Pro-vegetarian dietary pattern and risk of breast cancer: a case-control study.

BACKGROUND: There are a few conflicting results from studies assessing the association between plant-based diets, particularly pro-vegetarian dietary pattern (PDP), and breast cancer (BC) incidence. Therefore, this study aimed to investigate the association between PDP and BC odds in the Iranian population. METHODS: This case-control study was conducted on 134 women with BC and 265 without cancer (control). Participants were selected from two referral hospitals in Tehran, Iran. Also, a validated food frequency questionnaire was used to collect food information. Logistic regression was used to assess the association between PDP and BC and the association between PDP and BC by menopausal status. RESULTS: It was observed that in two models of logistic regression, the chance of BC was lower in the second and last tertile (T) than in the first tertile of PDP (model 1-T2: odds ratio (OR) = 0.39; 95% confidence interval (CI): 0.23-0.67; P = 0.001, and T3: OR = 0.43; 95% CI: 0.26-0.73; P = 0.002-model 2: T2: OR = 0.42; 95% CI: 0.24-0.74; P = 0.003, and T3: OR = 0.49; 95% CI: 0.27-0.88; P = 0.017). Also, according to menopausal status, the odds of developing BC in post-menopausal women in the second and last tertile of PDP was significantly lower than the first tertile in both logistic regression models. CONCLUSIONS: The findings revealed that Iranian women who followed PDP had a lower chance of developing BC. Also, we found that a diet high in plant-based foods and low in animal products is beneficial for reducing BC odds, particularly for post-menopausal women.

Cilostazol pretreatment prevents PTSD-related anxiety behavior through reduction of hippocampal neuroinflammation.

Current pharmacological treatments against post-traumatic stress disorder (PTSD) lack adequate efficacy. As a result, intense research has focused on identifying other molecular pathways mediating the pathogenesis of this condition. One such pathway is neuroinflammation, which has demonstrated a role in PTSD pathogenesis by causing synaptic dysfunction, neuronal death, and functional impairment in the hippocampus. Phosphodiesterase (PDE) inhibitors (PDEIs) have emerged as promising therapeutic agents against neuroinflammation in other neurological conditions. Furthermore, PDEIs have shown some promise in animal models of PTSD. However, the current model of PTSD pathogenesis, which is based on dysregulated fear learning, implies that PDE inhibition in neurons should enhance the acquisition of fear memory from the traumatic event. As a result, we hypothesized that PDEIs may improve PTSD symptoms through inhibiting neuroinflammation rather than long-term potentiation-related mechanisms. To this end, we tested the therapeutic efficacy of cilostazol, a selective inhibitor of PDE3, on PTSD-related anxiety symptoms in the underwater trauma model of PTSD. PDE3 is expressed much more richly in microglia and astrocytes compared to neurons in the murine brain. Furthermore, we used hippocampal indolamine 2,3-dioxygenase 1 (IDO) expression and interleukin 1 beta (IL-1ß) concentration as indicators of neuroinflammation. We observed that cilostazol pretreatment prevented the development of anxiety symptoms and the increase in hippocampal IDO and IL-1ß following PTSD induction. As a result, PDE3 inhibition ameliorated the neuroinflammatory processes involved in the development of PTSD symptoms. Therefore, cilostazol and other PDEIs may be promising candidates for further investigation as pharmacological therapies against PTSD.

The Zebrafish Model as a New Discovery Path for Medicinal Plants in the Treatment of Parkinson's Disease.

Parkinson's disease (PD) is one of the most frequent degenerative central nervous system disorders affecting older adults. Dopaminergic neuron failure in the substantia nigra is a pathological sign connected with the motor shortfall of PD. Due to their low teratogenic and adverse effect potential, medicinal herbs have emerged as a promising therapy option for preventing and curing PD and other neurodegenerative disorders. However, the mechanism through which natural compounds provide neuroprotection against PD remains unknown. While testing compounds in vertebrates such as mice is prohibitively expensive and time-consuming, zebrafish (Danio rerio) may offer an appealing alternative because they are vertebrates and share many of the same characteristics as humans. Zebrafish are commonly used as animal models for studying many human diseases, and their molecular history and bioimaging properties are appropriate for the study of PD. However, a literature review indicated that only six plants, including Alpinia oxyhylla, Bacopa monnieri, Canavalia gladiate, Centella asiatica, Paeonia suffruticosa, and Stachytarpheta indica had been investigated as potential PD treatments using the zebrafish model. Only C. asiatica and B. monnieri were found to have potential anti-PD activity. In addition to reviewing the current state of research in this field, these plants' putative mechanisms of action against PD are explored, and accessible assays for investigation are made.

Finding Integrative Medication for Neuroblastoma and Glioblastoma through Zebrafish as A Model of Organism.

As far as malignant tumors of the central nervous system are concerned, glioblastoma (GB) and neuroblastoma (NB) are the most prevalent, aggressive, and fatal forms in adult and pediatric populations, respectively. NB is the most prominent childhood extracranial compact neoplasm in pediatrics when the embryo develops from undifferentiated neural crest cells. Regarding malignant primary brain tumors, GB is the most lethal and difficult to treat. Currently, there are few effective treatments available for either condition. Research using zebrafish is relatively new in the field of animal cancer studies, and the first results show promise. In particular, integrated genomic investigations of NB and GB have revealed the potential of the zebrafish model in elucidating the roles of specific genetic changes in the development of this fatal childhood malignancy. Hence, this study examines the possibility of zebrafish as a model organism for discovering integrative medicines for these types of cancer. This model is an excellent animal model for study due to its transparency, ease of genetic modification, ethics and financial benefits, and preservation of the primary brain areas andbloodbrain barrier (BBB). This review provides recent developments in the zebrafish model of NB and GB to illustrate the benefits of using them in cancer studies as a model of the organism. This approach provides novel insights into delivering individualized treatment and enhancing outcomes for people coping with central nervous system malignancies.

Process-related Factors Are as Important as Outcomes for Patients Undergoing Nonsurgical Root Canal Treatment, Nonsurgical Root Canal Retreatment, and Endodontic Microsurgery.

INTRODUCTION: There is considerable variation in the reporting of treatment outcomes in endodontics. Patient-centered outcomes are often inadequately reported in endodontic outcome studies. This paper explores patients' expectations and reported outcomes in nonsurgical root canal treatment (NS-RCT), nonsurgical root canal retreatment (NS-ReTx), and endodontic microsurgery (EMS). METHODS: We used a qualitative description approach and conducted telephone and virtual semi-structured interviews with participants who had the following treatments within the preceding 3-12 months: NS-RCT (n = 10), NS-ReTx (n = 10), or EMS (n = 10). Half of these treatments were performed by senior endodontic residents in an academic setting and the other half by a community-based endodontist at a private practice. RESULTS: Participants identified several outcomes that were important to them and integral to treatment success, such as tooth survival, resolution of symptoms, aesthetics, and radiographic healing. Process-related factors were as important as treatment outcomes for participants. Communicating with and educating patients during treatment increased participants' satisfaction and lowered their stress. Dissatisfaction was linked to the lack of a comprehensive treatment and follow-up plan. Thorough planning ensured that patients were fully informed and had a structured approach to achieving their desired outcomes. CONCLUSIONS: This study provides a list of outcomes that are important for patients undergoing NS-RCT, NS-ReTx, and EMS. These outcomes should be considered when developing a core outcome set related to endodontic treatments. Additionally, this study reports patients' expectations regarding process-related factors that are essential for providing patient-centered care and improving patient experience.

Phosphodiesterase inhibitors in psychiatric disorders.

RATIONALE: Challenges in drug development for psychiatric disorders have left much room for the introduction of novel treatments with better therapeutic efficacies and indices. As a result, intense research has focused on identifying new targets for developing such pharmacotherapies. One of these targets may be the phosphodiesterase (PDE) class of enzymes, which play important roles in intracellular signaling. Due to their critical roles in cellular pathways, these enzymes affect diverse neurobiological functions from learning and memory formation to neuroinflammation. OBJECTIVES: In this paper, we reviewed studies on the use of PDE inhibitors (PDEIs) in preclinical models and clinical trials of psychiatric disorders including depression, anxiety, schizophrenia, post-traumatic stress disorder (PTSD), bipolar disorder (BP), sexual dysfunction, and feeding disorders. RESULTS: PDEIs are able to improve symptoms of psychiatric disorders in preclinical models through activating the cAMP-PKA-CREB and cGMP-PKG pathways, attenuating neuroinflammation and oxidative stress, and stimulating neural plasticity. The most promising therapeutic candidates to emerge from these preclinical studies are PDE2 and PDE4 inhibitors for depression and anxiety and PDE1 and PDE10 inhibitors for schizophrenia. Furthermore, PDE3 and 4 inhibitors have shown promising results in clinical trials in patients with depression and schizophrenia. CONCLUSIONS: Larger and better designed clinical studies of PDEIs in schizophrenia, depression, and anxiety are warranted to facilitate their translation into the clinic. Regarding the other conditions discussed in this review (most notably PTSD and BP), better characterization of the effects of PDEIs in preclinical models is required before clinical studies.

Zebrafish, a biological model for pharmaceutical research for the management of anxiety.

The zebrafish (Danio rerio) is a valuable animal model rapidly becoming more commonly used in pharmaceutical studies. Due to its low-cost maintenance and high breeding potential, the zebrafish is a suitable substitute for most adult rodents (mice and rats) in neuroscience research. It is widely used in various anxiety models. This species has been used to develop a conceptual framework for anxiety behavior studies with broad applications in the laboratory, including the study of herbal and chemical drugs. This review discusses the latest studies of anxiety-related behavior in the zebrafish model.

Neuronal nitric oxide synthase inhibition accelerated the removal of fluoxetine's anxiogenic activity in an animal model of PTSD.

While SSRIs are the current first-line pharmacotherapies against post-traumatic stress disorder (PTSD), they suffer from delayed onset of efficacy and low remission rates. One solution is to combine SSRIs with other treatments. Neuronal nitric oxide synthase (nNOS) has been shown to play a role in serotonergic signaling, and there is evidence of synergism between nNOS modulation and SSRIs in models of other psychiatric conditions. Therefore, in this study, we combined subchronic fluoxetine (Flx) with 7-nitroindazole (NI), a selective nNOS inhibitor, and evaluated their efficacy against anxiety-related behavior in an animal model of PTSD. We used the underwater trauma model to induce PTSD in rats. Animals underwent the open field (OFT) and elevated plus maze tests on days 14 (baseline) and 21 (post-treatment) after PTSD induction to assess anxiety-related behaviors. Between the two tests, the rats received daily intraperitoneal injections of 10 mg/kg Flx or saline, and were injected intraperitoneally before the second test with either 15 mg/kg NI or saline. The change in behaviors between the two tests was compared between treatment groups. Individual treatment with both Flx and NI had anxiogenic effects in the OFT. These effects were associated with modest increases in cFOS expression in the hippocampus. Combination therapy with Flx + NI did not show any anxiogenic effects, while causing even higher expression levels of cFOS. In conclusion, addition of NI treatment to subchronic Flx therapy accelerated the abrogation of Flx's anxiogenic properties. Furthermore, hippocampal activity, as evidenced by cFOS expression, was biphasically related to anxiety-related behavior.

Targeting neuronal nitric oxide synthase and the nitrergic system in post-traumatic stress disorder.

RATIONALE: Current pharmacological approaches to treatment of post-traumatic stress disorder (PTSD) lack adequate effectiveness. As a result, identifying new molecular targets for drug development is necessary. Furthermore, fear learning and memory in PTSD can undergo different phases, such as fear acquisition, consolidation, and extinction. Each phase may involve different cellular pathways and brain regions. As a result, effective management of PTSD requires mindfulness of the timing of drug administration. One of the molecular targets currently under intense investigation is the N-methyl-D-aspartate (NMDA)-type glutamate receptor (NMDAR). However, despite the therapeutic efficacy of drugs targeting NMDAR, their translation into clinical use has been challenging due to their various side effects. One possible solution to this problem is to target signaling proteins downstream to NMDAR to improve targeting specificity. One of these proteins is the neuronal nitric oxide synthase (nNOS), which is activated following calcium influx through the NMDAR. OBJECTIVE: In this paper, we review the literature on the pharmacological modulation of nNOS in animal models of PTSD to evaluate its therapeutic potential. Furthermore, we attempt to decipher the inconsistencies observed between the findings of these studies based on the specific phase of fear learning which they had targeted. RESULTS: Inhibition of nNOS may inhibit fear acquisition and recall, while not having a significant effect on fear consolidation and extinction. However, it may improve extinction consolidation or reconsolidation blockade. CONCLUSIONS: Modulation of nNOS has therapeutic potential against PTSD and warrants further development for use in the clinical setting.

Dose-dependent effect of carbohydrate restriction for type 2 diabetes management: a systematic review and dose-response meta-analysis of randomized controlled trials.

BACKGROUND: Carbohydrate restriction is effective for type 2 diabetes management. OBJECTIVES: We aimed to evaluate the dose-dependent effect of carbohydrate restriction in patients with type 2 diabetes. METHODS: We systematically searched PubMed, Scopus, and Web of Science to May 2021 for randomized controlled trials evaluating the effect of a carbohydrate-restricted diet (≤45% total calories) in patients with type 2 diabetes. The primary outcome was glycated hemoglobin (HbA1c). Secondary outcomes included fasting plasma glucose (FPG); body weight; serum total, LDL, and HDL cholesterol; triglyceride (TG); and systolic blood pressure (SBP). We performed random-effects dose-response meta-analyses to estimate mean differences (MDs) for a 10% decrease in carbohydrate intake. RESULTS: Fifty trials with 4291 patients were identified. At 6 months, compared with a carbohydrate intake between 55%-65% and through a maximum reduction down to 10%, each 10% reduction in carbohydrate intake reduced HbA1c (MD, -0.20%; 95% CI, -0.27% to -0.13%), FPG (MD, -0.34 mmol/L; 95% CI, -0.56 to -0.12 mmol/L), and body weight (MD, -1.44 kg; 95% CI, -1.82 to -1.06 kg). There were also reductions in total cholesterol, LDL cholesterol, TG, and SBP. Levels of HbA1c, FPG, body weight, TG, and SBP decreased linearly with the decrease in carbohydrate intake from 65% to 10%. A U-shaped effect was seen for total cholesterol and LDL cholesterol, with the greatest reduction at 40%. At 12 months, a linear reduction was seen for HbA1c and TG. A U-shaped effect was seen for body weight, with the greatest reduction at 35%. CONCLUSIONS: Carbohydrate restriction can exert a significant and important reduction on levels of cardiometabolic risk factors in patients with type 2 diabetes. Levels of most cardiometabolic outcomes decreased linearly with the decrease in carbohydrate intake. U-shaped effects were seen for total cholesterol and LDL cholesterol at 6 months and for body weight at 12 months.

No association between dietary magnesium intake and body composition among Iranian adults: a cross-sectional study.

PURPOSE: Obesity is becoming more prevalent worldwide. Magnesium (Mg) intake may play a role in the regulation of energy metabolism and body weight. Therefore, in this cross-sectional study, we aimed to investigate the association between dietary Mg intake and body composition among healthy adults. METHODS: A total of 778 adult men and women aged 18-59 years who attended health care centers in Tehran, Iran, entered the final analysis. Dietary intake was assessed with a validated and reliable food frequency questionnaire with 168 items and the dietary Mg intake was estimated using Nutritionist IV software. Anthropometric measurements and blood samples were collected and body composition was evaluated employing the Body Mass Index (BMI), A Body Shape Index (ABSI), Body Adiposity Index (BAI), Body Roundness Index (BRI), Visceral Adiposity Index (VAI), Lipid Accumulation Index (LAP), and Triglyceride-Glucose index (TyG). Multiple linear regression analysis was used to determine the association of the dietary Mg intake with body composition indices. RESULTS: The mean daily dietary Mg intake was 294 ± 140 mg in men and 262 ± 112 mg in women. Unadjusted linear regression showed that dietary magnesium intake is significantly associated with a waist to hip ratio (WHR) and total cholesterol (TC) in men, and hip circumference (HC) in women. After adjusting for potential confounders including age, education, marriage, occupation and smoking, total energy intake, and activity score, there remained no significant association between dietary Mg intake and any of the body composition indices including BMI, ABSI, BAI, BRI, VAI, LAP, and TyG neither in men nor women. CONCLUSION: Higher Mg intake was not associated with anthropometric indices in Iranian adults, according to our findings. Additional observational studies would be beneficial in clarifying the existing findings.