Effects of novel beta-lactam, MC-100093, and ceftriaxone on astrocytic glutamate transporters and neuroinflammatory factors in nucleus accumbens of C57BL/6 mice exposed to escalated doses of morphine.

Chronic exposure to opioids can lead to downregulation of astrocytic glutamate transporter 1 (GLT-1), which regulates the majority of glutamate uptake. Studies from our lab revealed that beta-lactam antibiotic, ceftriaxone, attenuated hydrocodone-induced downregulation of GLT-1 as well as cystine/glutamate antiporter (xCT) expression in central reward brain regions. In this study, we investigated the effects of escalating doses of morphine and tested the efficacy of novel synthetic non-antibiotic drug, MC-100093, and ceftriaxone in attenuating the effects of morphine exposure in the expression of GLT-1, xCT, and neuroinflammatory factors (IL-6 and TGF-ß) in the nucleus accumbens (NAc). This study also investigated the effects of morphine and beta-lactams in locomotor activity, spontaneous alternation percentage (SAP) and number of entries in Y maze since opioids have effects in locomotor sensitization. Mice were exposed to moderate dose of morphine (20 mg/kg, i.p.) on days 1, 3, 5, 7, and a higher dose of morphine (150 mg/kg, i.p.) on day 9, and these mice were then behaviorally tested and euthanized on Day 10. Western blot analysis showed that exposure to morphine downregulated GLT-1 and xCT expression in the NAc, and both MC-100093 and ceftriaxone attenuated these effects. In addition, morphine exposure increased IL-6 mRNA and TGF-ß mRNA expression, and MC-100093 and ceftriaxone attenuated only the effect on IL-6 mRNA expression in the NAc. Furthermore, morphine exposure induced an increase in distance travelled, and MC-100093 and ceftriaxone attenuated this effect. In addition, morphine exposure decreased the SAP and increased the number of arm entries in Y maze, however, neither MC-100093 nor ceftriaxone showed any attenuating effect. Our findings demonstrated for the first time that MC-100093 and ceftriaxone attenuated morphine-induced downregulation of GLT-1 and xCT expression, and morphine-induced increase in neuroinflammatory factor, IL-6, as well as hyperactivity. These findings revealed the beneficial therapeutic effects of MC-100093 and ceftriaxone against the effects of exposure to escalated doses of morphine.

Role of diosmin in preventing doxorubicin-induced cardiac oxidative stress, inflammation, and hypertrophy: A mechanistic approach.

Chemotherapeutic drugs, such as doxorubicin (Dox), are commonly used to treat a variety of malignancies. However, Dox-induced cardiotoxicity limits the drug's clinical applications. Hence, this study intended to investigate whether diosmin could prevent or limit Dox-induced cardiotoxicity in an animal setting. Thirty-two rats were separated into four distinct groups of controls, those treated with Dox (20 mg/kg, intraperitoneal, i.p.), those treated with diosmin 100 mg plus Dox, and those treated with diosmin 200 mg plus Dox. At the end of the experiment, rats were anesthetized and sacrificed and their blood and hearts were collected. Cardiac toxicity markers were analyzed in the blood, and the heart tissue was analyzed by the biochemical assays MDA, GSH, and CAT, western blot analysis (NF-kB, IL-6, TLR-4, TNF-α, iNOS, and COX-2), and gene expression analysis (ß-MHC, BNP). Formalin-fixed tissue was used for histopathological studies. We demonstrated that a Dox insult resulted in increased oxidative stress, inflammation, and hypertrophy as shown by increased MDA levels and reduced GSH content and CAT activity. Furthermore, Dox treatment induced cardiac hypertrophy and damage, as evidenced by the biochemical analysis, ELISA, western blot analysis, and gene expression analysis. However, co-administration of diosmin at both doses, 100 mg and 200 mg, mitigated these alterations. Data derived from the current research revealed that the cardioprotective effect of diosmin was likely due to its ability to mitigate oxidative stress and inflammation. However, further study is required to investigate the protective effects of diosmin against Dox-induced cardiotoxicity.

Significant differences in the length and weight measurements of Jordanian infants compared to the World Health Organization 2006 growth standards.

BACKGROUND: In 2006, the World Health Organization (WHO) introduced new growth standards based on data derived globally from optimally nourished breastfed infants. The aim of this study was to assess the effects of implementing WHO growth standards on the growth patterns of Jordanian infants. In addition, it was to ascertain the necessity of establishing country-specific growth standards and charts tailored to Jordanian infants. MATERIALS AND METHODS: The data of 102,846 infants (50.1% boys, 49.9% girls) aged 0-24 months, from 115 primary healthcare centers across the country were retrieved from a National E-health Program. Weight and length measurements were analyzed, and age- and sex-specific z-scores were calculated relative to the WHO growth standards. Data was analyzed using SPSS version 26. Mann-Whitney U test was performed to determine significant differences between the measurements for boys and girls in terms of age, length, and weight. RESULTS: Jordanian infants exhibited significantly shorter length-for-age measurements than WHO standards with mean z-scores of -0.56 and -0.38, for boys and girls, respectively. Weight-for-age measurements showed a good fit and were comparable to the WHO growth standards for boys (mean z score = -0.05) and girls (mean z score = 0.04). Notably, Jordanian infants displayed higher weight-for-length measurements, with mean z-scores of 0.51 for boys and 0.47 for girls. CONCLUSION: The availability of Jordanian-specific growth standards will improve the accuracy of assessing infant growth and enhance the monitoring and evaluation of their health and development.

Statistical design and optimization of nano-transfersomes based chitosan gel for transdermal delivery of cefepime.

OBJECTIVES: This research aimed to overcome challenges posed by cefepime excessive elimination rate and poor patient compliance by developing transdermal delivery system using nano-transfersomes based chitosan gel. METHODS: Rotary evaporation-sonication method and the Box-Behnken model were used to prepare cefepime loaded nano-transfersomes (CPE-NTFs). The physiochemical characterization of CPE-NTFs were analyzed including DLS, deformability index, DSC and antimicrobial study. Optimized CPE-NTFs loaded into chitosan gel and appropriately characterized. In vitro release, ex vivo and in vivo studies were performed. RESULTS: The CPE-NTFs were physically stable with particle size 222.6 ± 1.8 nm, polydispersity index 0.163 ± 0.02, zeta potential -20.8 ± 0.1 mv, entrapment efficiency 81.4 ± 1.1% and deformability index 71 ± 0.2. DSC analysis confirmed successful drug loading and thermal stability. FTIR analysis showed no chemical interaction among the excipients of CPE-NTFs gel. The antibacterial activity demonstrated a remarkable reduction in the minimum inhibitory concentration of cefepime when incorporated into nano-transfersomes. CPE-NTFs based chitosan gel (CPE-NTFs gel) showed significant physicochemical properties. In vitro release studies exhibited sustained release behavior over 24 h, and ex vivo studies indicated enhanced permeation and retention compared to conventional cefepime gel. In vivo skin irritation studies confirmed CPE-NTFs gel was nonirritating and biocompatible for transdermal delivery. CONCLUSION: This research showed nano-transfersomes based chitosan gel is a promising approach for cefepime transdermal delivery and provides sustained release of cefepime.

Design, synthesis, molecular docking study, and α-glucosidase inhibitory evaluation of novel hydrazide-hydrazone derivatives of 3,4-dihydroxyphenylacetic acid.

A series of novel Schiff base derivatives (1-28) of 3,4-dihydroxyphenylacetic acid were synthesized in a multi-step reaction. All the synthesized Schiff bases were obtained in high yields and their structures were determined by 1HNMR, 13CNMR, and HR-ESI-MS spectroscopy. Except for compounds 22, 26, 27, and 28, all derivatives show excellent to moderate α-glucosidase inhibition. Compounds 5 (IC50 = 12.84 ± 0.52 µM), 4 (IC50 = 13.64 ± 0.58 µM), 12 (IC50 = 15.73 ± 0.71 µM), 13 (IC50 = 16.62 ± 0.47 µM), 15 (IC50 = 17.40 ± 0.74 µM), 3 (IC50 = 18.45 ± 1.21 µM), 7 (IC50 = 19.68 ± 0.82 µM), and 2 (IC50 = 20.35 ± 1.27 µM) shows outstanding inhibition as compared to standard acarbose (IC50 = 873.34 ± 1.67 µM). Furthermore, a docking study was performed to find out the interaction between the enzyme and the most active compounds. With this research work, 3,4-dihydroxyphenylacetic acid Schiff base derivatives have been introduced as a potential class of α-glucosidase inhibitors that have remained elusive till now.

Association between COVID-19 severity and tobacco smoking status: a retrospective cohort study using propensity score matching weights analysis.

INTRODUCTION: The COVID-19 pandemic continues to be a global threat to public health, with over 766 million confirmed cases and more than 6 million reported deaths. Patients with a smoking history are at a greater risk of severe respiratory complications and death due to COVID-19. This study investigated the association between smoking history and adverse clinical outcomes among COVID-19 patients admitted to a designated medical centre in Saudi Arabia. METHODS: A retrospective observational cohort study was conducted using patient chart review data from a large tertiary medical centre in the eastern region of the country. Patients admitted between January and December 2020 were screened. The inclusion criteria were ≥18 years of age and confirmed COVID-19 infection via reverse-transcription-PCR. The exclusion criteria were unconfirmed COVID-19 infection, non-COVID-19 admissions, unconfirmed smoking status, vaccinated individuals, essential chart information missing or refusal to consent. Statistical analyses comprised crude estimates, matching weights (as the main analysis) and directed acyclic graphs (DAGs) causal pathway analysis using an ordinal regression model. RESULTS: The sample comprised 447 patients (never-smoker=321; ever-smoker=126). The median age (IQR) was 50 years (39-58), and 73.4% of the sample were males. A matching weights procedure was employed to ensure covariate balance. The analysis revealed that the odds of developing severe COVID-19 were higher in the ever-smoker group with an OR of 1.44 (95% CI 0.90 to 2.32, p=0.130). This was primarily due to an increase in non-invasive oxygen therapy with an OR of 1.05 (95% CI 0.99 to 1.10, p=0.101). The findings were consistent across the different analytical methods employed, including crude estimates and DAGs causal pathway analysis. CONCLUSION: Our findings suggest that smoking may increase the risk of adverse COVID-19 outcomes. However, the study was limited by its retrospective design and small sample size. Further research is therefore needed to confirm the findings.

The Efficacy of Hispidin and Magnesium Nanoparticles against Zearalenone-Induced Fungal Toxicity Causing Polycystic Ovarian Syndrome in Rats.

Contamination by fungi and the toxins they secrete is a worldwide health concern. One such toxin is zearalenone (Zea), which is structurally similar to the hormone estrogen, interferes with its action on the reproductive system, and is therefore classified as an endocrine disruptor. This study aims to determine the effectiveness of hispidin and magnesium nanoparticles (MgONPs) against zearalenone-induced myotoxicity, which causes polycystic ovary syndrome (PCOS) in rats. A three-month exposure study was performed using female Wistar rats (n = 42) with an average weight of 100-150 g. The animals were divided into six groups (I to VI) of seven rats each. Group I was administered distilled water as a negative control. Group II was exposed to Zea 0.1 mg/kg b.w. through gavage daily. Group III was treated with 0.1 mg/kg of hispidin through gavage daily. Group IV was given 150 µg/mL MgONPs orally each day. Group V was treated with Zea 0.1 mg/kg b.w. + 0.1 mg/kg hispidin orally each day. Group VI was treated with Zea 0.1 mg/kg b.w. and the combination treatment of 0.1 mg/kg hispidin + 150 µg/mL MgONPs through gavage every day. The effectiveness of hispidin and MgONPs against Zea toxicity was evaluated in terms of ovarian histological changes, gene expression, oxidative stress biomarkers, biochemical variables, and hormone levels. The findings showed that exposure to Zea promotes PCOS in rats, with Zea-treated rats displaying hyper-ovulation with large cysts; elevated testosterone, luteinizing hormone, insulin, and glucose; and reduced sex hormone-binding globulin. In addition, qRT-PCR for aromatase (Cyp19α1) showed it to be downregulated. Treatment with hispidin improved the histopathological and hormonal situation and rescued expression of Cyp19α. Our data indicate the potential therapeutic effects of hispidin against Zea-induced Fungal Toxicity.

An Online-Based Survey to Assess Knowledge, Attitudes, and Barriers to Perform First Aid after Road Accidents Conducted among Adult Jordanians.

(1) Background: First aid administered during road accidents can save millions of lives. However, the knowledge and attitudes of the Jordanian population towards first aid are lacking. This study aimed to examine the knowledge, attitudes, and barriers to performing first aid among the Jordanian population during road accidents. (2) Methods: An online questionnaire was developed and distributed using various Jordanian social media platforms. The questionnaire collected the participants' sociodemographic details and assessed their first aid knowledge, attitudes toward first aid, and barriers preventing the participants from performing first aid in emergencies. (3) Results: 732 participants participated in this study. The median knowledge score regarding first aid items was 9 (7-10) out of the maximum possible score of 15. The median first aid attitude score was 24 (22-27) out of a maximum possible score of 30. The most commonly reported barrier to performing first aid among the participants was "lack of first aid training" (76.78%), followed by "lack of knowledge about first aid" (75.81%) and "fear of performing first aid" (57.51%). The participants with lower income levels exhibited more negative attitudes towards first aid (4). Conclusions: This study underscores the urgent need for enhanced first aid training and awareness in Jordan. The participants' first-aid knowledge overall was limited, although positive attitudes toward first-aid delivery were observed. The findings emphasize the need for regular and structured first-aid training courses, addressing barriers such as fear and misinformation and ensuring accessibility across all socioeconomic levels to improve preparedness for road traffic accidents and other emergencies. This comprehensive approach can better equip the Jordanian population to effectively manage emergencies and improve public health outcomes.

Development and Validation of the Jordanian Diabetic Health Literacy Questionnaire: Enhancing Diabetes Management in Arabic-Speaking Populations.

(1) Background: Amidst the global rise in type 2 diabetes mellitus (T2DM), effective management of the disease has become increasingly important. Health literacy, particularly in non-English speaking populations, plays a crucial role in this management. To address the lack of suitable tools for Arabic-speaking diabetic patients, this study developed and validated the Jordanian Diabetic Health Literacy Questionnaire (JDHLQ). (2) Methods: A sample of 400 diabetic patients from Jordan, with a balance in gender, age, and educational background, was recruited from an endocrinology outpatient clinic. The JDHLQ, consisting of informative and communicative sections, underwent rigorous validation. Utilizing principal component analysis and Rasch analysis, the JDHL's reliability and validity were evaluated. (3) Results: The results showed moderate proficiency in understanding and communicating diabetes-related information and confirmed the reliability and validity of the JDHLQ. (4) Conclusions: These findings emphasize the importance of culturally appropriate health literacy tools in enhancing patient understanding, engagement, and overall management of T2DM in Arabic-speaking communities.

Acceptance of Flu Vaccine among Parents of Diabetic Children in Jordan.

There is a critical need to understand vaccine decision-making in high-risk groups. This study explored flu vaccine acceptance among Jordanian parents of diabetic children. Employing a cross-sectional approach, 405 parents from multiple healthcare centers across Jordan were recruited through stratified sampling, ensuring a broad representation of socioeconomic backgrounds. A structured questionnaire, distributed both in-person and online, evaluated their knowledge, attitudes, and acceptance of the flu vaccine for their diabetic children. The results indicated that only 6.4% of the study sample reported vaccinating their children against the flu annually, and only 23% are planning to vaccinate their children this year. A multinomial logistic regression analysis revealed notable variability in responses. Specifically, parents with a positive attitude towards the flu vaccine and those with older children had less odds to reject the vaccine (OR = 0.589, 95% CI (0.518-0.670), p < 0.001 and OR = 0.846, 95% CI (0.736-0.974), p = 0.02, respectively). Conversely, prevalent misconceptions regarding vaccine safety and efficacy emerged as significant barriers to acceptance. Our findings advocate for targeted educational programs that directly address and debunk these specific misconceptions. Additionally, strengthened healthcare communication to provide clear, consistent information about the flu vaccine's safety and benefits is vital to help enhance vaccine uptake among this vulnerable population, emphasizing the need to address specific concerns and misinformation directly.

Triglyceride Glucose Index as an Indicator of Cardiovascular Risk in Syrian Refugees.

Background: The triglyceride glucose (TyG) index is a quick and inexpensive approach to measure insulin resistance. The aim of this study was to evaluate the TyG index's ability to predict cardiovascular risk and determine the TyG index cutoff values in Syrian refugees. Methods: A retrospective research study was conducted with 756 Syrian refugees. Data on demographics and clinical laboratory assessments were obtained from refugee's files. The formula Ln [fasting triglycerides (mg/dL) × fasting plasma glucose (mg (dL)/2] was used to calculate the TyG index. The Framingham risk score was used to calculate ten-year cardiovascular risk. The TyG index cutoff point was determined using the receiver operating characteristic curve (ROC). Results: Included participants had a mean age of 56.76 ± 10.78 years and a mean body mass index (BMI) of 27.42 ± 4.03 kg/m2. 28.57% of the subjects were smokers, and the majority were female (56.75%). A significant moderate correlation was observed between TyG index and Framingham score (r = 0.428, p < 0.001). ROC curve analysis for TyG index and Framingham score showed an area under the curve (AUC) of 0.741 (95% CI = 0.691-0.791; p < 0.001). The cutoff value of the TyG index to recognize intermediate/high risk Framingham risk score was 9.33, with a sensitivity of 64.3%, and specificity of 75.0%. Conclusion: Our findings determine that, given a TyG index cutoff value of 9.33, the TyG index has a predictive ability to assess ten-year cardiovascular risk by comparison to the Framingham risk score in a high-risk group of Syrian refugees and can be used as an independent indicator of cardiovascular risk.

Methanol intoxication in the central region of Saudi Arabia: Five case studies.

Outbreaks of methanol poisoning have been described in the medical literature worldwide. However, the few outbreaks that have occurred in Saudi Arabia remain undocumented. This is especially noteworthy in light of the fact that Saudi Arabia is among the countries that explicitly prohibit the usage of alcoholic beverages and recreational drugs. Herein, we describe five cases of methanol poisoning in Saudi Arabia. The first three comprise patients admitted to the emergency room (ER) with signs of methanol toxicity, such as heart palpitations, vomiting, and blurred vision; otherwise, those patients were considered medically free. The remaining two cases were examined postmortem. A headspace gas chromatography-flame ionization detector was used to test blood, vitreous humor, and urine samples for methanol. Specific lethal concentrations of methanol were defined based on published case studies as 23-740 mg/dL in blood and 12-396 mg/dL in vitreous humor. In postmortem cases of our present study, samples exhibited lethal concentrations: 118 and 257 mg/dL in blood, 116.3 and 283 mg/dL in vitreous humor. In ER cases, methanol concentrations in urine samples were lower, at 7.5, 9.1, and 20.9 mg/dL; however, toxic symptoms were still observed. These case studies indicate that it is necessary to raise community awareness about the risk of methanol poisoning in order to minimize future poisoning epidemics.

Synthesis, molecular docking and DFT analysis of novel bis-Schiff base derivatives with thiobarbituric acid for α-glucosidase inhibition assessment.

A library of novel bis-Schiff base derivatives based on thiobarbituric acid has been effectively synthesized by multi-step reactions as part of our ongoing pursuit of novel anti-diabetic agents. All these derivatives were subjected to in vitro α-glucosidase inhibitory potential testing after structural confirmation by modern spectroscopic techniques. Among them, compound 8 (IC50 = 0.10 ± 0.05 µM), and 9 (IC50 = 0.13 ± 0.03 µM) exhibited promising inhibitory activity better than the standard drug acarbose (IC50 = 0.27 ± 0.04 µM). Similarly, derivatives (5, 6, 7, 10 and 4) showed significant to good inhibitory activity in the range of IC50 values from 0.32 ± 0.03 to 0.52 ± 0.02 µM. These derivatives were docked with the target protein to elucidate their binding affinities and key interactions, providing additional insights into their inhibitory mechanisms. The chemical nature of these compounds were reveal by performing the density functional theory (DFT) calculation using hybrid B3LYP functional with 6-311++G(d,p) basis set. The presence of intramolecular H-bonding was explored by DFT-d3 and reduced density gradient (RGD) analysis. Furthermore, various reactivity parameters were explored by performing TD-DFT at CAM-B3LYP/6-311++G(d,p) method.

The effect of inhibiting hindbrain A2 noradrenergic neurons by 6-Hydroxydopamine on lipopolysaccharide-treated male rats autistic animal model.

Autism spectrum disorder (ASD) is a complex neurodevelopmental illness that often emerges in early childhood. The incidence of ASD has shown a notable rise in recent years. ASD is defined by deficits in social communication, and presence of rigid and repetitive behaviors and interests. The underlying mechanisms of ASD remain elusive. Multiple studies have documented the presence of neuroinflammation and increased levels of inflammatory cytokines, specifically, IL-6, TNF, and NF-κB, in various brain regions, including the prefrontal cortex (PFC) and hippocampus in individuals with ASD. Noradrenergic neurons play a crucial role in brain development and the regulation of motor, behavioral, and memory functions. This study sought to examine the impact of intracerebroventricular (icv.) injection of the neurotoxin, 6-hydroxydopamine (6-OHDA), in the caudal dorsal vagal complex A2 neurons on various neuroinflammatory pathways at the hippocampus and PFC in valproic acid (VPA) autistic animal model. This was done in conjunction with an intraperitoneal (i.p.) injection of Lipopolysaccharides (LPS) in animal models with VPA-induced autism. We specifically examined the impact of the caudal fourth ventricle 6-OHDA icv. injection and LPS (i.p.) injection on self-grooming behavior. We measured the mRNA expression of IL-6, TNF-a, and NF-κB using qRT-PCR, and the protein expression of COX-2, GPX-1, p-AMPK, and AMPK using western blot analysis. The self-grooming activity was considerably higher in the combined treatment group (6-OHDA icv. + LPS i.p.) compared to the control group. A substantial increase observed in the expression of IL-6, TNF-α, and NF-κB genes in the PFC of the treatment group that received icv. Administration of 6-OHDA, compared to the control group. The VPA-autism rats that received the combo treatment exhibited a slight increase in the expression level of NF-κB gene in the hippocampus, compared to the control group. At the PFC, we noticed a substantial drop in the expression of the antioxidant protein GPX-1 in the group that received the combo treatment compared to the control group. Our data investigates a novel aspect that the 6-OHDA-induced inhibition of hindbrain A2 neurons could be influencing the neuroinflammatory pathways in the PFC and hippocampus of autistic animal models.

Synthesis, characterization, Hirshfeld surface analysis, antioxidant and selective ß-glucuronidase inhibitory studies of transition metal complexes of hydrazide based Schiff base ligand.

The synthesis of N'-[(4-hydroxy-3-methoxyphenyl)methylidene] 2-aminobenzohydrazide (H-AHMB) was performed by condensing O-vanillin with 2-aminobenzohydrazide and was characterized by FTIR, high resolution ESI(+) mass spectral analysis, 1H and 13C-NMR. The compound H-AHMB was crystallized in orthorhombic Pbca space group and studied for single crystal diffraction analysis. Hirshfeld surface analysis was also carried out for identifying short interatomic interactions. The major interactions H…H, O…H and C…H cover the Hirshfeld surface of H-AHMB. The metal complexes [M(AHMB)n] where M = Co(II), Ni(II), Cu(II) and Zn(II) were prepared from metal chlorides and H-AHMB ligand. The bonding was unambigously assigned using FTIR and UV/vis analysis. The synthesized ligand H-AHMB and its metal complexes were studied for ß-glucuronidase enzyme inhibition. Surprisingly the metal complexes were found more active than the parent ligand and even the standard drug. Zn-AHMB shown IC50 = 17.3 ± 0.68 µM compared to IC50 = 45.75 ± 2.16 µM shown by D-saccharic acid-1,4-lactone used as standard. The better activity by Zn-AHMB implying zinc based metallodrug for the treatment of diseases associated with ß-glucuronidase enzyme. The DPPH radical scavenging activities were also studied for all the synthesized compounds. The Co-AHMB complex with IC50 = 98.2 ± 1.78 µM was the only candidate to scavenge the DPPH free radicals.

Response to carvacrol monoterpene in the emergence of Allium cepa L. seeds exposed to salt stress.

Abiotic stresses including sodium chloride (NaCl) are known to negatively affect plant physiology and seed germination by inducing a delay in establishing seedling emergence. The monoterpene carvacrol is the major component of several aromatic plants and seems to interfere with germination and seedling growth. In this study, we investigated whether treatment with carvacrol attenuates the effects of NaCl on the germination and development of Allium cepa, where biochemical parameters were also analyzed. The results showed that the Emergency Speed Index (ESI) was near to 2.0 in the control group. The groups NaCl, carvacrol alone, and in co-treatment with NaCl exhibited an ESI below 0.8, being significantly smaller when compared to the control. NaCl + carvacrol significantly inhibited seed emergence in relation to the NaCl group. Only the content of malondialdehyde was significantly altered by NaCl.

Novel benzimidazole derivatives as effective inhibitors of prolyl oligopeptidase: synthesis, in vitro and in silico analysis.

Background: This research aims to discover novel derivatives having potential therapeutic applications in treating conditions related to prolyl oligopeptidase (POP) dysfunction. Method: Novel benzimidazole derivatives have been synthesized, characterized and screened for their in vitro POP inhibition. Results: All these derivatives showed excellent-to-good inhibitory activities in the range of IC50 values of 3.61 ± 0.15 to 43.72 ± 1.18 µM, when compared with standard Z-prolyl-prolinal. The docking analysis revealed the strong interactions between our compounds and the target enzyme, providing critical insights into their binding affinities and potential implications for drug development. Conclusion: The significance of these compounds in targeting POP enzyme offers promising prospects for future research in the field of neuropharmacology.

Effects of Beta Lactams on Behavioral Outcomes of Substance Use Disorders: A Meta-Analysis of Preclinical Studies.

INTRODUCTION: Preclinical studies demonstrated that beta-lactams have neuroprotective effects in conditions involving glutamate neuroexcitotoxicity, including substance use disorders (SUDs). This meta-analysis aims to analyze the existing evidences on the effects of beta-lactams as glutamate transporter 1 (GLT-1) upregulators in animal models of SUDs, identification of gaps in the literature, and setting the stage for potential translation into clinical phases. METHODS: Meta-analysis was conducted on preclinical studies retrieved systematically from MEDLINE and ScienceDirect databases. Abused substances were identified by refereeing to the National Institute on Drug Abuse (NIDA). The results were quantitatively described with a focus on the behavioral outcomes. Treatment effect sizes were described using standardized mean difference, and they were pooled using random effect model. I2-statistic was used to assess heterogeneity, and Funnel plot and Egger's test were used for assessment of publication bias. RESULTS: Literature search yielded a total of 71 studies that were eligible to be included in the analysis. Through these studies, the effects of beta-lactams were evaluated in animal models of nicotine, cannabis, amphetamines, synthetic cathinone, opioids, ethanol, and cocaine use disorders as well as steroids-related aggressive behaviors. Meta-analysis showed that treatments with beta-lactams consistently reduced the pooled undesired effects of the abused substances in several paradigms, including drug-self administration, conditioned place preference, drug seeking behaviors, hyperlocomotion, withdrawal syndromes, tolerance to analgesic effects, hyperalgesia, and hyperthermia. CONCLUSION: This meta-analysis revealed that enhancing GLT-1 expression in the brain through beta-lactams seemed to be a promising treatment approach in the context of substance use disorders, as indicated by results in animal models.

Unveiling the potential of perampanel and pregabalin in addressing pentylenetetrazole-induced electrographic alterations and neurobehavioral anomalies.

Chemical kindling is broadly used experimental model to investigate novel treatments on the process of epileptogenesis and coexisting behavioral comorbidities. The current study aimed to investigate the low dose perampanel (PER) (0.125 and 0.5 mg/kg) and pregabalin (PG) (15 mg/kg) as standalone treatments and in combination on kindling-induced seizure progression with concurrent electroencephalographic alterations. Mice were subjected to pentylenetetrazole (PTZ)-induced kindling followed by neurobehavioral assessment for anxiety-like activity and cognitive deficit through behavioral experiments. The monotherapy with PER at 0.5 mg/kg and PG at 15 mg/kg delayed the kindling process but PRP+PG yielded pronounced benefits and hindered the development of seizures of higher severity. PER+PG combination relieved the animals from anxiety-like behavior in various employed anxiogenic tests. Furthermore, the kindling-associated cognitive deficit was protected by PER+PG combination as increased alteration behavior, discrimination index and latencies to enter the dark zone were noted in y-maze, object recognition and passive avoidance tests, respectively while shorter escape latencies were noted in water maze. The brain samples of kindled mice had elevated malondialdehyde and reduced catalase, superoxide dismutase and glutathione peroxidase enzymes while treatment with PER and PG combination shielded the mice from heightened kindling-associated oxidative stress. Overall, the findings of the present study illustrate that concurrent administration of PER and PG effectively hindered the process of epileptogenesis by protecting neuronal excitability and brain oxidative stress. The results predict the dominance of PER and PG combination over monotherapy which might serve as an effective novel combination to combat drug resistance and behavioral disorders in epileptic patients.