Development, Statistical Optimization, and Characterization of Resveratrol-Containing Solid Lipid Nanoparticles (SLNs) and Determination of the Efficacy in Reducing Neurodegenerative Symptoms Related to Alzheimer's Disease: In Vitro and In Vivo Study.

Resveratrol (RSV), as a natural polyphenol exhibiting antioxidative properties, is studied in the treatment of neurodegenerative diseases. However, RSV has low oral bioavailability. In this study and in order to overcome the issue, RSV was encapsulated into the solid lipid nanoparticles (SLNs). In this study, RSV-loaded solid lipid nanoparticles (RSV-SLNs) were prepared by the solvent emulsification-evaporation technique, and their physicochemical properties were optimized using Box-Behnken response surface methodology. The morphology of the particles was evaluated using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The neuroprotective effects of the nanoparticles were investigated in animal models using the Morris water maze (MWM). Then after, the rats were sacrificed, their brains were collected, and the extent of lipid peroxidase (LPO) as well as the level of reduced glutathione (GSH) were determined in the hippocampus section samples. Finally, the collected brain tissues were histologically studied. The particle size, polydispersity index (PDI), zeta potential, entrapment efficiency (EE%), and drug loading (DL%) of the optimized nanoparticles were 104.5 ± 12.3 nm, 0.322 ± 0.11, -3.1 ± 0.15 mV, 72.9 ± 5.31% and 14.6 ± 0.53%, respectively. The microscopic images revealed spherically shaped and nonaggregated nanoparticles. The in vivo studies demonstrated higher efficiency of RSV-SLN in the reduction of escape latency time and improvement in the time spent in the target quadrant compared to free RSV. Moreover, it was demonstrated that RSV-SLN posed a higher potency in the reduction of LPO as well as elevation of the GSH levels in the brain samples. The histological studies revealed a decline in neural degeneration and an improvement in the CA1 pyramidal cell morphology. The obtained data revealed that RSV-SLNs caused more reduction in Alzheimer-related symptoms rather than free RSV.

Cardioprotective effect of Vitamin D on cardiac hypertrophy through improvement of mitophagy and apoptosis in an experimental rat model of levothyroxine -induced hyperthyroidism.

BACKGROUND: Mitochondria are known to be involved in mediating the calorigenic effects of thyroid hormones. With an abundance of these hormones, alterations in energy metabolism and cellular respiration take place, leading to the development of cardiac hypertrophy. Vitamin D has recently gained attention due to its involvement in the regulation of mitochondrial function, demonstrating promising potential in preserving the integrity and functionality of the mitochondrial network. The present study aimed to investigate the therapeutic potential of Vitamin D on cardiac hypertrophy induced by hyperthyroidism, with a focus on the contributions of mitophagy and apoptosis as possible underlying molecular mechanisms. METHODS AND RESULTS: The rats were divided into three groups: control; hyperthyroid; hyperthyroid + Vitamin D. Hyperthyroidism was induced by Levothyroxine administration for four weeks. Serum thyroid hormones levels, myocardial damage markers, cardiac hypertrophy indices, and histological examination were assessed. The assessment of Malondialdehyde (MDA) levels and the expression of the related genes were conducted using heart tissue samples. Vitamin D pretreatment exhibited a significant improvement in the hyperthyroidism-induced decline in markers indicative of myocardial damage, oxidative stress, and indices of cardiac hypertrophy. Vitamin D pretreatment also improved the downregulation observed in myocardial expression levels of genes involved in the regulation of mitophagy and apoptosis, including PTEN putative kinase 1 (PINK1), Mitofusin-2 (MFN2), Dynamin-related Protein 1 (DRP1), and B cell lymphoma-2 (Bcl-2), induced by hyperthyroidism. CONCLUSIONS: These results suggest that supplementation with Vitamin D could be advantageous in preventing the progression of cardiac hypertrophy and myocardial damage.

GDF11: An emerging therapeutic target for liver diseases and fibrosis.

Growth differentiation factor 11 (GDF11), also known as bone morphogenetic protein 11 (BMP11), has been identified as a key player in various biological processes, including embryonic development, aging, metabolic disorders and cancers. GDF11 has also emerged as a critical component in liver development, injury and fibrosis. However, the effects of GDF11 on liver physiology and pathology have been a subject of debate among researchers due to conflicting reported outcomes. While some studies suggest that GDF11 has anti-aging properties, others have documented its senescence-inducing effects. Similarly, while GDF11 has been implicated in exacerbating liver injury, it has also been shown to have the potential to reduce liver fibrosis. In this narrative review, we present a comprehensive report of recent evidence elucidating the diverse roles of GDF11 in liver development, hepatic injury, regeneration and associated diseases such as non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), liver fibrosis and hepatocellular carcinoma. We also explore the therapeutic potential of GDF11 in managing various liver pathologies.

Evaluating the Efficacy and Safety of Aflibercept Biosimilar (P041) Compared with Originator Product in Patients with Neovascular Age-Related Macular Degeneration.

OBJECTIVE: To assess the noninferiority of biosimilar aflibercept (P041, CinnaGen) to the originator aflibercept (AFL, Regeneron) in terms of efficacy, safety, and immunogenicity. DESIGN: This was a phase Ш, 52-week, multicenter, randomized, double-masked, and active control trial involving eyes in a 1:1 ratio. SUBJECTS: Patients with active subfoveal choroidal neovascularization secondary to age-related macular degeneration randomized into the 2 groups of P041 and AFL. METHODS: Patients received an injection of aflibercept every 4 weeks for 3 doses, followed by administration every 8 weeks up to week 48. MAIN OUTCOME MEASURES: The primary outcome was the noninferiority analysis of eyes maintaining vision at week 52. Secondary outcomes included the changes in visual acuity and retinal thickness, safety evaluation, and immunogenicity during the study. RESULTS: In total, 168 eyes of 168 patients were included. At week 52, the proportion of patients maintaining vision was 94.44% in the P041 group compared with 94.52% in the AFL group. The 95% confidence interval (CI) for the difference of maintaining vision from baseline did not exceed the predefined noninferiority margin of 10% (difference, -0.0008; 95% CI, -0.074 to 0.074; P = 0.98). Secondary outcomes indicated similar results in both arms (all P > 0.05). Safety measured outcomes and immunogenicity were similar between the 2 study groups. CONCLUSIONS: Biosimilar aflibercept was noninferior to AFL in eyes with neovascular age-related macular degeneration. Other efficacy and safety findings also indicated the similarity of 2 products. FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Comparison of low-level laser therapy and standard treatment for temporomandibular disorders: An assessment of therapeutic and placebo effects.

BACKGROUND: Despite extensive research on the use of low-power lasers for TMD treatment, the extent of their effectiveness remains uncertain. OBJECTIVE: This study aimed to investigate the therapeutic or placebo effect of LLLT for TMD, and to compare it with standard treatment methods. A unique aspect of this study was the inclusion of a control group that received only standard treatment, allowing for an assessment of the placebo effect of LLLT. METHODS: A total of 42 patients with TMD were referred to Kerman Dental School Pain Clinic and were randomly assigned to three groups: group A received LLLT, group B was a placebo group and group C was a control group that received only standard treatment. The laser groups received gallium-aluminium-arsenide laser treatment twice a week for 10 sessions. Patients' jaw movement rate indicators and VAS index were evaluated at the start of treatment, and indicators were re-recorded every week for 5 weeks. SPSS 21 was used for statistical analysis, including ANOVA and Tukey's post hoc tests for inter-group comparisons. The repeated measurement test was used to analyse the data. RESULTS: All groups showed significant improvement in VAS indicators (p = .0001), lateral jaw movements (p = .0001), forward jaw movement (p = .007) but not for maximum mouth opening. No significant difference was observed between the groups at the end of the study (p = .000). CONCLUSION: Our study provides insights into LLLT's effectiveness for TMD, suggesting it cannot replace standard treatment alone. These findings contribute to the literature and emphasise the importance of including a control group in future studies to assess the placebo effect of LLLT.

Mitochondrial biogenesis and apoptosis as underlying mechanisms involved in the cardioprotective effects of Gallic acid against D-galactose-induced aging.

BACKGROUND: Aging is a main risk factor for the development of cardiovascular diseases (CVDs). Gallic acid (GA) is a phenolic compound derived from a wide range of fruits. GA has a wide spectrum of pharmacological properties, including anti-oxidative, anti-inflammatory, and cardioprotective effects. This research was conducted to determine the cardioprotective effect of GA on cardiac hypertrophy in aged rats. METHODS AND RESULTS: Following histological evaluation and through observing the heart, we found that GA improved the cardiac hypertrophy induced by D-galactose (D-GAL) in cardiac cells. To clarify the causes for this anti-aging effect, we evaluated the malonic dialdehyde levels and antioxidant enzyme activity in rat cardiac tissue. The levels of lactate dehydrogenase (LDH) and creatine kinase (CK-MB) in serum were measured. The levels of genes related to mitochondrial biogenesis, mitophagy, and apoptosis in cardiac tissue were surveyed. The findings represented that GA ameliorated antioxidant enzyme activity while significantly decreasing the malonic dialdehyde levels. Real-time PCR analysis proposed that GA effectively improved mitochondrial biogenesis in the heart via regulating the expression levels of Sirtuin 1 (SIRT1), PPARγ coactivator 1α (PGC1-α), nuclear factor erythroid 2-related factor 2 (Nrf2), and mitochondrial transcription factor A (TFAM). GA also mitigated apoptosis in the heart by modulating the expression levels of B-cell lymphoma protein 2 (Bcl-2) and Bcl-2-associated X (Bax). In addition, GA improved serum LDH and CK-MB levels. CONCLUSIONS: GA may alleviate aging-induced cardiac hypertrophy via anti-oxidative, mitoprotective, and anti-apoptotic mechanisms.

Acute oral toxicity assessment of galbanic acid in albino rat according to OECD 425 TG.

In spite of the broad biological and also anticarcinogenic effects which have been reported for galbanic acid in various studies, its toxic effects are not still well characterized. The study was accomplished to evaluate the acute oral toxicity of galbanic acid pursuant to Organisation for Economic Co-operation and Development (OECD) TG No. 425. Female rats were received asafoetida extract and galbanic acid in distilled water by oral gavage. According to the existing information, limit test was done for aqueous extract of asafoetida and main test was done for galbanic acid. The animals were monitored for 2 weeks. Then under general anesthesia, the blood samples were obtained from the heart for biochemical and hematological assessment and the vital organs of rats were isolated for pathological evaluation. The results showed that although the Median lethal dose (LD50) of asafoetida extract was above the 2000 mg/kg body weight, the galbanic acid estimated LD50 was 310.2 mg/kg. There was no considerable change in body weight of vehicle and extract treated animals but in galbanic acid treated animals, the body weights were not normally increased. A significant rise was observed in high-density lipoprotein (HDL), (aspartate aminotransferase) AST and (alanine aminotransferase) ALT levels as well as in white blood cells (WBC), platelet and lymphocytes counts in galbanic acid group compared to vehicle and extract groups. Based on the obtained results, we suggest that although the asafoetida aqueous extract could be categorized as group 5 (LD50 > 2000 mg/kg), but galbanic acid estimated LD50 is about 310.2 mg/kg and toxicity signs also appeared in lung, liver enzymes and complete blood count (CBC) of galbanic acid treated animals.

Validation and reliability of the Persian version of the Zurich Claudication Questionnaire in patients with lumbar spinal stenosis.

Background: One of the applicable tools introduced as a specific tool for assessing claudication in patients with lumbar spinal stenosis is the Zurich Claudication Questionnaire (ZCQ). This questionnaire has been validated in different populations of patients. The present study aimed to determine the validation status of the Persian version of ZCQ. Methods: After professional translation of the ZCQ by native English translators, it was executed twice before surgery with 1 day interval on 45 Iranian patients with spinal stenosis. The reliability was assessed by determining the Chronbach's Alpha coefficient as well as intraclass correlation coefficient (ICC). To assess the concurrent validity, the correlation across the 3 domains of the questionnaire was calculated by the Pearson's correlation test and the content validity was determined using a panel of experts. Results: To assess test-retest reliability, the ICC for ZCQ for symptom severity, functional disability, and satisfaction domains were 0.80, 0.82, and 0.78, indicating acceptable reliability. Regarding internal consistency, Cronbach's alpha coefficients for the Persian version of ZCQ for the 3 above domains were shown to be 0.96, 0.92, and 0.90 respectively. On the subject of content validity, the 3 questionnaire's domains were marked as relevant with the content validity indices of 0.88, 0.82, and 0.80 respectively. Concerning concurrent validity, all 3 domains of the Persian ZCQ correlated strongly with 1 another. Conclusions: The ZCQ questionnaire with the same original structure is completely functional and reliable in the Iranian patient community.

Toxicity of para-phenylenediamine (PPD;1, 4 diaminobenzene) on isolated human lymphocytes: The key role of intracellular calcium enhancement in PPD-induced apoptosis.

Para-phenylenediamine (PPD) is a derivative of benzene used as an ingredient in dyes, a photographic developing agent, and a component of engineered polymers. The carcinogenicity of PPD, which has been documented in several studies, may be related to its toxic effects on different compartments of the immune system. The main goal of this research was to evaluate the mechanism of the toxicity of PPD on human lymphocytes by exploiting the accelerated cytotoxicity mechanism screening (ACMS) technique. Lymphocytes were isolated from the blood of healthy persons using a Ficoll-Paque PLUS standard method. Assessment of cell viability was carried out 12 h following treatment of human lymphocytes with 0.25-1 mM PPD. For determination of cellular parameters, isolated human lymphocytes were incubated with 1/2 the IC50 (0.4 mM), the IC50 (0.8 mM), and twice the IC50 (1.6 mM) for 2, 4, and 6 h. Half maximal inhibitory concentration (IC50) is the concentration that reduces cell viability approximately 50% following treatment. The results of this study demonstrated that PPD-associated apoptosis in human lymphocytes was mainly through the enhancement of intracellular calcium, oxidative stress, and following adverse effect on lymphocyte organelles (like mitochondria and lysosomes). Lipid peroxidation, activation of caspase-3, and stimulation of cytokines (IL2, interferon-gamma (IFN-γ), and TNF-alpha) production were also observed in PPD-treated lymphocytes. Considering the results of this study, we can suggest an association between PPD carcinogenicity and its toxic effects on different compartments of the immune system.

The effect of infusion time on Echium amoenum extract -induced hepatotoxicity in vitro.

Echium amoenum is an annual herb native to the northern mountains of Iran which has medicinal application. Petals of Echium amoenum (Gole-Gavzaban) is one of the most valuable medicinal plants in Iranian folk medicine. The dry petals of E. amoenum have long been used as a sedative, tonic, anxiolytic and as a treatment for sore throat, cough and inflammation. Previous studies have shown that petals of E. amoenum contain four toxic pyrrolizidine alkaloids but conflicting results have been acquired in experimental studies investigating the hepatotoxicy of E. amoenum. However, the direct effect of E. amoenum on liver cells and the complete mechanisms of its possible cytotoxic effects toward these cells remain to be defined. The main aim of this study was to assay the mechanisms underlying the toxic effects of E. amoenum toward hepG2 cells. E. amoenum extract was obtained by infusion of dried petals in hot water (90 centigrade) for 15 or 30 min. Cell viability and mechanistic parameters were determined following 12 h incubation of hepG2 with E. amoenum extract that was obtained after 15 or 30 min infusion. The results indicated that E. amoenum extract exerts cytotoxic effects on hepG2 cells, probably through mitochondrial and lysosomal damage induced by glutathione depletion and oxidative stress.

Solitary Plasmacytoma of the Mandible: A Case Report.

Plasmacytoma is an abnormal proliferation of monoclonal B-cells, and it can occur in several forms including multiple myeloma, solitary plasmacytoma of the bone, and extramedullary plasmacytoma primary. The solitary plasmacytoma of the bone accounts for about 3-10% of all plasma cell neoplasms, and occurs most often in the vertebrae, whereas the solitary plasmacytoma of the mandible is an extremely rare occurrence. This case report presents a 61-year-old woman with various underlying diseases diagnosed with solitary plasmacytoma of the mandible. This case is very well documented with radiographic imagery, clinical, and histopathological findings.

Regulatory effects of trimetazidine in cardiac ischemia/reperfusion injury.

Ischemia/reperfusion (I/R) injury is a tissue damage during reperfusion after an ischemic condition. I/R injury is induced by pathological cases including stroke, myocardial infarction, circulatory arrest, sickle cell disease, acute kidney injury, trauma, and sleep apnea. It can lead to increased morbidity and mortality in the context of these processes. Mitochondrial dysfunction is one of the hallmarks of I/R insult, which is induced via reactive oxygen species (ROS) production, apoptosis, and autophagy. MicroRNAs (miRNAs, miRs) are non-coding RNAs that play a main regulatory role in gene expression. Recently, there are evidence, which miRNAs are the major modulators of cardiovascular diseases, especially myocardial I/R injury. Cardiovascular miRNAs, specifically miR-21, and probably miR-24 and miR-126 have protective effects on myocardial I/R injury. Trimetazidine (TMZ) is a new class of metabolic agents with an anti-ischemic activity. It has beneficial effects on chronic stable angina by suppressing mitochondrial permeability transition pore (mPTP) opening. The present review study addressed the different mechanistic effects of TMZ on cardiac I/R injury. Online databases including Scopus, PubMed, Web of Science, and Cochrane library were assessed for published studies between 1986 and 2021. TMZ, an antioxidant and metabolic agent, prevents the cardiac reperfusion injury by regulating AMP-activated protein kinase (AMPK), cystathionine-γ-lyase enzyme (CSE)/hydrogen sulfide (H2S), and miR-21. Therefore, TMZ protects the heart against I/R injury by inducing key regulators such as AMPK, CSE/H2S, and miR-21.

The Impact of Rigid Cervical Collars on Outcome of Patients Who Underwent Posterior Cervical Laminectomy and Fusion: A Retrospective Comparative Study.

STUDY DESIGN: Retrospective cohort study. PURPOSE: This study aimed to investigate the cervical collar impact on the functional outcomes of patients after posterior cervical laminectomy and lateral mass screw fixation (PCLF) surgery. OVERVIEW OF LITERATURE: The safety and possible benefits of implementing rigid cervical collars subsequent to PCLF are insufficiently investigated. METHODS: Patients who underwent PCLF and received postoperative cervical collars from 2018 to 2020 were included in this retrospective cohort study. Their data were compared with an age- and sex-matched group of subjects who did not receive collars after PCLF during the same period. Pain intensity (using the Visual Analog Scale), Neck Disability Index, and quality of life (using 36-item Short Form Health Survey) of the patients were compared at baseline, 1, 3, 6, and 12 months postoperatively. RESULTS: A total of 36 patients who received cervical collars after surgery and 40 controls were included. At baseline and 1-month follow-up, there were no differences in pain intensity, functional status, and quality of life between the groups. However, at 3 months postoperatively, the quality of life of the subjects with no orthosis was higher than those who received cervical collars (p =0.01). At 6- and 12-month follow-up, there were no differences between the groups in pain intensity, functional status, and quality of life. CONCLUSIONS: No difference in the pain intensity and functional status of patients who used cervical collars and controls was shown in our study. Patients who did not wear cervical collars had a higher quality of life during the 3-month postoperative evaluation. Future prospective, well-controlled studies with longer follow-ups are needed to further investigate the effects of cervical orthosis on the clinical outcome of patients after PCLF.

Royal jelly improves learning and memory deficits in an amyloid ß-induced model of Alzheimer's disease in male rats: Involvement of oxidative stress.

Alzheimer's disease (AD) as the commonest type of dementia is associated with the cognitive function failure. Oxidative stress performs an essential role in the progression of AD. Royal jelly (RJ) is a natural product of bees with antioxidant and anti-inflammatory properties. The present research aimed to investigate the possible protective effect of RJ on learning and memory in a rat model of Aß-induced AD. Forty male adult Wistar rats were equally distributed into five groups: control, sham-operated, Aß (receiving intracerebroventricular (ICV) injection of amyloid beta (Aß1-40)), Aß + RJ 50 mg/kg, and Aß + RJ 100 mg/kg. RJ was administered daily post-surgery by oral gavage for four weeks. Behavioral learning and memory were examined using the novel object recognition (NOR) and passive avoidance learning (PAL) tests. Also, oxidative stress markers, such as malondialdehyde (MDA), total oxidant status (TOS) and total antioxidant capacity (TAC), were assessed in the hippocampus. Aß reduced step-through latency (STLr) and increased time spent in the dark compartment (TDC) in the PAL task and also decreased discrimination index in the NOR test. Administration of RJ ameliorated the Aß-related memory impairment in both NOR and PAL tasks. Aß decreased TAC and increased MDA and TOS levels in the hippocampus, whereas RJ administration reversed these Aß-induced alterations. Our results indicated that RJ has the potential to ameliorate learning and memory impairment in the Aß model of AD via attenuating oxidative stress.

Effect of Topical Administration of Tranexamic Acid on Intraoperative and Postoperative Blood Loss during Posterior Cervical Laminectomy and Fusion Surgery: A Retrospective Study.

AIM: To assess the role of topical administration of tranexamic acid (TXA) on intraoperative and postoperative blood loss of patients undergoing posterior cervical laminectomy and lateral mass screw ?xation (PCLF) compared to a control group. MATERIAL AND METHODS: The data of 88 patients that underwent PCLF surgery, including 41 females and 47 males, were included in this retrospective study. Data elements including intraoperative blood loss (IBL), postoperative blood loss (PBL), amount of blood transfusion, surgical time, use of hemostatic agents, length of hospital stay, and time to return to work were extracted from medical records and compared between those who received topical TXA during surgery (irrigation of the surgical field with a solution of 3 g TXA in 100 ml normal saline) and an age- and sex-matched control group. RESULTS: There were 48 patients in the TXA group and 40 patients in the control group. There were no significant differences in the baseline measurements and the level of operation between the two groups. The results showed that IBL and PBL were significantly lower in the TXA group compared to the control group (p=0.03 and p < 0.01, respectively). There were no significant differences in the need for blood transfusion, surgical time, and hospital stay between the two groups (p > 0.05). Moreover, the use of hemostatic materials during surgery and the time to return to work were significantly lower in the topical TXA group (p=0.04 and p < 0.01, respectively). CONCLUSION: Topical TXA efficiently reduces intraoperative and postoperative bleeding in patients undergoing posterior cervical laminectomy and PCLF surgery. These results need further investigation in future studies to draw a definite conclusion.

The role of FGF21 and its analogs on liver associated diseases.

Fibroblast growth factor 21 (FGF21), a member of fibroblast growth factor family, is a hormone-like growth factor that is synthesized mainly in the liver and adipose tissue. FGF21 regulates lipid and glucose metabolism and has substantial roles in decreasing lipogenesis and increasing hepatic insulin sensitivity which causing lipid profile improvement. FGF21 genetic variations also affect nutritional and addictive behaviors such as smoking and alcohol consumption and eating sweets. The role of FGF21 in metabolic associated diseases like diabetes mellitus had been confirmed previously. Recently, several studies have demonstrated a correlation between FGF21 and liver diseases. Non-alcoholic fatty liver disease (NAFLD) is the most prevalent type of chronic liver disease worldwide. NAFLD has a wide range from simple steatosis to steatohepatitis with or without fibrosis and cirrhosis. Elevated serum levels of FGF21 associated with NAFLD and its pathogenesis. Alcoholic fatty liver disease (AFLD), another condition that cause liver injury, significantly increased FGF21 levels as a protective factor; FGF21 can reverse the progression of AFLD and can be a potential therapeutic agent for it. Also, NAFLD and AFLD are the most important risk factors for hepatocellular carcinoma (HCC) which is the fourth deadliest cancer in the world. Several studies showed that lack of FGF21 induced oncogenic condition and worsened HCC. In this review article, we intend to discuss different aspects of FGF21 in NAFLD, AFLD and HCC; including the role of FGF21 in pathophysiology of these conditions, the effects of FGF21 mutations, the possible use of the FGF21 as a biomarker in different stages of these diseases, as well as the usage of FGF21 and its analog molecules in the treatment of these diseases.

Impairment in social interaction and hippocampal long-term potentiation at perforant pathway-dentate gyrus synapses in a prenatal valproic acid-induced rat model of autism.

It is well established that prenatal valproic acid exposure in rats leads to autism-like behaviours and social deficits. Long-term potentiation changes in the brain have been proposed as a potential mechanism in the development of autistic behaviour. However, there are controversies regarding the effect of in utero valproic acid exposure on long-term potentiation. This study examined the social interaction and long-term potentiation induction in perforant pathway-dentate gyrus synapses in male offspring of a rat model of autism induced by prenatal exposure to valproic acid. On Embryonic Day 12.5, the pregnant dams received an injection of 500 mg/kg valproic acid (intraperitoneal) to produce the autism model. The sociability test was performed between Postnatal Days 37 and 40. The offsprings were urethane-anaesthetized and placed into a stereotaxic apparatus for surgery, electrode implantation and field potential recording on Postnatal Days 45-55. In the dentate gyrus region, excitatory postsynaptic potential slope and population spike amplitude were measured. Valproic acid-exposed offspring showed significantly impaired social interaction. The birth weight in valproic acid-exposed rats was significantly lower than in control rats. The ability of dentate gyrus synapses to induce long-term potentiation was hampered by valproic acid exposure. The decreasing excitatory postsynaptic potential slope and population spike amplitude of long-term potentiation provide evidence in favour of this notion. It is widely supposed that the hippocampus plays a central role in the process of learning and memory as well as social interaction and social memory. Therefore, deficiencies in hippocampal synaptic plasticity may be responsible, at least in part, for the social interaction deficits in valproic acid-exposed rats.

Identification, molecular docking, and kinetic studies of six novel angiotensin-I-converting enzyme (ACE) inhibitory peptides derived from Kenaf (Hibiscus cannabinus L.) seed.

Kenaf (Hibiscus cannabinus L.) seed is a valuable protein source that could be used to prepare protein hydrolysates with antihypertensive properties. However, the potential of using kenaf seeds for health food and pharmaceutical applications has not been fully exploited. Thus, the aim of this study was to identify and characterise the Angiotensin-I-Converting Enzyme (ACE) inhibitory peptides derived from the optimized hydrolysis conditions of kenaf seed protein hydrolysates (KSPH). The optimum hydrolysis conditions determined by response surface methodology (RSM) were as follows: temperature 65 °C, pH 6.5, hydrolysis time 2.25 h, and enzyme/substrate (E/S) ratio of 0.03 (w/w). Under these conditions, the degree of hydrolysis (DH) was 55.28 % and ACE inhibitory activity was 75.51 %. Also, the low molecular weight peptide fractions, <2 kilodalton (kDa) and 2-5 kDa showed the highest ACE-inhibitory activity (82.27 % and 83.69 %, respectively). The 2-5 kDa fraction by Quadrupole-Time-of-Flight Liquid Chromatography-Mass Spectrometry (QTOF LC - MS) revealed the abundance of six peptides, LYWSYLYN, ALFYWVS, LLLHAL, AKSCVVFP, INPPSTTN, and WTIPTPS. Kinetic studies showed that peptide LYWSYLYN possessed the highest Michaelis constant (Km), maximum velocity (Vmax) values and the lowest inhibitor constant (Ki) values, suggesting of its superior ACE inhibitory activity compared to other peptides.

Bioflavonoid exerts analgesic and antiinflammatory effects via transient receptor potential 1 channel in a rat model / Bioflavonoide exerce efeitos analgésicos e antiinflamatórios via canal receptor do potencial transitório 1 em um modelo de rato

Abstract Background Pain is an uncomfortable sensation in the body. Kaempferol is a flavonoid with antinociceptive effects. Transient receptor potential (TRP) channels have been characterized in the sensory system. Objective This study evaluated the central antinociceptive effect of Kaempferol and possible mechanisms of action of transient receptor potential cation channel subfamily V member 1 (TRPV1). Methods Capsaicin as a TRPV agonist (5 μg/μL, intracerebroventricular [ICV]) and capsazepine as its antagonist (10 μg/μL, icv) were used to test the analgesic effect of kaempferol (1.5 mg, ICV). Morphine (10 μg, ICV) was used as a positive control. The other groups were treated with a combination of kaempferol and capsaicin, kaempferol and capsazepine, and capsaicin and capsazepine. The cannula was implanted in the cerebroventricular area. The tail-flick, acetic acid, and formalin tests were used to assess analgesic activity.For evaluation of antiinflammatory effect, the formalin-induced rat pawedema was used. Results Kaempferol significantly decreased pain in the acute pain models, including the tail-flick and the first phase of the formalin test. In the late phase of the formalin test, as a valid model of nociception, capsazepine inhibited the antinociceptive effect of kaempferol. Conclusions Kaempferol has an analgesic effect in the acute pain model and can affect inflammatory pain. Also, the TRPV1 channel plays a role in the antinociceptive activity of kaempferol.

Resumo Antecedentes A dor é uma sensação desconfortável no corpo. Kaempferol é um flavonoide com efeitos antinociceptivos. Canais receptores de potencial transitório têm sido caracterizados no sistema sensorial. Objetivo Este estudo avaliou o efeito antinociceptivo central do kaempferol e os possíveis mecanismos de ação do TRPV1. Métodos Capsaicina como agonista de TRPV (5 μg/μL, intracerebroventricular [ICV]) e capsazepina como seu antagonista (10 μg/μL, icv) foram usados para testar o efeito analgésico do kaempferol (1,5 mg, ICV). A morfina (10 μg, ICV) foi usada como controle positivo. Os outros grupos foram tratados com uma combinação de kaempferol e capsaicina, kaempferol e capsazepina e capsaicina e capsazepina. A cânula foi implantada na área cerebroventricular. Os testes de movimento de cauda, ácido acético e formalina foram usados para avaliar a atividade analgésica. Para avaliação do efeito anti-inflamatório, foi utilizado o edema de pata de rato induzido por formalina. Resultados Kaempferol diminuiu significativamente a dor nos modelos de dor aguda, incluindo o movimento da cauda e a primeira fase do teste de formalina. Na fase tardia do teste da formalina, como modelo válido de nocicepção, a capsazepina inibiu o efeito antinociceptivo do kaempferol. Conclusões Kaempferol tem efeito analgésico no modelo de dor aguda e pode afetar a dor inflamatória. Além disso, o canal TRPV1 desempenha um papel na atividade antinociceptiva do kaempferol.

Non-cystic macular thickening on optical coherence tomography as an alternative to fluorescein angiography for predicting retinal vascular leakage in early stages of uveitis.

To evaluate the relationship between non-cystic thickening of the macula on optical coherence tomography (OCT) and retinal vascular leakage on fluorescein angiogram (FA) in patients with uveitis. A cross-sectional study of patients seen in the uveitis clinic. Patients with any degree of inflammatory cells in the anterior vitreous were included, provided that no macular cyst or subretinal fluid or macular atrophy was observed in OCT. The correlation between OCT features and best corrected visual acuity (BCVA), the degree of inflammation, and FA findings were examined. The severity of vascular leakage in FA was graded for optic nerve, macula and posterior and peripheral leakage. We used generalized estimation equation to assess the associations between macular thickness and volume with angiographic scores. A total of 43 patients (100 exam data) met inclusion criteria. There was a significant relationship between OCT parameters (central macular thickness, 3 mm and 6 mm perifoveal macular thickness as well as total and central macular volume) with angiographic scores (macular, optic disc, posterior and peripheral vascular leakage score) (all P values < 0.0001). The correlation between the 6 mm perifoveal thickness and peripheral vascular leakage score (R = 0.76; P < 0.001) was stronger than the correlation of CMT with this angiographic score (R = 0.69; P < 0.001). Non-cystic thickening of the macula on OCT, especially in perifoveal area, is a reliable predictor of the presence of retinal vascular leakage in patients with uveitis.