The influence of propolis plus Hyoscyamus niger L. against COVID-19: A phase II, multicenter, placebo-controlled, randomized trial.

The incubation period of COVID-19 symptoms, along with the proliferation and high transmission rate of the SARS-CoV-2 virus, is the cause of an uncontrolled epidemic worldwide. Vaccination is the front line of prevention, and antiinflammatory and antiviral drugs are the treatment of this disease. In addition, some herbal therapy approaches can be a good way to deal with this disease. The aim of this study was to evaluate the effect of propolis syrup with Hyoscyamus niger L. extract in hospitalized patients with COVID-19 with acute disease conditions in a double-blinded approach. The study was performed on 140 patients with COVID-19 in a double-blind, randomized, and multicentral approach. The main inclusion criterion was the presence of a severe type of COVID-19 disease. The duration of treatment with syrup was 6 days and 30 CC per day in the form of three meals. On Days 0, 2, 4, and 6, arterial blood oxygen levels, C-reactive protein (CRP), erythrocyte sedimentation rate, and white blood cell, as well as the patient's clinical symptoms such as fever and chills, cough and shortness of breath, chest pain, and other symptoms, were recorded and analyzed. Propolis syrup with H. niger L. significantly reduces cough from the second day, relieving shortness of breath on the fourth day, and significantly reduces CRP, weakness, and lethargy, as well as significantly increased arterial blood oxygen pressure on the sixth day compared to the placebo group (p < 0.05). The results in patients are such that in the most severe conditions of the disease 80% < SpO2 (oxygen saturation), the healing process of the syrup on reducing CRP and increasing arterial blood oxygen pressure from the fourth day is significantly different compared with the placebo group (p < 0.05). The use of syrup is associated with a reduction of 3.6 days in the hospitalization period compared with the placebo group. Propolis syrup with H. niger L. has effectiveness in the viral and inflammatory phases on clinical symptoms and blood parameters and arterial blood oxygen levels of patients with COVID-19. Also, it reduces referrals to the intensive care unit and mortality in hospitalized patients with COVID-19. So, this syrup promises to be an effective treatment in the great challenge of COVID-19.

The effect of risperidone on behavioral reactions and gene expression of pro- and anti-inflammatory cytokines in neuropathic pain model induced by chronic constriction injury of the sciatic nerve in rat.

BACKGROUND: Neuropathic pain results from lesions or diseases affecting the somatosensory system. The management of a patient with chronic neuropathic pain remains a challenge several studies report the analgesic effect of serotonin receptor antagonists in different models of experimental pain. The present study was designed to study the effect of systemic administration of risperidone, on behavioral scores of neuropathic pains in chronic constriction (CCI) model in rats. METHODS: Inducing neuropathic pain with the CCI model which causes heat hyperalgesia, heat, and mechanical allodynia was performed on rats, and then, in two phases, risperidone effect was determined. In the acute phase, risperidone 1, 2, 4 mg was administered for three groups half an hour before behavioral tests on the 7th, 14th, and 21st day after surgery, and in the chronic phase, risperidone 1, 2, and 4 mg was administered for three different groups from the 1st to 14th days after surgery than on 14th-day behavioral scores were performed. For gene expression analysis, samples are taken from spinal cord tissues in lumbar segments. RESULTS: This study shows chronic administration of risperidone as an antipsychotic drug was effective on heat hyperalgesia and allodynia. However, only the max dosage (4 mg) of risperidone showed meaningful improvement in increasing mechanical allodynia. However, acute administering of risperidone did not show any meaningful changes in behavioral tests on neuropathic pain induced by chronic constriction injury of the sciatic nerve in rats. In addition, gene expression results showed an increase in IL-4 and IL-10 gene expression in the risperidone group compared to the sham group. CONCLUSION: This study suggests the helpful preventive effects of risperidone in developing and increasing neuropathic pain, but it does not have any instant effect.

The Effects of Probiotic Supplementation on Opioid-Related Disorder in Patients under Methadone Maintenance Treatment Programs.

Introduction: Patients under methadone maintenance treatment programs (MMTPs) are susceptible to numerous complications (e.g., mental and metabolic disorders). This study evaluated the effects of probiotics on clinical symptoms, biomarkers of oxidative stress, inflammation, insulin resistance, and serum lipid content in patients receiving MMTPs. Materials and Methods: A randomized, double-blind, placebo-controlled trial was conducted among 70 patients receiving MMTPs to receive either 1.8 × 109 CFU/day probiotics (n = 35) or placebo (n = 35) for 12 weeks. Clinical symptoms and metabolic profiles were measured before and after the intervention in patients receiving MMTPs. Results: Compared with the placebo group, probiotic supplementation resulted in a significant improvement in the severity of depression (P < 0.05). In addition, probiotic administration significantly decreased fasting plasma glucose (FPG), total cholesterol, and low-density lipoprotein cholesterol (LDL cholesterol) (P < 0.05). Furthermore, probiotics resulted in a significant reduction in high-sensitivity C-reactive protein (hs-CRP) and a significant elevation in total antioxidant capacity (TAC) and total glutathione (GSH) levels (P < 0.05). Conclusion: Treatment with probiotics for 12 weeks to patients receiving MMTPs had beneficial effects on symptoms of depression, as well as several metabolic profiles. Clinical Trial Registration: this study was registered in the Iranian website (https://www.irct.ir) for clinical trials registration (https://fa.irct.ir/trial/46363/IRCT20170420033551N9). The registration date is March 22, 2020.

The Effects of Oxytocin on Craving, Mental Health Parameters, and Stress Hormones in Methamphetamine-Dependent Patients Undergoing Matrix Treatment Model: A Randomized, Double-Blind Clinical Trial.

BACKGROUND: Methamphetamine (METH) dependence is an increasing public health problem with a wide range of mental and physical adverse effects. Recent studies report that oxytocin (OXT) has potential therapeutic properties in drug dependence. Hence, the present study was designed to evaluate the effects of OXT on craving, mental health (depression and anxiety), and stress hormones (ACTH and cortisol) in METH-dependent patients undergoing matrix treatment model (MTM), an intensive outpatient approach for stimulant abuse treatment. METHODS: This randomized placebo-controlled clinical trial was conducted in 42 METH-dependent patients undergoing MTM to receive either intranasal OXT 40 IU (n = 21) or normal saline as placebo (n = 21) for 4 weeks. Clinical and biochemical parameters were measured at baseline and end of trials in METH-dependent patients. RESULTS: Our findings indicated that OXT administration for 4 weeks is associated with a significant improvement in the craving and depression scores, respectively (p < 0.001 and p < 0.001), but there was no significant difference for anxiety scores compared with the placebo group. In addition, OXT administration significantly decreased cortisol (p < 0.001) and ACTH levels (p < 0.002). CONCLUSIONS: These findings suggest that OXT can be considered as a new potential therapeutic for the treatment of METH-dependent patients undergoing MTM. Further studies are required to explore the effectiveness and safety of OXT.

The correlation between IgM and IgG antibodies with blood profile in patients infected with severe acute respiratory syndrome coronavirus.

OBJECTIVES: This study aimed to determine the levels of IgM and IgG antibody response to the severe acute respiratory syndrome coronavirus (SARS-CoV)-2 in coronavirus disease 2019 (COVID-19) patients with different disease severity. METHODS: IgM and IgG antibody levels were evaluated via enzyme-linked immunosorbent assay (ELISA). In total, 100 patients with confirmed SARS-CoV-2 infection were enrolled in this study and viral RNA was detected by using Real-time PCR technique. Clinical and laboratory data were collected and analyzed after hospital admission for COVID-19 and two months post-admission. RESULTS: The level of anti-SARS-CoV-2 antibody IgG was significantly higher in the severe patients than those in moderate and mild groups, 2 months after admission. Also, level of IgG was positively associated with increased WBC, NUT and LYM counts in sever than mild or moderate groups after admission to hospital. CONCLUSION: Our findings suggested that patients with severe illness might experience longer virus exposure times and have a stronger antibody response against viral infection. Thus, they have longer time immunity compared with other groups.

The effect of vitamin C on procalcitonin biomarker in community-acquired pneumonia.

INTRODUCTION: Community acquired pneumonia (CAP) is a prevalent low respiratory infection. Diagnosis is based on clinical symptoms, radiologic evidence and culture. Biomarkers such as IL6, CRP and procalcitonin are helpful in diagnosis. Procalcitonin is a soluble biomarker in serum that increase in systemic inflammation and bacterial infections. People with normal procalcitonin have low risk to infect pneumonia. Patient with CAP have more oxidative stress than normal people. Studies show that receiving vitamin C can reduce incidence of pneumonia. The present study was designed to evaluate the effect of vitamin C supplement on procalcitonin biomarker in patient with CAP. METHODS: Patients with CAP who passed inclusion and exclusion criteria after obtaining informed consent, were assigned randomly in two groups of drug and placebo. The drug group received vitamin C (1000 mg/d) daily and medications that physician prescribed for treating CAP for 10 days and placebo group received placebo and medications that physician prescribed. The serum level of procalcitonin was measured at the beginning of the study and after 10 days of intervention. RESULTS: 35 patients finished the study. Serum level of procalcitonin on the first and tenth day did not show any significant difference between drug and placebo groups. CONCLUSIONS: To clarify the relationship between the effects of vitamin C on procalcitonin in CAP, a larger sample size is required.

The effect of crocin (the main active saffron constituent) on the cognitive functions, craving, and withdrawal syndrome in opioid patients under methadone maintenance treatment.

Individuals under methadone maintenance treatment (MMT) programs are susceptible to several complications, including withdrawal syndrome, craving, and cognitive deficits. This study was designed to elevate the effect of crocin administration on withdrawal syndrome, craving, and cognitive function in subjects under MMT programs. It was a clinical trial that was conducted among 60 patients referred to Soltan Mirahmad Clinic for addict patients in Kashan, Iran. The patients were allocated to two groups including placebo and intervention groups. The intervention group received 30 mg/day crocin (n = 30) and placebo (n = 30) once a day, in 12 weeks. Withdrawal syndrome, craving, and cognitive function parameters were measured before and after the intervention in subjects under MMT programs. Compared with the placebo group, crocin resulted in a significant improvement in craving score (p = .03), and withdrawal symptoms score (p = .01) in the intervention group. In addition, crocin supplementation did not affect cognitive function parameters (e.g., TMT, FAS test, and DGSP score). Overall, crocin supplementation for 12 weeks to patients under MMT programs had beneficial effects on craving and withdrawal symptoms score, but did not affect the cognitive function parameters.

The effect of propolis plus Hyoscyamus niger L. methanolic extract on clinical symptoms in patients with acute respiratory syndrome suspected to COVID-19: A clinical trial.

The outbreak of Coronavirus disease 2019 (COVID-19) has caused a global health crisis. Nevertheless, no antiviral treatment has yet been proven effective for treating COVID-19 and symptomatic supportive cares have been the most common treatment. Therefore, the present study was designed to evaluate the effects of propolis and Hyoscyamus niger L. extract in patients with COVID-19. This randomized clinical trial was conducted on 50 cases referred to Akhavan and Sepehri Clinics, Kashan university of medical sciences, Iran. Subjects were divided into two groups (intervention and placebo). This syrup (containing 1.6 mg of methanolic extract along with 450 mg of propolis per 10 mL) was administered three times a day to each patient for 6 days. The clinical symptoms of COVID-19 such as: dry cough, shortness of breath, sore throat, chest pain, fever, dizziness, headache, abdominal pain, and diarrhea were reduced with propolis plus Hyoscyamus niger L. extract than the placebo group. However, the administration of syrup was not effective in the control of nausea and vomiting. In conclusion, syrup containing propolis and Hyoscyamus niger L. extract had beneficial effects in ameliorating the signs and symptoms of COVID-19 disease, in comparison with placebo groups.

Efficacy of Persian medicine herbal formulations (capsules and decoction) compared to standard care in patients with COVID-19, a multicenter open-labeled, randomized, controlled clinical trial.

Persian medicine has recommended clinical experiences and proper herbal remedies for prevention and treatment of microbial infections and respiratory diseases. An open-label, randomized, controlled, multicenter trial was conducted at five hospitals in Tehran and Isfahan provinces of Iran on 358 hospitalized adult patients. A total of 174 patients received standard care and 184 received herbal remedies (polyherbal decoction every 8 hr and two herbal capsules every 12 hr) plus standard care for 7 days. The primary clinical endpoint was the duration of hospital stay, and secondary outcomes were clinical improvement of symptoms based on self-assessment questionnaire. Results demonstrated that these natural decoction and capsules treatment plus routine care significantly decreased duration of hospital dyspnea (3.291 day vs. 6.468 days), accelerated clinical improvement, and decreased symptoms such as dry cough, dyspnea, muscle pain, headache, fatigue, anorexia, chills, runny nose, sputum cough, and vertigo in the treatment group compared with standard-care group. Significant effects of these polyherbal formulations on improving the symptoms of COVID-19 could be incredibly promising for managing this pandemic with acceptable tolerability.

Neuro-Immuno-Endocrine Interactions in Early Life Stress and Heroin Withdrawal Timeline.

Both heroin abuse and early life stress (ELS) affect the immune system and the hypothalamic-pituitary-adrenal (HPA) axis. Additionally, accelerated aging due to mild inflammation has been indicated in these conditions. The present study aims to compare plasma levels of apoptosis markers, inflammatory markers, and stress hormones during early heroin abstinence period. Thirty-one individuals with heroin/opioid use disorder who had heroin-ELS and 26 of their siblings who were not abusing substances (ELS), and 32 individuals with heroin/opioid use disorder without a history of ELS (heroin-no ELS) were included in the study. The levels of interleukin-6, C-reactive protein, erythrocyte sedimentation rate, albumin, alanine transaminase, aspartate transaminase, and white blood cell count were assessed as the inflammatory and biochemistry markers. Also, apoptosis markers including tumor necrosis factor (TNF)-related weak inducer of apoptosis, TNF-related apoptosis-inducing ligand, soluble tumor necrosis factor receptor type I as apoptosis markers were detected by enzyme-linked immunosorbent assay. ELS was simultaneously evaluated using the Childhood Trauma Questionnaire, Minnesota Multiphasic Personality Inventory, and beck depression inventory scales. Besides, heroin craving was assessed by Daily Drinking/Drug Questionnaire score in individuals with heroin use disorder. This is the first study to evaluate the inflammatory, stress, and apoptosis markers during heroin abstinence, supporting the association between ELS and peripheral pro-inflammatory markers' levels and HPA axis.

Anticonvulsant effects of thiamine on pentylenetetrazole-induced seizure in mice.

OBJECTIVES: Thiamine serves as a cofactor for several enzymes involved in brain function and neurotransmitters biosynthesis. Thiamine-dependent enzymes are important for oxidant stress defenses. Several studies have reported that thiamine deficiency in the central nervous system reduces seizure threshold. The present study was designed to investigate the effect of acute and chronic administration of thiamine alone and in combination with sub-effective dose of diazepam on pentylenetetrazole (PTZ)-induced tonic-clonic seizures in mice. METHODS: Animals were randomly divided into control and experimental groups. In experimental groups, thiamine (50, 100, and 200 mg/kg i.p.) was administered acutely or chronically (once a day, for 14 days). Slow intravenous infusion of PTZ (5 mg/ml) by infusion pump with a constant rate (0.3 ml/min) was used to induce clonic and tonic seizures. RESULTS: Acute injection of thiamine (50, 100, and 200 mg/kg i.p.) did not increase seizure threshold significantly, but chronic treatment with thiamine (200 mg/kg i.p.) increases the clonic and tonic seizure threshold. Moreover, the combination of sub-effective dose of thiamine (100 mg/kg) and diazepam (0.1 mg/kg) significantly increased seizure threshold and enhanced the anticonvulsant effect of diazepam at ineffective dose (0.1 mg/kg). DISCUSSION: Our results suggest that thiamine can be considered as a potential add-on treatment in deficient and non-deficient thiamine epileptic patients. Co-administration of this vitamin with classic antiepileptics to decrease the required doses of regular drugs may be recommended. Nevertheless, more well-designed studies may be executed to provide further accurate information.

Vitamin D supplementation attenuates the behavioral scores of neuropathic pain in rats.

Objective(s): Neuropathic pain due to lesion or dysfunction of the peripheral or central nervous system is often refractory to the conventional analgesics. Currently, there is no proven treatment to prevent or cure neuropathic pain. A recent surge of new data suggests the potential effects of vitamin D in the medical community. This study was designed to determine whether acute or chronic vitamin D administration was effective in alleviating symptoms of neuropathic pain in a rat model of neuropathic pain. Materials and Methods: Neuropathic pain was induced by chronic constriction injury (CCI) of the sciatic nerve in the rats that resulted in thermal hyperalgesia, mechanical, and cold allodynia. Results: Acute vitamin D injections (250, 500, and 1000 unit/kg i.p.) on the 7th, 14th, and 21st postoperative days could not attenuate mechanical and cold allodynia as well as heat hyperalgesia compared to CCI group. But when vitamin D (1000 unit/kg i.p.) administration was started on the first day after surgery and given daily until the 21st day, cold allodynia and heat hyperalgesia considerably were attenuated. However, no differences in paw withdrawal thresholds were observed. Conclusion: These results indicate that chronic vitamin D administrations can attenuate the behavioral scores of neuropathic pain in rats.

Clinical and metabolic response to vitamin D plus probiotic in schizophrenia patients.

BACKGROUND: This study determined the effects of a novel combination of vitamin D and probiotic on metabolic and clinical symptoms in chronic schizophrenia. METHODS: This trial was conducted among 60 patients with chronic schizophrenia to receive either 50,000 IU vitamin D3 every 2 weeks plus 8 × 109 CFU/day probiotic (n = 30) or placebo (n = 30) for 12 weeks. RESULTS: Vitamin D and probiotic co-supplementation was associated with a significant improvement in the general (- 3.1 ± 4.7 vs. + 0.3 ± 3.9, P = 0.004) and total PANSS scores (- 7.4 ± 8.7 vs. -1.9 ± 7.5, P = 0.01). Vitamin D and probiotic co-supplementation also significantly increased total antioxidant capacity (+ 51.1 ± 129.7 vs. -20.7 ± 53.3 mmol/L, P = 0.007), and significantly decreased malondialdehyde (- 0.3 ± 0.9 vs. + 0.2 ± 0.4 µmol/L, P = 0.01) and high sensitivity C-reactive protein levels (- 2.3 ± 3.0 vs. -0.3 ± 0.8 mg/L, P = 0.001) compared with the placebo. Moreover, taking vitamin D plus probiotic significantly reduced fasting plasma glucose (- 7.0 ± 9.9 vs. -0.2 ± 9.9 mg/dL, P = 0.01), insulin concentrations (- 2.7 ± 2.3 vs. + 0.4 ± 2.0 µIU/mL, P < 0.001), homeostasis model of assessment-estimated insulin resistance (- 0.8 ± 0.7 vs. + 0.1 ± 0.7, P < 0.001), triglycerides (- 7.8 ± 25.2 vs. + 10.1 ± 30.8 mg/dL, P = 0.01) and total cholesterol levels (- 4.9 ± 15.0 vs. + 5.9 ± 19.5 mg/dL, P = 0.04) and total-/HDL-cholesterol ratio (- 0.1 ± 0.6 vs. + 0.3 ± 0.8, P = 0.04). CONCLUSION: Probiotic and vitamin D for 12 weeks to chronic schizophrenia had beneficial effects on the general and total PANSS score, and metabolic profiles. TRIAL REGISTRATION: This study was retrospectively registered in the Iranian website ( www.irct.ir ) for clinical trials registration ( http://www.irct.ir : IRCT2017072333551N2). 07-31-2017 2.

The effects of melatonin supplementation on mental health, metabolic and genetic profiles in patients under methadone maintenance treatment.

This investigation was designed to determine the effect of melatonin supplementation on mental health parameters, metabolic and genetic profiles in patients under methadone maintenance treatment (MMT). This randomized, double-blind, placebo-controlled, clinical trial was conducted among 54 patients under MMT. Participants were randomly allocated to receive either 10 mg melatonin (2 melatonin capsules, 5 mg each) (n = 26) or placebo (n = 28) once a day, 1 hour before bedtime for 12 weeks. Melatonin supplementation significantly decreased Pittsburgh Sleep Quality Index (ß -4.08; 95 percent CI, -5.51, -2.65; P < 0.001), Beck Depression Inventory index (ß -5.46; 95% CI, -8.92, -2.00; P = 0.003) and Beck Anxiety Inventory index (ß -3.87; 95% CI, -5.96, -1.77; P = 0.001) and significantly increased International Index of Erectile Functions (ß 5.59; 95% CI, 1.76, 9.42; P = 0.005) compared with the placebo. Subjects who received melatonin supplements had significantly lower serum insulin levels (ß -2.53; 95% CI, -4.48, -0.59; P = 0.01), homeostasis model of assessment-insulin resistance (ß -0.56; 95% CI, -1.03, -0.09; P = 0.01) and higher quantitative insulin sensitivity check index (ß 0.01; 95% CI, 0.004, 0.02; P = 0.009) and HDL-cholesterol levels (ß 3.71; 95% CI, 1.77, 5.64; P = 0.002) compared to placebo. Additionally, melatonin intake resulted in a significant reduction in serum high sensitivity C-reactive protein (ß -0.15; 95% CI, -0.27, -0.02; P = 0.02), malondialdehyde (ß -0.31; 95% CI, -0.57, -0.05; P = 0.02) and protein carbonyl (ß -0.06; 95% CI, -0.09, -0.04; P < 0.001). This trial indicated that taking melatonin supplements for 12 weeks by patients under MMT had beneficial effects on their mental health metabolic profiles.

The Effects of Oxytocin on Withdrawal, Craving and Stress Response in Heroin-Dependent Patients: A Randomized, Double-Blind Clinical Trial.

Opioid dependence is an increasing clinical and public health problem. Current pharmacotherapies have limited efficacy and cause serious side effects. Increasing bodies of evidences suggest the neuropeptide, oxytocin (OT), as a potential treatment for drug abuse disorders. The current study was designed to evaluate the effect of OT on withdrawal, craving and anxiety scores, cortisol and dehydroepiandrosterone sulphate (DHEAS) blood level in heroin-dependent male patients. This randomized, double-blind placebo-controlled clinical trial was conducted on 58 males with opioid dependence by Abstinence Center of Addictive People in Iran. The participants were randomly allocated to receive intranasal OT (single dose; 40 IU, n = 29) or placebo (n = 29). Heroine withdrawal, craving and anxiety scores were measured using the Opioid Withdrawal Scale, Visual Analogue Scale and (Desire for Drug Questionnaire), and Hamilton checklist respectively. The cortisol and DHEAS levels at baseline and different post-intervention time were measured using a competitive immunoanalysis method. Acute OT administration reduced craving and withdrawal scores but did not change anxiety significantly. Single dose of OT decreased the level of cortisol and improved the cortisol/DHEAS ratio in the heroin users during abstinence (p < 0.01). These results suggest that OT may be useful in the attenuation of craving, withdrawal symptom in heroin-dependent patients and might be considered a new potential treatment for heroin dependence where positive effects of OT on stress-related hormones may be involved in this effect of OT.

Clinical and metabolic responses to crocin in patients under methadone maintenance treatment: A randomized clinical trial.

Patients under methadone maintenance treatment (MMT) programs are susceptible to several complications including metabolic and clinical disorders. This study was designed to determine the effect of crocin supplementation on mental health parameters and metabolic profiles in subjects under MMT. The current randomized, double-blind, placebo-controlled, clinical trial was conducted among 53 patients under MMT to receive either 15 mg/day of crocin (n = 26) or placebo (n = 27) twice a day for 8 weeks. Crocin administration significantly decreased Beck Depression Inventory score (P = 0.01) and Beck Anxiety Inventory score (P = 0.008) compared with the placebo. In addition, crocin administration resulted in a significant reduction in fasting glucose (P = 0.003), insulin levels (P = 0.01), insulin resistance (P = 0.008), triglycerides (P = 0.001), very low-density lipoprotein (P = 0.001), total cholesterol levels (P = 0.03), and a significant increase in insulin sensitivity (.003) compared with the placebo. Additionally, crocin intake was associated with a significant reduction in high-sensitivity C-reactive protein (p < .001) and malondialdehyde (P = 0.001) and a significant rise in total antioxidant capacity levels (P = 0.01) compared with the placebo. The findings of this clinical trial indicate that taking crocin for 8 weeks by patients under MMT had beneficial effects on their mental health and improved their metabolic profiles.

Sertraline increases the survival of retinoic acid induced neuronal cells but not glial cells from human mesenchymal stem cells.

An increase in the number of viable in vitro differentiated neuronal cells is important for their use in clinics. A proportion of differentiated cells lose their viability before being used, and therefore we decided to use a pharmacological agent, sertraline, to increase neural cell differentiation and their survival. Purified endometrial stem cells (EnSCs) were examined for neuronal and glial cell specific markers after retinoic acid (RA) and sertraline treatment via RT-PCR, immunocytochemistry and Western blot analysis. The survival of differentiated cells was measured by MTT assay and the frequency of apoptosis, demonstrated by caspase-3-like activity. EnSCs were differentiated into neuronal cells after RA induction. Sertraline increased neuronal cell differentiation by 1.2-fold and their survival by 1.4-fold, and decreased from glial cell differentiation significantly. The findings indicate that sertraline could be used to improve the in vitro differentiation process of stem cells into neuronal cells, and may be involved in regenerative pharmacology in future.

Effects of crocin on inflammatory biomarkers and mental health status in patients with multiple sclerosis: A randomized, double-blinded clinical trial.

BACKGROUND: Multiple sclerosis (MS), as a demyelinating disease correlated with inflammation and oxidative stress, affects the central nervous system and causes a wide range of complications, including psychiatric disorders. Considering the anti-inflammatory and antioxidant properties associated with the bioactive components of saffron, such as crocin (trans-crocetin bis(ß-d-gentiobiosyl) ester), and their potential impact on ameliorating psychiatric symptoms, our study aimed to investigate the effect of crocin on biomarkers of inflammation, oxidative stress, and mental health, e.g., depression and anxiety in individuals with MS. METHOD: Patients with MS were randomized into two groups, taking either 15 mg crocin tablets twice a day (n = 25; 30 mg/day) or placebo tablets (n = 25) for 8 weeks. The valid and reliable Beck depression and anxiety scale questionnaire was recorded, and fasting blood samples were collected to measure biomarkers, including high-sensitivity C-reactive protein (hs-CRP), malondialdehyde (MDA), and nitric oxide (NO) at baseline and week 8 following the intervention. RESULTS: The data analysis using ANCOVA showed that supplementation with crocin for 8 weeks significantly lowered hs-CRP levels (p-value= 0.01). In addition, within-group comparisons showed crocin significantly decreased anxiety (p-value= 0.01). However, crocin did not affect serum MDA and NO after 8 weeks of intervention. CONCLUSION: Our findings suggest that crocin may keep promise in attenuating inflammation, evidenced by reducing hs-CRP in patients with MS. However, supplementation for 8 weeks may not be sufficient to improve mental health, and future clinical studies with higher sample sizes and various doses and durations are recommended.

5α-reductase 1 regulates spinal cord testosterone after morphine administration.

The enzyme 5alpha-reductase 1 (5α-R(1)) that converts testosterone (T) to dihydrotestosterone (DHT) is present in many mammalian tissues including the spinal cord. It is established that morphine administration decreases spinal cord T levels, but the mechanism is still undetermined. Here, we investigated the link between T and the enzyme 5α-R(1) in the spinal cord after morphine administration. For spinal cord steroid extraction, all the animals were killed 30 min, 2 h (acute) and 14 days (chronic) after first drug injection by decapitation. The whole spinal cord was removed and kept frozen at -20°C until T and DHT extraction. The effects of acute and chronic morphine administration on 5α-R(1) expression in the adult male rat spinal cord were evaluated using RT-PCR. Spinal cord T and DHT levels were measured using radioimmunoassay before and after the morphine exposure. Morphine significantly reduced the T concentration after acute and chronic exposure in the spinal cord. In contrast, the 5α-R(1) expression and of course DHT levels increased the following chronic morphine administration. One important reason for the decreasing effect of morphine exposure on the spinal cord T level is due to an increase in the 5α-R(1) levels. We suggest that morphine plays a regulatory role in metabolism of neurosteroids, especially T in the spinal cord via 5α-R(1).

Effect of risperidone on morphine-induced conditioned place preference and dopamine receptor D2 gene expression in male rat hippocampus.

BACKGROUND: Previous studies suggest the possible effect of risperidone on brain reward system and D1 and D2 dopamine receptors' involvement in morphine-induced conditioned place preference (CPP). AIMS: The present study was designed to investigate the effect of risperidone as an atypical antipsychotic drug on morphine-induced CPP and D2-like dopamine receptor gene expression in rat. MATERIALS AND METHODS: An unbiased CPP paradigm was used to study the effect of risperidone. Intraperitoneal (i.p.) injection of risperidone (1, 2, and 4 mg/kg) was performed 30 min before the morphine (10 mg/kg, i.p.) injection and just after the rat was placed in the CPP box. The open field test was used to assay the locomotor activity of animal. The gene expression of D2 dopamine receptor in hippocampus was measured by real-time PCR technique. The hippocampi of rats were also used for histology evaluation. RESULTS: Morphine-produced (10 mg/kg) CPP and morphine-induced CPP were reversed only by the administration of a low dose of risperidone (1 mg/kg). Low dose of risperidone (1 mg/kg) showed no effect on locomotor activity but a higher dose of risperidone (2 and 4 mg/kg) decreased locomotor activity. Real-time PCR data analysis revealed that the gene expression of D2 dopamine receptor had significant difference between morphine and a 1 mg/kg dose of risperidone. Moreover, in histological evaluation, apoptosis was observed in the morphine group, whereas there was no evidence of apoptosis in the risperidone-treated groups. CONCLUSION: Our results suggest that risperidone (1 mg/kg) reverses the morphine-induced CPP and may reduce the rewarding properties of morphine. It is also demonstrated that risperidone decreases the expression of D2 receptor in rat hippocampus. Therefore, risperidone can be considered potential adjunct therapy in morphine dependence.