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Allelopathic effects of Chenopodium album L. leaf aqueous extract on nitrification were investigated. In the presence of leaf extracts, complete nitrite oxidation to nitrate was delayed significantly. Also, in the presence of leaf extract the amounts of both nitrite and nitrate produced were significantly higher than those in control solutions. This increase was attributed to protein hydrolysis and ammonification of resulting amino acids present in leaf extracts. The delay in nitrification was proposed to be due to the presence of phenolic acids in this plant. [ABSTRACT FROM AUTHOR]

Background: Neuroblastoma (NB) is the most common extracranial solid tumor in pediatric. In highrisk NB patients, the 5-year overall survival rate (OS) remains a stark < 50 % with conventional therapies. Autologous hematopoietic stem cell transplantation with high dose chemotherapies was used in poor prognosis and high-risk patients.Today, Plerixafor is used to increase stem cells mobilization in patients who are candidates for autologous transplantation., Objective: This study examined safety and efficacy Plerixafor is administered as a subcutaneous injection in pediatric NB patients for stem cell mobilization STUDY DESIGN: A cohort of 19 pediatric neuroblastoma (NB) patients underwent autologous hematopoietic stem cell transplantation (HSCT) between February 2017 and April 2019, receiving G-CSF mobilization only. Subsequently, 37 NB patients underwent HSCT between December 2019 and October 2023, receiving both G-CSF and plerixafor for mobilization (auto-HSCT)., Results: The final product CD34 cell dose /kg was evidently higher in combination group at 5.363 ± 4.243 vs. G-CSF group at 2.827 ± 3.586 × 106(P value= 0.001). Neutrophils and platelet engraftment were occurred sooner in combination group compared with G-CSF group. The 1-year overall survival (OS) rate for the G-CSF and G-CSF-and-plerixafor combination group was 70.8 % and 63.3 %, respectively (P = 0.874). No statistically significant difference in OS or disease-free survival (DFS) was observed between the two treatment groups., Conclusion: The results show that plerixafor may be safe and effective in NB pediatric patients in routine clinical practice. It was well tolerated in NB patients and no specific side effects were observed. It was not associated with improved survival., (Copyright © 2025. Published by Elsevier Ltd.)

Gene therapy (GT) as a groundbreaking approach holds promise for treating many diseases including immune deficiencies and blood disorders. GT can benefit patients suffering from these diseases, especially those without matched donors or who are at risk after hematopoietic stem cell transplantation (HSCT). Due to all the advances in the field of GT, its main challenge is still gene delivery. Generally, gene delivery systems are categorized into two types depending on utilized vectors: non-viral and viral. Viral vectors are commonly used in GT because of their high efficiency compared to non-viral vectors. In this article, all clinical trials on viral-based GT (with the exclusion of CRISPR and CAR-T cell Therapy) in the last decade for immune deficiencies and blood disorders including Severe combined immune deficiency (SCID), Wiskott-Aldrich syndrome (WAS), Chronic granulomatous disease (CGD), Leukocyte adhesion deficiency (LAD), Fanconi anemia (FA), Hemoglobinopathies, and Hemophilia will thoroughly be discussed. Moreover, viral vectors used in these trials including Retroviruses (RVs), Lentiviruses (LVs), and Adeno-Associated Viruses (AAVs) will be reviewed. This review provides a concise overview of traditional treatments for the mentioned disease and precise details of their viral-based GT clinical trial studies in the last decade, then presents the advantages, disadvantages, and potential adverse events of GT. In conclusion, this review presents GT as a hopeful and growing field in healthcare that could offer cures to diseases that were previously thought to be untreatable., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Background: Global longitudinal strain (GLS) has been used to identify patients at risk for cancer-therapy related cardiac dysfunction (CTRCD). However, there is limited data on the effectiveness of initiating cardioprotective therapy based on a strain-guided strategy in early stage HER2+ breast cancer patients. This randomized clinical trial assessed if treatment with carvedilol based on a strain-guided strategy can prevent development of CTRCD in HER2+ breast cancer patients on non-anthracycline based regimens., Methods: Study participants were prospectively assigned to one of four arms. Patients with normal LVEF and GLS remained in Arm A. Patients whose GLS decreased by > 15% from baseline or to < -15% during follow up were randomized 1:1 to prophylactic carvedilol (Arm B) or no therapy (Arm C). Patients who developed CTRCD were assigned to Arm D. The primary endpoint was GLS stability. The secondary endpoints were development of CTRCD and rate of anti-HER2 treatment interruption., Results: Among 110 patients who completed follow up, 84 were assigned to Arm A, 10 each were randomized to Arms B or C, and 6 were assigned to Arm D. At the end of the study period, there were no significant differences in GLS stability, development of CTRCD, or number of cancer therapy cycles completed between patients who did and did not receive cardioprotective therapy., Conclusions: In this prospective randomized GLS-guided study of prophylactic carvedilol in early stage HER2+ breast cancer patients on non-anthracycline regimens, there were no significant difference between groups in GLS stability, CTRCD or trastuzumab cycles held. These findings may identify a low-risk group of patients who may be considered for less intensive cardiac surveillance., Trial Registration: https://clinicaltrials.gov/study/NCT02993198 . Start date: 4/2015. This trial included patients who were retrospectively registered., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the Northwestern University Institutional Review Board. Consent for publication: Not applicable. Competing interests: SR is a consultant for Abbott Laboratories. GM is a full-time employee and shareholder of Abbott Laboratories. NA received research funding from Abbott Laboratories. The other authors declare no conflict of interest., (© 2024. The Author(s).)

Competing Interests: Conflicts of interest The authors declare no conflict of interest.

Background: Epidemiological data regarding the prevalence of bacterial multidrug-resistant (MDR) Gram-negative infections in patients with COVID-19 in Iran are still ambiguous. Thus, in this study we have investigated the epidemiology, risk factors for death, and clinical outcomes of bacterial infections among patients with COVID-19 in the intensive care unit (ICU)., Method: This retrospective cohort study included patients with COVID-19 hospitalized in the ICU of a university hospital in Iran between June 2021 and December 2021. We evaluated the epidemiological, clinical, and microbiological features, outcomes and risk factors associated with death among all COVID-19 patients. Data and outcomes of these patients with or without bacterial infections were compared. Kaplan-Meier plot was used for survival analyses., Results: In total, 505 COVID-19 patients were included. The mean age of the patients was 52.7 ± 17.6 years and 289 (57.2%) were female. The prevalence of bacterial infections among hospitalized patients was 14.9%, most of them being hospital-acquired superinfections (13.3%). MDR Klebsiella pneumoniae and Staphylococcus aureus were the most common pathogens causing respiratory infections. Urinary tract infections were most frequently caused by MDR Escherichia coli and K. pneumoniae . The overall in-hospital mortality rate of COVID-19 patients was 46.9% (237/505), while 78.7% (59/75) of patients with bacterial infections died. Infection was significantly associated with death (OR 6.01, 95% CI = 3.03-11.92, p -value <0.0001) and a longer hospital stay ( p  < 0.0001). Multivariate logistic regression analysis showed that Age (OR = 1.04, 95% CI = 1.03-1.06, p -value <0.0001), Sex male (OR = 1.70, 95% CI = 1.08-2.70, p -value <0.0001), Spo2 (OR = 1.99, 95% CI = 1.18-3.38, p -value = 0.010) and Ferritin (OR = 2.33, 95% CI = 1.37-3.97, p -value = 0.002) were independent risk factors associated with in-hospital mortality. Furthermore, 95.3% (221/232) of patients who were intubated died., Conclusion: Our findings demonstrate that bacterial infection due to MDR Gram-negative bacteria associated with COVID-19 has an expressive impact on increasing the case mortality rate, reinforcing the importance of the need for surveillance and strict infection control rules to limit the expansion of almost untreatable microorganisms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Akbari, Dehghani, Shirzadi, Pourajam, Hosseinzadeh, Sajadi, Alenaseri, Siavash, Jafari and Solgi.)

Despite low incidence, neuroblastoma, an immunologically cold tumor, is the most common extracranial solid neoplasm in pediatrics. In relapsed/refractory cases, the benefits of autologous hematopoietic stem cell transplantation (auto-HSCT) and other therapies are limited. Natural killer (NK) cells apply cytotoxicity against tumor cells independently of antigen-presenting cells and the adaptive immune system. The primary endpoint of this trial was to assess the safety of the injection of allogenic, ex vivo-expanded and primed NK cells in relapsed/refractory neuroblastoma patients after auto-HSCT. The secondary endpoint included the efficacy of this intervention in controlling tumors. NK cells were isolated and primed ex vivo (by adding interleukin [IL]-2, IL-15, and IL-21) in a GMP-compliant CliniMACS system and administered to four patients with relapsed/refractory MYCN-positive neuroblastoma. NK cell injections (1 and 5 × 10 7 cells/kg in the first and second injections, respectively) were safe, and no acute or sub-acute adverse events were observed. During the follow-up period, one complete response (CR) and one partial response (PR) were observed, while two cases exhibited progressive disease (PD). In follow-up evaluations, two died due to disease progression, including the case with a PR. The patient with CR had regular growth at the 31-month follow-up, and another patient with PD is still alive and receiving chemotherapies 20 months after therapy. This therapy is an appealing and feasible approach for managing refractory neuroblastomas post-HSCT. Further studies are needed to explore its efficacy with higher doses and more frequent administrations for high-risk neuroblastomas and other immunologically cold tumors.Trial registration number: irct.behdasht.gov.ir (Iranian Registry of Clinical Trials, No. IRCT20201202049568N1)., (© 2024. The Author(s).)

Background: Premenstrual syndrome (PMS) is characterized by physical, cognitive, emotional, and behavioral symptoms that appear during the luteal phase of the menstrual cycle, disappear after menstruation, and are recurrent in every cycle. PMS significantly affects the social and academic lives of adolescents, and historically, it has been neglected by healthcare professionals. We aimed to evaluate the current point prevalence of PMS in Turkish adolescents presented to a tertiary adolescent medicine clinic., Material and Method: Adolescent girls between the ages of 12 and 18 and who had regular menstrual cycles for at least three months without any mental or chronic illness were assessed. A clinic information form and the 'Premenstrual Syndrome Scale' (PMSS) questionnaire were completed. Those with a PMSS total score of more than 50% of the total score (>110 out of 220) were classified as PMS (+). Those classified as PMS were further classified as mild-moderate (score: 110-150) and severe (>150)., Results: The study included 417 adolescents. The point prevalence of PMS was found to be 61.2% (n:255). Of those with PMS, 49.4% had mild-moderate and 50.6% had severe PMS. The mean PMSS score was 154.56 ± 30.43 in the PMS group and 76.17 ± 20.65 in the non-PMS group (p<0.001). The mean age was 15.41 ± 1.3 years in the PMS group and 14.88 ± 1.35 years in the non-PMS group (p=0.029). None of the youth in our study applied to our clinic due to any premenstrual complaints., Conclusion: PMS is frequently observed in youth, as indicated by our study. Adolescents have little awareness of PMS and their need for healthcare services. During the evaluation of adolescents, it is important for health care providers to acquire knowledge regarding the features of menstrual cycles and conduct a comprehensive psychosocial assessment., Competing Interests: The authors declare that there is no conflict of interest.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative strategy against a variety of malignant and nonmalignant disorders. However, acute and chronic graft-versus-host disease (aGVHD and cGVHD, respectively) commonly complicate this approach, culminating in substantial morbidities and mortalities. The integumentary system is the preponderant organ involved in cGVHD, and its response to existing treatments, including well-versed immunosuppressants and novel targeted therapies, is not desirable. Despite the rarity, ulcers of sclerotic skin cGVHD are treatment-refractory and associated with significant morbidities and an exaggerated risk of infectious complications. Platelet-rich plasma (PRP) and its derivatives are endowed with growth factors and proangiogenic molecules and hold regenerative potential. This study aimed to assess the safety and efficacy of the application of platelet gel-containing dressing against ulcerative skin cGVHD in pediatric patients. This randomized trial is conducted at the hematopoietic stem cell transplantation unit of the Children's Medical Center Hospital in Tehran, Iran. Twenty-one pediatric patients (aged between 5 and 15 years) were initially enrolled, and 16 met the inclusion criteria. All cases (4 females) were recipients of allo-HSCT who had been complicated with symmetrically or near-symmetrically ulcerative sclerotic skin cGVHD. Fresh umbilical cord blood (UCB) was obtained from healthy donors and underwent centrifugation using a novel PRP preparation kit in a single-step process. Platelet gel was produced by adding thrombin to the isolated buffy coat layer. Two similar ulcers of each patient were randomized to receive either conventional dressing or platelet gels up to 6 times. At each time point evaluation, ulcer size and its relative reduction compared to the basal size were recorded. Included patients received a total of 80 platelet gel-containing dressings. While the mean sizes of randomized ulcers at the beginning of the study were similar, their differences became significant 15 days after the initiation of intervention (P = .019). In addition, the mean reduction in the ulcers' surface area (in comparison to their baseline values) was significantly higher for the intervention arm at all evaluation points (P = .001 for day 5 and P < .001 for subsequent time points). At the end of the trial, the number of ulcers with a more than 50% reduction in size was 14 (87.5%) in the intervention arm (including 6 completely healed ulcers) versus 1 (6.25%, which was not completely healed) in the control arm (P < .001). None of the patients exhibited any localized or systemic treatment-related adverse events. In this study, using a relatively large number of cases, we showed that UCB-derived platelet gel is a safe, feasible, and effective curative approach for skin ulcers of sclerotic skin cGVHD in pediatric patients. Designing upcoming trials on the efficacy of this therapeutic approach for ocular, mucosal, and acute skin GVHD is prudent. Retrospectively registered at the Iranian Registry of Clinical Trials (registration number IRCT20190101042197N1) on August 24, 2020., (Copyright © 2024 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

The molecular mechanisms of progressive right heart failure are incompletely understood. In this study, we systematically examined transcriptomic changes occurring over months in isolated cardiomyocytes or whole heart tissues from failing right and left ventricles in rat models of pulmonary artery banding (PAB) or aortic banding (AOB). Detailed bioinformatics analyses resulted in the identification of gene signature, protein and transcription factor networks specific to ventricles and compensated or decompensated disease states. Proteomic and RNA-FISH analyses confirmed PAB-mediated regulation of key genes and revealed spatially heterogeneous mRNA expression in the heart. Intersection of rat PAB-specific gene sets with transcriptome datasets from human patients with chronic thromboembolic pulmonary hypertension (CTEPH) led to the identification of more than 50 genes whose expression levels correlated with the severity of right heart disease, including multiple matrix-regulating and secreted factors. These data define a conserved, differentially regulated genetic network associated with right heart failure in rats and humans., (© 2024. The Author(s).)

Background: The aim of the study was to investigate the morphometric parameters of dental pulp in open apices immature teeth in a sheep model after mechanical pulp exposure and restoration with reinforced zinc oxide-eugenol., Materials and Methods: In this experimental study, a total of 12 immature mandibular central incisors from six adult male sheep, weighing 30-40 kg and with the age of 1 year old with Merino race were examined. After anesthesia, the pulps of the teeth in the case group were mechanically exposed and then were restored with reinforced zinc oxide-eugenol and amalgam. In the control group, the teeth remained intact. The animals were sacrificed at intervals of 2, 4, 6, and 8 weeks (E2, E4, E6, and E8) in the case and 2 and 8 weeks (C2 and C8) in the control groups. Then, their teeth were removed with the surrounding supporting tissues and alveolar bones. Tissue processing and staining were done, and the sections were examined under a light microscope. The Kruskal-Wallis and Mann-Whitney U tests were used to analyze the data and compare the changes between the two groups. P < 0.05 was considered statistically significant., Results: In response to mechanical exposure, reparative or tertiary dentin was formed, and its thickness increased during the time of the study. The thickness of the odontoblastic layer in the E4 group was the highest amount. The pulp chamber diameter in the C2 group was significantly larger than the other groups, and the diameter of the apical foramen in the E8 was decreased significantly compared to the controls ( P < 0.05)., Conclusion: In response to mechanical exposure and restoration with reinforced zinc oxide-eugenol, some morphometric parameters of the dental pulp changed significantly in the sheep model compared to the controls., Competing Interests: The authors of this manuscript declare that they have no conflicts of interest, real or perceived, financial or non-financial in this article., (Copyright: © 2024 Dental Research Journal.)

Introduction: Allogeneic hematopoietic stem cell transplantation (HSCT) is the only definitive curative option for β-major thalassemia patients (β-MT). Posterior reversible encephalopathy syndrome (PRES) is a pervasive neurological complication which typically occurs following HSCT. β-MT patients are prone to a higher PRES incidence due to long-term immunosuppression; thus, it is imperative that these patients are closely monitored for PRES after HSCT., Patients and Methods: We included 148 pediatric patients with β-MT who underwent HSCT between March 2015 and August 2022 in Children's Medical Center. Patients in this study were divided into two groups. The association between PRES and class of β-MT and other risk factors were assessed and the overall survival rate was determined., Results: Fourteen out of 112 patients (12%) with class I and II β-MT developed PRES. However, PRES occurred in 11 out of 36 patients (30.5%) with β-MT-III. Our results indicated that there was a significant association between class III β-MT and the occurrence of (P = .004). Additionally, acute graft-versus-host disease (aGVHD) occurred in 80% and 44.7% of patients in the PRES and non-PRES groups, respectively (P = .001). The results of the Kaplan-Meier analysis revealed that the 5-year overall survival (OS) was 75.6% in the PRES group versus 95% in the non-PRES group, which was statistically significant (P = .001)., Conclusion: Based on our results, pediatric β-MT III patients are at a higher risk of developing PRES. Additionally, pediatric β-MT patients with a history of aGVHD, regardless of disease class, are more likely to develop PRES. Considering these results, PRES has a higher chance of being the etiology of symptoms and should be considered more often in these patients., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: We aimed to evaluate the efficacy, safety, and latent toxicity of total body irradiation (TBI)-based conditioning regimens compared to non-TBI regimens for pediatric patients (under 18 years old) with acute lymphoblastic leukemia (ALL) undergoing allogeneic hematopoietic stem cell transplantation (HSCT)., Methods: A systematic search was performed on MEDLINE, Scopus, WOS, and PMC. Also, a search for grey literature was performed on Google Scholar and relevant articles' references were included. Relevant articles which met the inclusion criteria were retrieved up to October 31th, 2022. CMA version 2 was used for the quantitative synthesis of the data., Results: Eight studies on efficacy and safety of TBI and non-TBI as a conditioning regimen were analyzed and six comparative studies on late toxicity were investigated. The meta-analysis revealed a hazard ratio (HR) of 1.508 (95% CI 0.96-2.35) for overall survival (OS) in instances of non-TBI conditioning. Also, an HR of 1.503 (95% CI 1.006-2.25) for disease-free- survival (DFS) favoring TBI-based conditioning. Late complications were reported to be significantly higher in the TBI conditioning regimen group than in the non-TBI group., Conclusion: It appears that non-TBI regimens are as effective as TBI regimens in pediatrics with ALL regarding OS. Occurrence of latent toxicity is higher with TBI conditioning regimen. Conversely, TBI-based regimens are superior to non-TBI conditioning regimens regarding DFS. Considering all aspects, non-TBI conditioning regimens can be an alternative treatment option for pediatric ALL undergoing HSCT., Competing Interests: Declaration of Competing Interest All of the authors declare that there is no conflict of interest., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Smoking is clearly associated with metabolic profiles/abnormalities, psychological dysfunction, and symptoms of nicotine dependence. Nano-Curcumin (Nano-CUR) is a medicinal herb with antianxiety, antioxidant antidepressant-like effects, and anti-inflammatory properties. This RCT aimed to determine the therapeutic effects of Nano-CUR in smokers on clinical symptoms and metabolic parameters., Methods: This trial was conducted on 70 participants with cigarette smoking. Smokers in two arms received soft gel capsules Nano-CUR 80 mg/daily for 3 months (n = 35) and placebo (n = 35), respectively. Primary outcomes (Nicotine dependence syndrome scale, depression, and anxiety beck score), and secondary outcomes (glycemic, lipid, stress oxidative, and inflammation profiles) were analyzed before and 3-months after the intervention in smokers., Results: Nano-CUR supplementation significantly decreased nitric oxide, malondialdehyde, and C-reactive protein levels (P < 0.05), compared to the control. Furthermore, no significant effect change was shown in nicotine dependence syndrome, depression, anxiety, and other metabolic parameters (p > 0.05)., Conclusion: Nano-CUR intake may have favorable effects on C-reactive protein, malondialdehyde, and nitric oxide in subjects with cigarette smoking. More RCT are required to evaluate the effectiveness of Nano-CUR supplementations in smokers in order to reject or support these conclude., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Background: Heterosis is a complex phenomenon wherein the hybrids outperform their parents. Understanding the underlying molecular mechanism by which hybridization leads to higher yields in allopolyploid cotton is critical for effective breeding programs. Here, we integrated DNA methylation, transcriptomes, and small RNA profiles to comprehend the genetic and molecular basis of heterosis in allopolyploid cotton at three developmental stages., Results: Transcriptome analysis revealed that numerous DEGs responsive to phytohormones (auxin and salicylic acid) were drastically altered in F1 hybrid compared to the parental lines. DEGs involved in energy metabolism and plant growth were upregulated, whereas DEGs related to basal defense were downregulated. Differences in homoeologous gene expression in F1 hybrid were greatly reduced after hybridization, suggesting that higher levels of parental expression have a vital role in heterosis. Small RNAome and methylome studies showed that the degree of DNA methylation in hybrid is higher when compared to the parents. A substantial number of allele-specific expression genes were found to be strongly regulated by CG allele-specific methylation levels. The hybrid exhibited higher 24-nt-small RNA (siRNA) expression levels than the parents. The regions in the genome with increased levels of 24-nt-siRNA were chiefly related to genes and their flanking regulatory regions, demonstrating a possible effect of these molecules on gene expression. The transposable elements correlated with siRNA clusters in the F1 hybrid had higher methylation levels but lower expression levels, which suggest that these non-additively expressed siRNA clusters, reduced the activity of transposable elements through DNA methylation in the hybrid., Conclusions: These multi-omics data provide insights into how changes in epigenetic mechanisms and gene expression patterns can lead to heterosis in allopolyploid cotton. This makes heterosis a viable tool in cotton breeding., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Fibroblast growth factor 23 (FGF-23) has been associated with left ventricular hypertrophy (LVH) and heart failure. However, its role in right ventricular (RV) remodeling and RV failure is unknown. This study analyzed the utility of FGF-23 as a biomarker of RV function in patients with pulmonary hypertension (PH)., Methods: In this observational study, FGF-23 was measured in the plasma of patients with PH (n = 627), dilated cardiomyopathy (DCM, n = 59), or LVH with severe aortic stenosis (n = 35). Participants without LV or RV abnormalities served as controls (n = 36)., Results: Median FGF-23 plasma levels were higher in PH patients than in healthy controls (p < 0.001). There were no significant differences between PH, DCM, and LVH patients. Analysis across tertiles of FGF-23 levels in PH patients revealed an association between higher FGF-23 levels and higher levels of NT-proBNP and worse renal function. Furthermore, patients in the high-FGF-23 tertile had a higher pulmonary vascular resistance (PVR), mean pulmonary artery pressure, and right atrial pressure and a lower cardiac index (CI) than patients in the low tertile (p < 0.001 for all comparisons). Higher FGF-23 levels were associated with higher RV end-diastolic diameter and lower tricuspid annular plane systolic excursions (TAPSE) and TAPSE/PASP. Receiver operating characteristic analysis revealed FGF-23 as a good predictor of RV maladaptation, defined as TAPSE < 17 mm and CI < 2.5 L/min/m 2 . Association of FGF-23 with parameters of RV function was independent of the glomerular filtration rate in regression analysis., Conclusion: FGF-23 may serve as a biomarker for maladaptive RV remodeling in patients with PH., (© 2023. The Author(s).)

Background: Allo-HSCT is a definite approach for the management of a wide variety of lethal and debilitating malignant and non-malignant disorders. However, its two main complications, acute and chronic graft-versus-host disease (GVHD), exert significant morbidities and mortalities. BoS, as a manifestation of chronic lung GVHD, is a gruesome complication of allo-HSCT, and for those with steroid-refractory disease, no approved second-line therapies exist. Mesenchymal stem cells (MSCs) exert anti-inflammatory and growth-promoting effects, and their administration against a wide range of inflammatory and neurologic disorders, as well as GVHD, has been associated with promising outcomes. However, literature on the safety and effectiveness of MSC therapy for BoS and pediatric cGVHD is scarce., Methods: We designed a single-arm trial to administer adipose tissue (AT)-derived MSCs to pediatric patients with refractory BoS after allo-HSCT. AT-MSCs from obese, otherwise healthy donors were cultured in an ISO class 1 clean room and injected into the antecubital vein of eligible patients with a dose of 1 × 10 6 /kg. The primary endpoints included a complete or partial response to therapy [in terms of increased forced expiratory volume in one second (FEV1) values and steroid dose reduction] and its safety profile., Results: Four eligible patients with a median age of 6.5 years were enrolled in the study. Steroid-induced osteoporosis and myopathy were present in three cases. A partial response was evident in three cases after a single injection of AT-MSCs. The treatment was safe and tolerable, and no treatment-related adverse events were noted. Two patients developed manageable COVID-19 infections one and 4 months after AT-MSC injection. After a median follow-up duration of 19 months, all cases are still alive and have had no indications for lung transplantation., Conclusions: AT-MSCs could be safely administered to our pediatric cases with BoS post-allo-HSCT. Considering their advanced stage of disease, their sub-optimal functional capacity due to steroid-induced complications, and COVID-19 infection post-treatment, we believe that AT-MSC therapy can have possible efficacy in the management of pediatric BoS. The conduction of further studies with larger sample sizes and more frequent injections is prudent for further optimization of AT-MSC therapy against BoS. Trial registration Iranian Registry of Clinical Trials (IRCT), IRCT20201202049568N2. Registered 22 February 2021, https://en.irct.ir/trial/53143 ., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: The ability of the right ventricle (RV) to adapt to an increased pressure afterload determines survival in patients with pulmonary arterial hypertension. At present, there are no specific treatments available to prevent RV failure, except for heart/lung transplantation. The wingless/int-1 (Wnt) signaling pathway plays an important role in the development of the RV and may also be implicated in adult cardiac remodeling., Methods: Molecular, biochemical, and pharmacological approaches were used both in vitro and in vivo to investigate the role of Wnt signaling in RV remodeling., Results: Wnt/β-catenin signaling molecules are upregulated in RV of patients with pulmonary arterial hypertension and animal models of RV overload (pulmonary artery banding-induced and monocrotaline rat models). Activation of Wnt/β-catenin signaling leads to RV remodeling via transcriptional activation of FOSL1 and FOSL2 (FOS proto-oncogene [FOS] like 1/2, AP-1 [activator protein 1] transcription factor subunit). Immunohistochemical analysis of pulmonary artery banding -exposed BAT-Gal (β-catenin-activated transgene driving expression of nuclear β-galactosidase) reporter mice RVs exhibited an increase in β-catenin expression compared with their respective controls. Genetic inhibition of β-catenin, FOSL1/2, or WNT3A stimulation of RV fibroblasts significantly reduced collagen synthesis and other remodeling genes. Importantly, pharmacological inhibition of Wnt signaling using inhibitor of PORCN (porcupine O-acyltransferase), LGKK-974 attenuated fibrosis and cardiac hypertrophy leading to improvement in RV function in both, pulmonary artery banding - and monocrotaline-induced RV overload., Conclusions: Wnt- β-Catenin-FOSL signaling is centrally involved in the hypertrophic RV response to increased afterload, offering novel targets for therapeutic interference with RV failure in pulmonary hypertension., Competing Interests: Disclosures None.

Background: Acute lymphoblastic leukemia (ALL) is the most prevalent childhood cancer under the age of 15 years. Despite the recent advances in therapeutic regimens, relapse occurs in 15%-20% of pediatric patients after chemotherapy, and hematopoietic stem cell transplantation (HSCT) is the best treatment option. However, donor availability is one of the major challenges. Over the last decade, haploidentical donor (HID) transplantation has evolved as an alternative option. Herein, we aimed to compare the transplant outcomes in pediatric patients receiving total body irradiation (TBI)-free myeloablative regimens, between non-HID and HID transplant., Patients and Methods: The study included 60 pediatric ALL patients who had undergone HSCT from October 2016 until September 2020. Forty-three patients received non-HID HSCT, while 17 patients received HID. The sources of stem cells (SC) were peripheral blood stem cells (PBSC) for all the patients. The conditioning regimen was based on busulfan and cyclophosphamide. For graft-versus-host disease (GvHD) prophylaxis, patients received cyclosporine and methotrexate in the setting of non-HID transplantation, where HIDs received post-transplant cyclosporine and cyclophosphamide., Results: The cumulative incidences of 3-year overall survival (OS) were 73.1%, 66.6%, and 69.5%, for matched sibling donor-matched related donor (MSD-MRD), matched unrelated donor-mismatched unrelated donor (MUD-MMUD), and HID groups, respectively (p = .85). The cumulative incidences of grade II-IV acute GvHD for the MRD, MUD-MMUD, and HID groups were 29%, 41%, and 49%, respectively (p = .47). Furthermore, the 3-year cumulative incidence of chronic GvHD was MSD-MRD: 70% versus MUD-MMUD: 42% versus HID: 45% (p = .64). The 3-year cumulative incidence of relapse post transplantation was 45%, 18%, and 45%, respectively, for the MSD-MRD, MUD-MMUD, and HID groups, and the differences were not statistically significant (p = .55). There was a higher risk for cytomegalovirus (CMV) infection in patients receiving HID transplants compared to those of non-HIDs (p < .01)., Conclusion: Our results indicate that PBSC-HID transplant outcomes in the setting of non-TBI conditioning are comparable to those of non-HIDs in pediatric ALL patients., (© 2023 Wiley Periodicals LLC.)

Background: Male infertility due to very severe oligozoospermia has been associated with some genetic risk factors., Objective: To investigate the distribution of the mutations in the CFTR gene, the CAG-repeat expansion of the AR gene, also Y chromosome microdeletions and karyotyping abnormalities in very severe oligozoospermia patients., Methods: In the present case-control study, 200 patients and 200 fertile males were enrolled. All patients and control group were karyotyped. Microdeletions were evaluated using multiplex PCR. Five common CFTR mutations were genotyped using the ARMS-PCR technique. The CAG-repeat expansion in the AR gene was evaluated for each individual using sequencing., Results: Overall 4% of cases shows a numerical and structural abnormality. 7.5% of patients had a deletion in one of the AZF regions on Yq, and 3.5% had a deletion in two regions. F508del was the most common (4.5%) CFTR gene mutation; G542X, and W1282X were detected with 1.5% and 1% respectively. One patient was found to have AZFa microdeletion and F508del in heterozygote form; one patient had AZFb microdeletion with F508del. F508del was seen as compound heterozygous with G542X in one patient and with W1282X in the other patient. The difference in the mean of the CAG-repeats in the AR gene in patients and control groups was statistically significant (P = 0.04)., Conclusion: Our study shows the genetic mutations in men with severe oligozoospermia and given the possibility of transmission of these disorders to the next generation by fertilization, counseling and genetic testing are suggested for these couples before considering ICSI., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

The eminence of Bacillus Calmette-Guerin (BCG) vaccine in newborn vaccination programs has been conspicuous throughout the years, especially in low-income developing countries where tuberculosis is prevalent; however, application of the BCG vaccine is not without constraints, especially in patients afflicted with immunodeficiency diseases, such as severe combined immunodeficiency (SCID). The present study aimed to evaluate whether the administration of BCG vaccine at birth could improve the outcomes of hematopoietic stem cell transplantation (HSCT) in pediatric patients with SCID. In this study, 30 SCID patients who underwent HSCT using a reduced-intensity conditioning regimen (RIC) were followed-up for 2 years post-HSCT. The outcomes of HSCT were evaluated in both non-BCG-vaccinated patients (n = 12) and BCG-vaccinated patients (n = 18). Our results show a higher incidence of acute graft-versus-host disease (aGVHD), but not of chronic GVHD, in the BCG-vaccinated patients, and a similar overall survival (OS) rate in the 2 groups. We speculate that the similar OS rate in the 2 groups, despite the risk of BGC vaccination, was because this group received an RIC conditioning regimen. There was no other difference between the 2 groups. Considering the effect of the BCG vaccine on HSCT outcome, we suggest that the administration of BCG vaccine be deferred until age 3 months so that APT testing without the interference of maternal antibodies can be performed. However, this study could benefit from a larger cohort to further validate our findings, as the possible reason for some factors not being statistically significant was our small sample size., (Copyright © 2022 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Climate change is one of the biggest environmental challenges that significantly impact water resources and the quantity and quality of agricultural products. Assessment of these impacts during the historical period and under future climate is essential for achieving a sustainable agricultural system in the face of climate change threats and water scarcity. In this research, we evaluated the yield and water footprint of rainfed and irrigated wheat during the historical period (1986-2015) and two future periods (2016 to 2055) in a semi-arid environment in Fars province, Iran. The future climate data was selected from the CanESM2 model outputs (bias-corrected and downscaled using the SDSM model) under the RCP4.5 scenario, and the yield projection was made using the AquaCrop model. Our result showed that for both irrigated and rainfed wheat, the yield significantly increases in southern parts of the study area in future climates, primarily because of an increase in effective precipitation. Other regions will experience a marginal yield decrease or no yield changes (in the case of irrigated wheat). Our assessments of the water footprint of wheat production showed a significant reduction in green and blue water footprints in the southern regions. In other regions, various patterns emerged for irrigated and rainfed wheat, but an overall increase was observed. The southern regions of the study area will be more suitable for wheat production owing to the higher yield and lower water footprint., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Differential diagnosis of chronic lymphoproliferative disorders (CLDs) has remained challenging due to the highly variable morphology features and immunophenotyping. Currently, the development of multiple-marker panel analyses by flow cytometry has opened a broad way for diagnosis of CLDs., Methods: We analyzed the peripheral blood and bone marrow samples of 131 patients with B-cell CLDs (including 91 chronic lymphocytic leukemia (CLL), 15 atypical CLL, 14 mantle cell lymphoma (MCL), and 11 CD5-/CD10-lymphoma patients) from April 2018 to April 2019, using a panel of specific markers by flow cytometry., Results: Our results indicated that the expression pattern of CD22, CD23, FMC-7, and CD5 allowed us to accurately and differentially diagnose the B-CLL, MCL, and CD5-/CD10- lymphoma, while it was not capable of differentiating MCL from atypical CLL. We, however, found that the expression patterns of CD38 and immunoglobulin light chain differed significantly between atypical B-CLL and MCL. CD38 and lambda light chain were remarkably expressed in MCL patients (92.8% and 85%, respectively) compared to the atypical CLL (1.1% and 0% respectively), with the p value less than 0.001 for both markers. In contrast to MCL patients, all the patients with atypical CLL, expressed kappa light chain. The immunohistochemistry method used for cyclin D1 confirmed that the flow cytometry detection of kappa and lambda light chains could provide a new approach with high sensitivity (91%) and moderate specificity (50%) to distinguish MCL patients from atypical B-CLL., Conclusion: Expression of CD5, CD20 (bright), CD22, FMC-7, CD38, and lambda light chain with no expression of CD23 can accurately detect MCL and differentiate it from atypical B-CLL

Background: This study analyzed the utility of soluble ST2 (sST2) and GDF-15 as biomarkers of right ventricular (RV) function in patients with pulmonary hypertension (PH). Methods: GDF-15 and sST2 serum concentrations were measured in patients with PH (n = 628), dilated cardiomyopathy (n = 31) and left ventricular hypertrophy (n = 47), and in healthy controls (n = 61). Results: Median sST2 and GDF-15 levels in patients with left ventricular hypertrophy were higher than in patients with PH and dilated cardiomyopathy. In tertile analysis GDF-15 >1363 pg/ml and sST2 >38 ng/ml were associated with higher N-terminal pro-brain natriuretic peptide, RV systolic dysfunction, RV-pulmonary arterial uncoupling and hemodynamic impairment. Conclusion: GDF-15 and sST2 are potential biomarkers of RV dysfunction in patients with PH.

Background: Recently, the non-toxic properties of natural plant products have gained more focus as anticancer agents. Therefore, this study aimed to assess the apoptosis effects of the ethanolic extract of Oxalis corniculata on the MCF-7 breast cancer cell line. Materials and Methods: In this experimental study, aerial parts of O. corniculata were collected in Lahijan city (Iran), and after confirmation, they were dried and extracted with ethanol for 24 h. Then, the total phenolic and flavonoid contents of the extract were measured. The 2,2-diphenyl-1-picrylhydrazyl radical scavenging assay was used to measure the antioxidant properties of the extract. Selected cell lines (MCF-7 and human dermal fibroblast) were cultured in 6-wells dishes (1×10 6 cells/well). After 72 h of treating the extract, cytotoxicity was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The expression of apoptotic genes (such as p53 , bcl-2 , bax , and CD95 ) was studied by real-time polymerase chain reaction (PCR). Results: The extract's total phenolic content was 31.30±02 μg of gallic acid equivalents/mg of dry extract, and the total flavonoid content was 49.61±04 μg of quercetin as equivalents/mg of extract. The antioxidant activity of O. corniculata was measured at the dose of 619.2 μg/μl, indicating that it decreases cancer cell viability and enhances apoptosis. Within the half maximal inhibitory concentrations, real-time PCR revealed substantial increases in p53 (P<0.001), CD95 (P<0.05), and bcl-2 expression (P<0.05) in MCF-7 cells treated with O. corniculata . Conclusion: This study suggests that O. corniculata may cause apoptosis by oxidative stress in cancer cells.[GMJ.2022;11:e2484]., (Copyright© 2022, Galen Medical Journal.)

Background: Despite the obvious violation of women's rights in Pakistan and the vital necessity for women empowerment, a unified country-specific index measuring women empowerment is not yet available. This study cross-validated a survey-based women empowerment index from Afghanistan to be used in Pakistan., Methods: The data for married Pakistani women aged 15-49 in the 2017-18 Pakistan demographic health survey was used to construct the final model using the explanatory and confirmatory factor analyses. The Cronbach's alpha test examined the internal consistency of the developed index. To assess the convergence validity of the index, the association of each emerged domain with indicators of access to reproductive and maternity care was assessed by Poisson regression analysis adjusting for wealth index., Results: The final index had six domains; namely, labor force participation, attitude toward violence, decision-making, access to healthcare, literacy, age at critical life events predicting women empowerment of married Pakistani women with decent reliability (Cronbach's α = 0.70), and validity (SRSEA&SRMR < 0.05, CFI&TLI > 0.92). The emerged domains were significantly associated with at least one of four indicators for access to reproductive and maternity care; indicative of a favorable convergence validity., Conclusion: Pakistan and Afghanistan are associated as brother countries with shared religious and ethnocultural identities in which women are perceived inferior to men and in critical need of empowering efforts. The results of this study reflect upon this resemblance in sociocultural structure by yielding similar domains for women's empowerment in Pakistan building upon an index previously developed for Afghan women. The developed index could inform the design of future policies, interventions, and research recognizing the important indicators of women empowerment in Pakistan and could enhance the comparability of the results across future studies., (© 2022. The Author(s).)

Ongoing novel coronavirus (COVID-19) with high mortality is an infectious disease in the world which epidemic in 2019 with human-human transmission. According to the literature, S-protein is one of the main proteins of COVID-19 that bind to the human cell receptor angiotensin-converting enzyme 2 (ACE2). In this study, it was attempted to identify the main effective drugs approved that may be repurposed to the binding site of ACE2. High throughput virtual screening based on the docking study was performed to know which one of the small-molecules had a potential interaction with ACE2 structure. Forasmuch as investigating and identifying the best ACE2 inhibitors among more than 3,500 small-molecules is time-consuming, supercomputer was utilized to apply docking-based virtual screening. Outputs of the proposed computational model revealed that vincristine, vinbelastin and bisoctrizole can significantly bind to ACE2 and may interface with its normal activity., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of Medical Signals & Sensors.)

Background: Drug resistance in breast cancer is an unsolved problem in treating patients. It has been recently discussed that lysosomes contribute to the invasion and angiogenesis of cancer cells. There is evidence that lysosomes can also cause multi-drug resistance. We analyzed this emerging concept in breast cancer through computational and systems biology approaches., Objectives: We aimed to identify the key lysosome-related genes associated with drug-resistant breast cancer., Methods: All genes contributing to the structure and function of lysosomes were inquired through the Human Lysosome Gene Database. The prioritized top 51 genes from the provided lists of Endeavour, ToppGene, and GPSy as prioritization tools were selected. All lysosomal genes and 12 breast cancer-related genes aligned to identify the most similar genes to breast cancer-related genes. Different centralities were applied to score each human protein to calculate the most central lysosomal genes in the human protein-protein interaction (PPI) network. Common genes were extracted from the results of the mentioned methods as a selected gene set. For Gene Ontology enrichment, the selected gene set was analyzed by WebGestalt, DAVID, and KOBAS. The PPI network was constructed via the STRING database. The PPI network was analyzed utilizing Cytoscape for topology network interaction and CytoHubba to extract hub genes., Results: Based on biological studies, literature reviews, and comparing all mentioned analyzing methods, six genes were introduced as essential in breast cancer. This computational approach to all lysosome-related genes suggested that candidate genes include PRF1, TLR9, CLTC, GJA1, AP3B1, and RPTOR. The analyses of these six genes suggest that they may have a crucial role in breast cancer development, which has rarely been evaluated. These genes have a potential therapeutic implication for new drug discovery for chemo-resistant breast cancer., Conclusions: The present work focused on all the functional and structural lysosome-related genes associated with breast cancer. It revealed the top six lysosome hub genes that might serve as therapeutic targets in drug-resistant breast cancer. Since these genes play a pivotal role in the structure and function of lysosomes, targeting them can effectively overcome drug resistance., Competing Interests: Conflict of Interests: The authors declare no conflict of interest., (Copyright © 2022, Author(s).)

Due to progress in infertility etiology, several genetic bases of infertility are revealed today. This study aimed to investigate the distribution of mutations in the CFTR gene, M470V polymorphism, and IVS8 poly T. Furthermore, we aimed to examine the hotspot exons (4, 7, 9, 10, 11, 20, and 21 exons) to find a new mutation in cystic fibrosis transmembrane conductance regulator (CFTR) gene among infertile Iranian men very severe oligozoospermia (<1 million sperm/mL ejaculate fluid). In the present case-control study, 200 very severe oligozoospermia (20-60s) and 200 fertile men (18-65s) were registered. Five common CFTR mutations were genotyped using the ARMS-PCR technique. The M470V polymorphism was checked out by real-time PCR, and poly T and exons were sequenced. The F508del was the most common (4.5%) CFTR gene mutation; G542X and W1282X were detected with 1.5% and 1%, respectively. N1303K and R117H were detected in 0.5% of cases. F508del was seen as a heterozygous compound with G542X in one patient and with W1282X in the other patient. Also, in the case of M470V polymorphism, there are differences between the case and control groups (p=0.013). Poly T assay showed statistical differences in some genotypes. The study showed no new mutation in the exons mentioned above. Our results shed light on the genetic basis of men with very severe oligozoospermia in the Iranian population, which will support therapy decisions among infertile men., (©2022 JOURNAL of MEDICINE and LIFE.)

The aim of this study was to evaluate the cartilage intermediate layer protein 1 (CILP1) as a biomarker of right ventricular dysfunction in patients with ischemic cardiomyopathy (ICM). CILP1 plasma concentrations were measured in 98 patients with ICM and 30 controls without any cardiac abnormalities. All participants underwent cardiac magnetic resonance imaging. Median CILP1 concentrations were higher in ICM than in controls. In the tertile analysis, low right ventricular ejection fraction (RVEF) and high right ventricular end-systolic volume index and N-terminal pro-brain natriuretic peptide (NT-proBNP) were associated with higher CILP1 levels in ICM. However, there were no associations between CILP1 concentrations and left ventricular (LV) parameters in this group. In receiver-operating characteristic (ROC) analysis CILP1 was a good predictor of RVEF < 40% with an optimal cut-off value of 3545 pg/ml in ICM, whereas it was not predictive of LV ejection fraction (LVEF) < 40% (area under the curve [AUC] = 0.57) There was no significant difference between the ROC curves of CILP1 (AUC = 0.72) and NT-proBNP (AUC = 0.77) for RVEF < 40% ( p  = 0.42). In multivariable regression analysis, RVEF was the only independent predictor of elevated CILP1. CILP1 and LVEF were the only independent predictors of RVEF < 40% in ICM. Our analysis demonstrates the potential role of CILP1 as a novel cardiac biomarker of prognostically relevant RV dysfunction in patients with ICM., Competing Interests: The authors declare no conflicts of interest., (© 2022 The Authors. Pulmonary Circulation published by Wiley Periodicals LLC on behalf of the Pulmonary Vascular Research Institute.)

Concerns about the negative effects of declining agricultural biodiversity due to modern agricultural practices and climatic constraints in various parts of the world, including Iran, on the sustainability of agricultural ecosystems are increasingly growing. However, the historical knowledge of temporal and spatial biodiversity is lacking. To determine the value and trend of crop diversity in Iran, we used biodiversity indices based on the area under rainfed and irrigated crops and total cropland area from 1991 to 2018. There were large fluctuations in the amount of cultivated area in the past 30 years, peaking around 2005 to 2007 with about 13.1 million cultivated hectares. However, no general trend in increase or decrease of total cultivated land was shown. The crop species diversity of irrigated cropland was higher than the rainfed and total cropland. The Shannon diversity index showed a constant trend with a negligible slope, but species richness was increased, which was related to the rise in the area of some crop species in recent years. The area of wheat and barley had a significant impact on crop diversity, so Shannon diversity index reduced with their dominance. Overall, this study revealed that the Iranian agricultural system relies on wheat and barley. We warn that by increasing the area of these crops and the prevalence of monoculture, the probability of damage from external factors such as sudden weather changes or the spread of diseases will increase, leading to instability and production risks in the future., Competing Interests: The authors have declared that no competing interests exist.