Is oral consumption of dates (Phoenix dactylifera L. fruit) in the peripartum period effective and safe integrative care to facilitate childbirth and improve perinatal outcomes: a comprehensive revised systematic review and dose-response meta-analysis.

BACKGROUND: Recent reviews have reported inconclusive results regarding the usefulness of consuming dates (Phoenix dactylifera L. fruit) in the peripartum period. Hence, this updated systematic review with meta-analysis sought to investigate the efficacy and safety of this integrated intervention in facilitating childbirth and improving perinatal outcomes. METHODS: Eight data sources were searched comprehensively from their inception until April 30, 2023. Parallel-group randomized and non-randomized controlled trials published in any language were included if conducted during peripartum (i.e., third trimester of pregnancy, late pregnancy, labor, or postpartum) to assess standard care plus oral consumption of dates versus standard care alone or combined with other alternative interventions. The Cochrane Collaboration's Risk of Bias (RoB) assessment tools and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) were employed to evaluate the potential RoB and the overall quality of the evidence, respectively. Sufficient data were pooled by a random-effect approach utilizing Stata software. RESULTS: Of 2,460 records in the initial search, 48 studies reported in 55 publications were included. Data were insufficient for meta-analysis regarding fetal, neonatal, or infant outcomes; nonetheless, most outcomes were not substantially different between dates consumer and standard care groups. However, meta-analyses revealed that dates consumption in late pregnancy significantly shortened the length of gestation and labor, except for the second labor stage; declined the need for labor induction; accelerated spontaneity of delivery; raised cervical dilatation (CD) upon admission, Bishop score, and frequency of spontaneous vaginal delivery. The dates intake in labor also significantly reduced labor duration, except for the third labor stage, and increased CD two hours post-intervention. Moreover, the intervention during postpartum significantly boosted the breast milk quantity and reduced post-delivery hemorrhage. Likewise, dates supplementation in the third trimester of pregnancy significantly increased maternal hemoglobin levels. The overall evidence quality was also unacceptable, and RoB was high in most studies. Furthermore, the intervention's safety was recorded only in four trials. CONCLUSION: More well-designed investigations are required to robustly support consuming dates during peripartum as effective and safe integrated care. TRIAL REGISTRATION: PROSPERO Registration No: CRD42023399626.

Sublingual prophylactic administration of OVA-loaded MSC-derived exosomes to prevent allergic sensitization.

AIM: This study evaluated the immunomodulatory and delivery potential of adipose tissue-isolated MSC-derived exosomes as a prophylactic regimen through a sublingual route in the ovalbumin (OVA)-induced allergic asthma murine model. MATERIAL AND METHODS: Balb/c mice received 10 µg/dose of OVA-enriched MSC-derived exosomes as a prophylactic regimen in six doses during three weeks, and then OVA sensitization was conducted through intraperitoneal and aerosol administration of allergen. The total cells and eosinophils counted in nasal lavage fluid (NALF) and lung tissues were assessed for histopathological analysis. In addition, the secretion of IFN-γ, IL-4, and TGF-ß by spleen cells and serum OVA-specific IgE levels were measured via ELISA. RESULTS: Significant reduction in the IgE levels and IL-4 production, along with elevated TGF-ß levels, were observed. Also, limited cellular infiltrations and perivascular and peribronchiolar inflammation in the lung tissues and normal total numbers of cells and eosinophils in the NALF were reported. CONCLUSION: Prophylactic regimen using OVA-enriched MSC-derived exosomes modulated immune responses and inhibited allergic OVA sensitization.

Allergen specific immunotherapy with plasmid DNA encoding OVA-immunodominant T cell epitope fused to Tregitope in a murine model of allergy.

BACKGROUND: Peptide-based immunotherapy (PIT) was introduced as an attractive approach in allergen-specific immunotherapy (AIT). However, PIT clinical trials have shown variable results, and immune response to peptides is not precisely predictable. On the other hand, induction of antigen-specific tolerance may be augmented when allergens are combined with the regulatory T cell epitope (Tregitope). This study aimed to evaluate the therapeutic administration of a plasmid DNA encoding Tregitope and ovalbumin (OVA) immunodominant epitope in the murine model of allergy. METHODS: Following the induction of allergic rhinitis by ovalbumin, vaccinated group received three doses of recombinant plasmid containing Signal peptide-Tregitope-OVA T cell epitope. After the final OVA challenge, clinical symptoms, histopathological changes, OVA-specific IgE level, and cytokine secretion pattern of spleen cells were examined. RESULTS: Our data are showing that AIT with the recombinant DNA vaccine significantly suppressed airway inflammation; reduced eosinophilic infiltration in the nasal mucosa; decreased expression level of IL-4 and IL-17 in spleen cells, while IFN-γ, IL-10, and TGF-ß expression were increased. Moreover, OVA-specific IgE levels were also decreased. CONCLUSION: These results suggest that Tregitope-immunodominant T cell epitope fusion can act as a safe and effective approach in DNA-based allergen-specific immunotherapy.

Effect of water-soluble PM10 on the production of TNF-α by human monocytes and induction of apoptosis in A549 human lung epithelial cells.

Long-term exposure to airborne particles of 10 µm and less in size (PM10) in dust can lead to increased risk of diseases such as respiratory, cardiovascular, lung cancer and atherosclerosis. The aim of the study was to evaluate the effects of water-soluble PM10 particles in the Middle East Dust (MED) storm in Ahvaz, Iran, on the production of TNF-α by human monocytes. In addition, we assessed the level of induction of apoptosis in isolated A549 human pulmonary epithelial cells. For this purpose, isolated human blood monocytes (250,000 to 300,000 cell/ ml) as well as isolated human pulmonary A549 epithelial cells (100,0000 cell/ ml) were exposed to various concentrations (62.5, 125, 250, 500 µg/ml) of water-soluble PM10 particles for different incubation periods (12, 24, 48 h). The results showed that exposure to PM10 particles increased the production of TNF-α in human monocytes and promoted apoptosis induction in A549 cells, in both concentration and incubation of period-dependent manner. In conclusion, airborne dust particles in Ahvaz city contain active compounds capable of increasing production of the pro-inflammatory cytokine, TNF-α, and inducing apoptosis of lung epithelial cells.

Neuroprotective Effects of Chrysin Mediated by Estrogenic Receptors Following Cerebral Ischemia and Reperfusion in Male Rats.

INTRODUCTION: Ischemic stroke is one of the leading causes of morbidity and mortality worldwide. Neuroprotective strategies were reported to attenuate cognitive deficits after ischemic incidents. Here we studied the neuroprotective potential of chrysin in a rat model of cerebral Ischemia/Reperfusion (I/R) in the presence or absence of Estrogen Receptors (ERs). METHODS: Adult male Wistar rats were pretreated with chrysin (CH) (CH; 30 mg/kg; gavage; for 21 consecutive days) alone or with selective ERs antagonists (ERα antagonist MPP; ERß antagonist PHTPP; IP) or nonselective ERs antagonist (ICI182780; IP). Then, the bilateral common carotid arteries were occluded for 20 min, which was followed by 72 h reperfusion. Subsequently, cognitive performance was evaluated by Morris Water Maze (MWM) and shuttle box tasks, and afterward, their hippocampi were removed for ELISA assays and H&E staining. Oxidative indicators Malondialdehyde (MDA) and Glutathione Peroxidase (GPx), as well as inflammation mediators interleukin (IL)-1ß and tumor necrosis factor-alpha (TNFα), were measured using commercial kits. RESULTS: Results of the current study showed that the anti-oxidative and anti-inflammatory properties of CH are possible mechanisms that could improve cognitive deficits and prevent neuronal cell death following I/R (P<0.001). These effects were reversed by ICI182780 (P>0.05). Furthermore, when chrysin was co-treated with ERß antagonist, PHTPP showed a weak neuroprotective effect in I/R rats. However, these parameters were not significantly different when chrysin was combined with ERα antagonist MPP. CONCLUSION: Our data confirm that chrysin could potentially serve as a neuroprotective agent against devastating effects of cerebral I/R injury, which may be mediated via its interaction with ERs, especially ERß.

Therapeutic effects of Wharton's jelly-derived Mesenchymal Stromal Cells on behaviors, EEG changes and NGF-1 in rat model of the Parkinson's disease.

Human Wharton's jelly-derived Mesenchymal Stromal Cells (hWJ-MSCs) have shown beneficial effects in improving the dopaminergic cells in the Parkinson's disease (PD). In the present study, the effects of hWJ-MSCs on hyperalgesia, anxiety deficiency and Pallidal local electroencephalogram (EEG) impairment, alone and combined with L-dopa, were examined in a rat model of PD. Adult male Wistar rats were divided into five groups: 1) sham, 2) PD, 3) PD + C (Cell therapy), 4) PD + C+D (Drug), and 5) PD + D. PD was induced by injection of 6-OHDA (16 µg/2 µl into medial forebrain bundle (MFB)). PD + C group received hWJ-MSCs (1 × 106 cells, intravenous (i.v.)) twice post PD induction. PD + C+D groups received hWJ-MSCs combined with L-Dopa/Carbidopa, (10/30 mg/kg, intraperitoneally (i.p.)). PD + D group received L-Dopa/Carbidopa alone. Four months later, analgesia, anxiety-like behaviors, were evaluated and Pallidal local EEG was recorded. Level of insulin-like growth factor 1 (IGF-1) was measured in the striatum and dopaminergic neurons were counted in substantia nigra (SNc). According to data, MFB-lesioned rats showed hyperalgesia in tail flick, anxiety-like symptoms in cognitive tests, impairment of electrical power of pallidal local EEG as field potential, count of dopaminergic neurons in SNc and level of IGF-1 in striatum. These complications restored significantly by MSCs treatment (p < 0.001). Our findings confirm that chronic treatment with hWJ-MSC, alone and in combination with L-Dopa, improved nociception and cognitive deficit in PD rats which may be the result of increasing IGF-1 and protect the viability of dopaminergic neurons.

Neuroprotective effects of Wharton's jelly-derived mesenchymal stem cells on motor deficits due to Parkinson's disease.

OBJECTIVES: Human Wharton's jelly-derived mesenchymal stem cells (hWJ-MSCs) have been recognized as a potential tool to replace damaged cells by improving the survival of the dopaminergic cells in Parkinson's disease (PD). In this study, we examined the effects of hWJ-MSCs and associated with L-dopa/carbidopa on motor disturbances in the PD model. MATERIALS AND METHODS: PD was induced by injection of 6-hydroxydopamine (6-OHDA) (16 µg/2 µl into medial forebrain bundle (MFB)). Sham group received a vehicle instead of 6-OHDA. PD+C group received hWJ-MSCs twice on the 14th and 28th days post PD induction. PD+C+D group received hWJ-MSCs and also L-dopa/carbidopa (10/30 mg/kg). PD+D group received L-dopa/carbidopa alone. Four months later, motor activities (the parameters of locomotor and muscle stiffness) were evaluated, dopaminergic neurons were counted in substantia nigra pars compacta (SNc), the level of dopamine (DA), and tyrosine hydroxylase (TH) were measured in the striatum. RESULTS: Data indicated that motor activities, the number of dopaminergic neurons, and levels of DA and TH activities were significantly reduced in PD rats as compared to the sham group (P<0.001). However, the same parameters were improved in the treated groups when compared with the PD group (P<0.001 and P<0.01, respectively). CONCLUSION: The chronic treatment of PD rats with hWJ-MSCs and L-dopa/carbidopa, improved motor activity, which may be the result of increased TH activity and due to released DA from dopaminergic neurons.

Chemo/radiotherapy-Induced Bone Marrow Niche Alterations.

Bone marrow (BM) niche is a specific microenvironment for hematopoietic stem cells (HSCs) as well as non-hematopoietic cells. Evidence shows that chemo/radiotherapy can lead to the disruption of different properties of HSCs such as proliferation, differentiation, localization, self-renewa, and steady-state of cell populations. Investigations have shown that the deregulation of balance within the marrow cavity due to chemo/radiotherapy could lead to bone loss, abnormal hematopoiesis, and enhanced differentiation potential of mesenchymal stem cells towards the adipogenic lineage. Therefore, understanding the underlying mechanisms of chemo/radiotherapy induced BM niche changes may lead to the application of appropriate therapeutic agents to prevent BM niche defects. Highlights Chemo/radiotherapy disrupts the steady-state of bone marrow niche cells and result in deregulation of normal balance of stromal cell populations. Chemo/radiotherapy agents play a significant role in reducing of bone formation as well as fat accumulation in the bone marrow niche. Targeting molecular pathways may lead to recovery of bone marrow niches after chemo/radiotherapy.

Transplanted Wharton's jelly mesenchymal stem cells improve memory and brain hippocampal electrophysiology in rat model of Parkinson's disease.

BACKGROUND: Experimental findings have shown that stem cell transplantation is a therapeutic procedure for Parkinson's disease (PD). In this study, effects of human Wharton's jelly-derived mesenchymal stem cells (hWJ-MSCs), alone and combined with l-dopa, were examined for repairing memory impairment in a rat model of PD. METHODS: Fifty adult male Wistar rats were randomly divided into five groups: 1) sham, 2) PD, 3) PD + C, 4) PD + C+D, and 5) PD + D. PD was induced by 6-OHDA injection (16 µg/2 µl) into medial forebrain bundle (MFB) and was confirmed 14 days later by contralateral rotation using apomorphine injection. The rats received hWJ-MSCs (1 × 106 cells, i.v.) twice on the 14th and 28th days post PD induction. Treated PD rats received hWJ-MSCs alone or combined with l-Dopa and Carbidopa (10/30 mg/kg, i.p.). Four months later, memory, hippocampal long-term potentiation (hLTP), histological changes, and the levels of BDNF and NGF in striatum were evaluated. RESULTS: PD caused both cell loss with small dark stained nuclei in granular zone as well as significant decrement of BDNF and NGF (P < 0.001) in striatum. These pathological alterations were associated with memory and hLTP deficits (P < 0.001 respectively). Treating PD rats with hWJ-MSCs, alone (P < 0.05 and P < 0.001) and combined with l-Dopa (P < 0.001), significantly restored the levels of both of the neurotrophins followed by improving cognition and hLTP (P < 0.001). CONCLUSION: Current findings showed that chronic treatment of PD rats with hWJ-MSCs, alone and in combination with l-Dopa, could restore memory and hLTP by reconstructing dopaminergic neurons and elevating the BDNF and NGF factors.

Protective effects of Chrysin against memory impairment, cerebral hyperemia and oxidative stress after cerebral hypoperfusion and reperfusion in rats.

Stroke is devastating and a leading cause of morbidity and mortality worldwide. Cerebral ischemia-reperfusion and its subsequent reactive hyperemia lead to neuronal damage in the hippocampus and cognitive decline. Chrysin (5, 7-dihydroxyflavone) is a well-known member of the flavonoid family with antioxidant and neuroprotective effects. Therefore, in the present study, the aim was to investigate whether chrysin will be able to recover the brain function caused by ischemia-reperfusion (I/R) in rats. Adult male Wistar rats (250-300 g) were randomly divided into five groups: and submitted to cerebral I/R or a sham surgery after three-weeks of pretreatment with chrysin (CH; 10, 30 and 100 mg/kg; P.O.) and/or normal saline containing %5 DMSO. Subsequently, sensorimotor scores, cognition, local cerebral blood flow, extracellular single unit, and histological parameters were evaluated following I/R. Hippocampus was used to evaluate biomarkers including: oxidative stress parameters and prostaglandin E2 (PGE2) using ELISA kits. Data showed that pretreatment with chrysin significantly improved sensorimotor signs, passive avoidance memory, and attenuated reactive hyperemia, and increased the average number of spikes/bin (p < 0.001). Furthermore, chrysin pre-treatment significantly decreased the levels of MDA, NO, and PGE2 (p < 0. 001), while increased the levels of GPX and the number of surviving cells in the hippocampal CA1 region (p < 0.01, p < 0.001; respectively). This study demonstrates that chrysin may have beneficial effects in the treatment of cognitive impairment and help recover the brain dysfunction induced by I/R.

An evaluation of the effect of saffron supplementation on the antibody titer to heat-shock protein (HSP) 70, hsCRP and spirometry test in patients with mild and moderate persistent allergic asthma: A triple-blind, randomized placebo-controlled trial.

BACKGROUND: Asthma is a heterogeneous disease, which usually associated with chronic airway inflammation. The anti-heat shock protein (anti-HSP) 70 is a novel risk factor for asthma. The aim of the present study was to survey the effect of saffron supplementation on anti-HSP70, high-sensitivity C-reactive protein (hs-CRP) and spirometry test in patients with allergic asthma. BASIC PROCEDURES: In this clinical trial, patients (N = 80, 32 women and 48 men, 18-65 years old) with mild and moderate allergic asthma were randomized into two groups: a group of patients who received two capsules of saffron (100 mg/d) and a control group who received two capsules of placebo for 8 weeks. Anti-HSP70, hs-CRP and spirometry test were determined in patients before (week 0) and after (week 8) intervention. SPSS software (version 16.0; Inc, Chicago, IL) was used for data analysis. MAIN FINDINGS: Saffron in comparison with placebo significantly reduced the hs-CRP (p < 0.001) and anti-HSP70 (p < 0.001) concentrations. In spirometry test, forced expiratory volume in first second(FEV1), forced vital capacity (FVC), FEV1/FVC ratio and forced expiratory flow 25-75%.(FEF 25-75) increased significantly in saffron in comparison to placebo group (p < 0.05). PRINCIPAL CONCLUSIONS: Results of the present study suggested that saffron supplementation in patients with allergic asthma decreased significantly anti-HSPs 70 and hs-CRP and also improved some spirometry test factors.

The protective effect of betulinic acid on microvascular responsivity and protein expression in alzheimer disease induced by cerebral micro-injection of beta-amyloid and streptozotocin.

OBJECTIVE: Alzheimer's disease (AD) is mainly caused by accumulation of ß-amyloid (Aß) in vessels or parenchyma of the brain. Accordingly, natural compounds such as betulinic acid (BA) might improve the AD signs by increase in blood flow and through reduction in amyloid plaques. METHODS: Intra-hippocampal injection of BA (0.2 and 0.4 µmol/L /10 µL DMSO /rat) was done at intervals of 180 and 10 min before co-microinjection of 0.1 µmol/L Aß dissolved in PBS (5 µL/rat, hippocampi) and 1.5 mg/kg Streptozotocin dissolved in aCSF (10 µL/rat, lateral ventricles). Cerebro-vascular responsivity tested by Laser Doppler, BBB leakage, Elisa assays of cytokines (TNF-α and IL-10), and Western blot analysis of proteins (BDNF and AchE) in the hippocampus were assessed 1 month after the injections. RESULTS: Microvascular reaction and BBB function were significantly impaired in AD rats, which were improved via BA pretreatment. BA could increase BDNF expression and decrease cytokine levels in the hippocampus of AD rats (especially 0.1 µmol/L Aß: 0.4 µmol/L BA); however, no significant changes were detected in the blotting of AchE among the groups. CONCLUSIONS: Betulinic acid could have a role in AD through protecting microcirculation, alleviating inflammation, and up-regulating BDNF expression which is clearer toward 1:4 molar ratios of Aß to BA.