusion (MCAO) method on female Wistar rats. Four groups of Wistar rats were studied: Sham, cerebral ischemia without treatment, Scramble miR, and miR-149-5p mimic treatment. Then, neurological defects and BBB permeability (via Evans blue staining), cerebral edema (cerebrospinal fluid percentage), and ZO-1, Occludin, and Calapin expression (by quantitative real time- PCR) were investigated. qRT-PCR results showed miR-149-5p expression decreases after cerebral ischemia induction. In addition, Occludin and ZO-1 expression significantly increased in miR-149-5p group. In contrast, Calapin expression, BBB permeability, brain water content and neurological defects were significantly decreased. It seems that the increased level of miR-149-5p exerts its protective effect on cerebral ischemia due to increasing of tight junction proteins.

Modeling climate change effects on spatial distribution of wild Aegilops L. (Poaceae) toward food security management and biodiversity conservation in Iran.

The demand for food resources is increasing quickly because human populations are growing; therefore, food security may become one of the largest human challenges of this century. Crop wild relatives (CWRs) are the most valuable plant genetic resources (PGR) for the conservation of genetic diversity in crops. However, climate change is an added pressure on biodiversity, particularly on this valuable group of plants. It is predicted that more than 50% of this group may be lost by 2055 as a result of the effects of climate change. Iran ranks high in the world in its conservation priorities for CWRs. This study investigates the impacts of climate change on Aegilops L. as important CWRs. MaxEnt was applied to predict the spatial distribution of seven Aegilops species under different climatic scenarios (RCP 2.6 and RCP 8.5) of 2050 and 2080. According to the findings, all species exhibited reduction or expansion responses under all of the above-mentioned climatic scenarios. However, the range change was negative for some species (i.e., Aegilops columnaris, Aegilops cylindrica, Aegilops speltoides, Aegilops tauschii [in all scenarios of 2050 and 2080], and Aegilops kotschyi [RCP 2.6 2050 and 2080]), and positive for others (i.e., Aegilops crassa, Aegilops triuncialis [in all scenarios of 2050 and 2080], and Aegilops kotschyi [RCP 8.5 2050 and 2080]). The results of this study emphasize the need for conservation plans for the country's genetic resources, including regular monitoring and assessment of ecological and demographic changes. Integr Environ Assess Manag 2022;18:697-708. © 2021 SETAC.

Using Bilateral tDCS to Modulate EEG Amplitude and Coherence of Men With Opioid Use Disorder Under Methadone Therapy: A Sham-controlled Clinical Trial.

Objective. This study aimed to investigate the effect of bilateral transcranial direct current stimulation (tDCS) on the electroencephalography (EEG) amplitude and coherence in male patients with opioid use disorder (OUD), who were under methadone therapy. It compares the effects of active versus sham tDCS. Methods. This is a double-blind sham-controlled clinical trial. Participants were 30 male patients with OUD; they were divided into 3 groups of left anode/right cathode tDCS, right anode/left cathode tDCS, and sham tDCS. Their brainwave activity was measured by quantitative EEG before study and then active groups underwent tDCS (2 mA, 20 min) applied over their right/left dorsolateral prefrontal cortex (DLPFC) for 10 consecutive days. After stimulation, they were re-assessed. The collected data were analyzed in SPSS, MATLAB, and NeuroGuide v.2 applications. Results. After active tDCS, a significant decrease in amplitude of slow brain waves (delta, theta, and alpha) in prefrontal, frontal, occipital, and parietal areas, and an increase in the coherence of beta, delta, and theta frequency bands in the parietal, central, and temporal regions of addicts were reported. In the sham group, there was a significant decrease in the amplitude of the alpha wave and in the coherence of delta and theta waves. Conclusion. The active tDCS over the right/left DLPFC, as a noninvasive and complementary treatment, can modulate the amplitude and coherence of brainwaves in patients with OUD.

Therapeutic potentials of human microfluidic encapsulated conjunctival mesenchymal stem cells on the rat model of Parkinson's disease.

BACKGROUND AND AIM: Parkinson's disease (PD) is a progressive neurodegenerative disorder caused by the destruction of the dopaminergic neurons in the nigrostriatal pathway, leading to motor-behavioral complications. Cell therapy has been proposed as a promising approach for PD treatment using various cellular sources. Despite a few disadvantages mesenchymal stem cells (MSCs) represent, they have more auspicious effects for PD cell therapy. The present study aimed to evaluate a new source of MSCs isolated from human Conjunctiva (CJ-MSCs) impact on PD complications for the first time. MATERIALS AND METHODS: Parkinson's was induced by stereotactic injection of 6-hydroxydopamine (6-OHDA) into the right medial forebrain bundle (MFB). An apomorphine-induced rotation test was used to confirm the model establishment. After PD model confirmation, green fluorescent protein (GFP) labeled CJ-MSCs and induced CJ-MSCs (microfluidic encapsulated and non-capsulated) were transplanted into the rats' right striatum. Then Rotation, Rotarod, and Open-field tests were performed to evaluate the behavioral assessment. Additionally, the immunohistochemistry technique was used for identifying tyrosine hydroxylase (TH). RESULTS: According to the obtained data, the cell transplantation caused a reduction in the rats' rotation number and improved locomotion compared to the control group. The previous results were also more pronounced in induced and microfluidic encapsulated cells compared to other cells. Rats recipient CJ-MSCs also have represented more TH-expressed GFP-labeled cell numbers in the striatum than the control group. CONCLUSION: It can be concluded that CJ-MSCs therapy can have protective effects against PD complications and nerve induction of cells due to their ability to express dopamine. On the other hand, CJ-MSCs microencapsulating leads to enhance even more protective effect of CJ-MSCs. However, confirmation of this hypothesis requires further studies and investigation of these cells' possible mechanisms of action.

Using climatic variables alone overestimate climate change impacts on predicting distribution of an endemic species.

Plant species distribution is constrained by both dynamic and static environmental variables. However, relative contribution of dynamic and static variables in determining species distributions is not clear and has far reaching implications for range change dynamics in a changing world. Prunus eburnea (Spach) Aitch. & Hemsl. is an endemic and medicinal plant species of Iran. It has rendered itself as ecologically important for its functions and services and is currently in need of habitat conservation measures requiring investigation of future potential distribution range. We conducted sampling of 500 points that cover most of Iran plateau and recorded the P. eburnea presence and absence during the period 2015-2017. In this study, we evaluated impacts of using only climatic variables versus combined with topographic and edaphic variables on accuracy criteria and predictive ability of current and future habitat suitability of this species under climate change (CCSM4, RCP 2.6 in 2070) by generalized linear model and generalized boosted model. Models' performances were evaluated using area under the curve, sensitivity, specificity and the true skill statistic. Then, we evaluated here, driving environmental variables determining the distribution of P. eburnea by using principal component analysis and partitioning methods. Our results indicated that prediction with high accuracy of the spatial distribution of P. eburnea requires both climate information, as dynamic primary factors, but also detailed information on soil and topography variables, as static factors. The results emphasized that environmental variable grouping influenced the modelling prediction ability strongly and the use of only climate variables would exaggerate the predicted distribution range under climate change. Results supported using both dynamic and static variables improved accuracy of the modeling and provided more realistic prediction of species distribution under influence of climate change.

Neuroprotective effects of coenzyme Q10 in Parkinson's model via a novel Q10/miR-149-5p/MMPs pathway.

Parkinson's disease (PD) is a complex neurodegenerative disease in which the understanding of the underlying molecular mechanisms can be constructive in the diagnosis and treatment. Matrix metalloproteinase (MMPs) elevation and damage to the blood-brain barrier (BBB) are critical mechanisms involved in the PD separation. Studies have revealed that changes in miR-149-5p and CoQ10 are associated with BBB damage, and CoQ10 can affect the levels of some miRs. Hence, in the present study, we aimed to evaluate CoQ10 and miR-149-5p mimic on miR-149-5p, MMPs and TH expression, and behavioral functions of the PD models. PD was induced by injection of 6-OHDA into the rats' Medial Forbrain Bundle (MFB). The behavioral tests, including the Rotation test, Rotarod test, and Open field test, have been directed two weeks after PD induction. Next, the MiR-149-5p mimic (miR-mimic) and CoQ10 have been administered to rats. The same behavioral tests have been evaluated two weeks after administration to investigate the effect of miR-149-5p mimic and CoQ10. The rats were followed extra four weeks, and the behavioral tests have performed again. Finally, the expression of MMPs and miR-149-5p genes was measured using RT-qPCR, and tyrosine hydroxylase (TH) was assessed through immunohistochemistry analysis. According to the obtained results, the level of miR-149-5p has decreased, followed by PD induction in rats. RT-qPCR analysis has represented upregulation and downregulation of miR-149-5p and MMP-2,9, respectively, after miR-mimic and CoQ10 treatment. The treated rats have also represented improved motor function and increased TH + cells in the striatum according to the behavioral tests and immunohistochemistry assay. Taking together miR-149 and CoQ10 has shown to have an impressive potential to prevent damage to dopaminergic neurons caused by 6-OHDA injection through reducing MMP-2,9, increased TH expression, and improved motor function.

A sham-controlled clinical trial to examine the effect of bilateral tDCS on craving, TNF-α and IL-6 expression levels, and impulsivity of males with opioid use disorder.

BACKGROUND: Opioid use disorder (OUD) is one of the problems and concerns of all countries in the world. On the other hand, transcranial direct current stimulation (tDCS) has been used as a new therapeutic intervention in various psychiatric disorders. OBJECTIVE: This study aimed to investigate the effect of bilateral tDCS on the expression levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), craving and impulsive behaviors of male patients with OUD. METHODS: This is a double-blind sham-controlled clinical trial. Participants were 31 male patients with OUD divided into three groups of left anode/right cathode tDCS, right anode/left cathode tDCS, and sham tDCS. They received active tDCS (2 mA, 20 min), applied over their dorsolateral prefrontal cortex (DLPFC) for 10 consecutive days. Expression levels of IL-6 and TNF-α cytokines were measured using ELISA method, and the Desires for Drug Questionnaire and the Barratt Impulsiveness Scale version 11 were used to assess the craving and impulsivity of subjects, respectively. RESULTS: Both active and sham tDCS could significantly reduce drug craving in subjects (p < 0.05). Active tDCS over the right/left DLPFC significantly reduced impulsivity and its dimensions (overall, attentional, motor, and nonplanning) compared to the sham tDCS (p < 0.05). It could also reduce the expression levels of IL-6 and TNF-α, but the difference was not statistically significant. CONCLUSIONS: The active tDCS over the right/left DLPFC, as a noninvasive and complementary treatment, can be used along with other common methods for the treatment of patients with OUD. It can improve their cognitive functions by reducing impulsivity.

The neuroprotective effect of MicroRNA-149-5p and coenzymeQ10 by reducing levels of inflammatory cytokines and metalloproteinases following focal brain ischemia in rats.

The increase in some factors following cerebral ischemia, especially Matrix metalloproteinase (MMPs) and inflammatory factors lead to blood-brain barrier (BBB) damages, edema and neuronal death. Previous studies have shown that these molecules are miRNA-149-5p (miR-149) and Coenzyme (Co) Q10 targets. Therefore, in this study, the effect of mimic of miRNA-149-5p (mimic miR) and CoQ10 on the expression of metalloproteinase 1 and 2 and inflammatory cytokines following injury caused by cerebral ischemia is investigated. Cerebral ischemia was modeled by Middle Cerebral Artery Occlusion (MCAO). Male Wistar rats were randomly divided into 6 groups: sham (without surgery and treatment), control (MCAO), negative control (NC): MCAO + scrambled miR, vehicle: MCAO + Ethanole, first treatment: MCAO + mimic miR, second treatment: MCAO + Q10. Each group was divided into 6 subgroups to evaluate neurological defects, the volume of tissue damage using 2,3,5-triphenyl tetrazolium chloride (TTC) staining, blood-brain barrier permeability using cerebral Evans Blue (EB) staining, edema by measuring the percentage of brain water, MMP-2,9 mRNA and miR-149-5p levels using Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) and the levels of IL-6 and TNF-α proteins using ELISA. The data obtained from this study showed that the use of mimic miR and Q10 increased the level of miR-149, decreased the extent of neurological defects and tissue damage, increased BBB integrity, decreased brain water percentage and also decreased the level of inflammatory cytokines and MMPs. It seems that the use mimic of miRNA-149-5p and Q10 can have a protective effect on the brain by reducing MMPs and inflammatory factors following cerebral ischemia and this could lead to a new treatment strategy to reduce the complications of cerebral ischemia.