Marine turtles as bio-indicators of plastic pollution in the eastern Mediterranean.

The loggerhead turtle (Caretta caretta) has been suggested as a bio-indicator species for plastic pollution. However, detailed investigations in the eastern Mediterranean are limited. Here, we present data from loggerhead turtles (2012-2022; n = 131) of which 42.7 % (n = 57) had ingested macroplastic (pieces ≥ 5 mm). Frequency of occurrence (%) was not found to have changed over time, with body size (CCL cm), between stranded or bycaught turtles, or with levels of digesta present. The characteristics of ingested plastic (n = 492) were largely sheetlike (62 %), clear (41 %) or white (25 %) and the most common polymers identified were Polypropylene (37 %) and Polyethylene (35 %). Strong selectivity was displayed towards certain types, colours and shapes. Data are also presented for posthatchling turtles (n = 4), an understudied life stage. Much larger sample sizes will be needed for this species to be an effective bio-indicator, with the consideration of monitoring green turtles (Chelonia mydas) for the eastern Mediterranean recommended allowing a more holistic picture to be gathered.

CerS6-dependent ceramide synthesis in hypothalamic neurons promotes ER/mitochondrial stress and impairs glucose homeostasis in obese mice.

Dysregulation of hypothalamic ceramides has been associated with disrupted neuronal pathways in control of energy and glucose homeostasis. However, the specific ceramide species promoting neuronal lipotoxicity in obesity have remained obscure. Here, we find increased expression of the C16:0 ceramide-producing ceramide synthase (CerS)6 in cultured hypothalamic neurons exposed to palmitate in vitro and in the hypothalamus of obese mice. Conditional deletion of CerS6 in hypothalamic neurons attenuates high-fat diet (HFD)-dependent weight gain and improves glucose metabolism. Specifically, CerS6 deficiency in neurons expressing pro-opiomelanocortin (POMC) or steroidogenic factor 1 (SF-1) alters feeding behavior and alleviates the adverse metabolic effects of HFD feeding on insulin sensitivity and glucose tolerance. POMC-expressing cell-selective deletion of CerS6 prevents the diet-induced alterations of mitochondrial morphology and improves cellular leptin sensitivity. Our experiments reveal functions of CerS6-derived ceramides in hypothalamic lipotoxicity, altered mitochondrial dynamics, and ER/mitochondrial stress in the deregulation of food intake and glucose metabolism in obesity.

The role of eosinophil as a diagnostic, differential, and prognostic marker for Covid-19 during pregnancy: Case-control study from tertiary center.

PURPOSE: To evaluate the level of eosinophil count in Covid-19 pregnant patients as a cost-effective tool for aiding in diagnosis, differential diagnosis, and prognosis and, to assess whether eosinopenia could be similar or superior to lymphopenia in pregnancy with Covid-19. METHODS: Retrospective case-control study was conducted including pregnant women tested simultaneously for SARS-CoV-2 by RT-PCR and complete blood count (CBC). Eosinophil counts (EOS), lymphocytes (LYM), neutrophils (NEU) with calculation of EOS/LYM ratio, EOS/NEU ratio, NEU/LYM ratio, LYM/NEU ratio (LNR), eosinopenia, and lymphopenia were compared between the groups. ROC analysis was performed for determination of optimal cut-off values and comparative analysis between AUC were performed using the paired sample design. Logistic regression was used to determine the factors affecting the categorical variables. RESULTS: Four thousand two hundred sixteen pregnant women were included in the final analysis of which (n = 845) as healthy control group, (n = 1482) as non Covid-19 patient group and (n = 1889) as Covid-19 group. Covid-19 group was divided into three subgroups based on severity. To diagnose and distinguish Covid-19 from other infectious conditions, EOS had better performance with higher area under curve (AUC) (0.769 and 0.757 AUC, respectively, p < 0.001). Categorically, eosinopenia had better diagnostic (Covid-19 vs. healthy), prognostic (severe-critical vs. mild-moderate), and differential diagnostic (Covid-19 vs. non Covid-19) performance than lymphopenia (OR = 5.5 vs. 3.4, OR = 3.4 vs. 1.8, OR = 5.4 vs. 2.7 p = 0.000). CONCLUSION: Eosinopenia is a low-cost, reliable, and convenient marker for Covid-19 not only in diagnosis, but also in prognosis by acting as an early marker for predicting severe-critical cases.

Adverse outcomes and maternal complications in pregnant women with severe-critical COVID-19: a tertiary center experience.

OBJECTIVES: This study aimed to present perinatal outcomes, clinical challenges, and basic ICU management in pregnant women with severe-critical COVID-19 at our tertiary referral center. METHODS: In this prospective cohort study, patients were divided into two groups, whether they survived or not. Clinical characteristics, obstetric and neonatal outcomes, initial laboratory test results and radiologic imaging findings, arterial blood gas parameters at ICU admission, and ICU complications and interventions were compared between groups. RESULTS: 157 of the patients survived, and 34 of the patients died. Asthma was the leading health problem among the non-survivors. Fifty-eight patients were intubated, and 24 of them were weaned off and discharged healthfully. Of the 10 patients who underwent ECMO, only 1 survived (p<0.001). Preterm labor was the most common pregnancy complication. Maternal deterioration was the most common indication for a cesarean section. Higher neutrophil-to-lymphocyte-ratio (NLR) values, the need for prone positioning, and the occurrence of an ICU complication were important parameters that influenced maternal mortality (p<0.05). CONCLUSIONS: Overweight pregnant women and pregnant women with comorbidities, especially asthma, may have a higher risk of mortality related to COVID-19. A worsening maternal health condition can lead to increased rates of cesarean delivery and iatrogenic prematurity.

Nutrient-sensing AgRP neurons relay control of liver autophagy during energy deprivation.

Autophagy represents a key regulator of aging and metabolism in sensing energy deprivation. We find that fasting in mice activates autophagy in the liver paralleled by activation of hypothalamic AgRP neurons. Optogenetic and chemogenetic activation of AgRP neurons induces autophagy, alters phosphorylation of autophagy regulators, and promotes ketogenesis. AgRP neuron-dependent induction of liver autophagy relies on NPY release in the paraventricular nucleus of the hypothalamus (PVH) via presynaptic inhibition of NPY1R-expressing neurons to activate PVHCRH neurons. Conversely, inhibiting AgRP neurons during energy deprivation abrogates induction of hepatic autophagy and rewiring of metabolism. AgRP neuron activation increases circulating corticosterone concentrations, and reduction of hepatic glucocorticoid receptor expression attenuates AgRP neuron-dependent activation of hepatic autophagy. Collectively, our study reveals a fundamental regulatory principle of liver autophagy in control of metabolic adaptation during nutrient deprivation.

Fetal neurosonography in pregnant women recovering from COVID-19 disease.

OBJECTIVE: To investigate the effect of severe acute respiratory virus 2 (SARS-CoV-2) on fetal neurodevelopment in pregnant women. METHODS: This prospective cohort study included 54 pregnant women at least 4 weeks after the SARS-CoV-2 infection and 58 controls. In the third trimester, the depths of the fetal insula, Sylvian, parieto-occipital, and calcarine fissures, the length of cavum septum pellucidum (CSP), and the thickness of the corpus callosum (CC) were measured. Sylvian fissure operculization and cortical development were graded. The correlation analysis between fetal cortical development and Sylvian fissure operculization was performed with the Pearson test. RESULTS: The calcarine fissure depth and CC thickness were reduced in the study group (P < 0.001, P = 0.004). The fetal CSP length and ratio were increased in the study group (P = 0.016, P = 0.039). Approximately half of the study group fetuses had grade 4 or less Sylvian fissure operculization. The study group had a significantly higher rate of fetuses with grade 2 (31.5% vs. 13.8%) and significantly lower rate of fetuses with grade 4 cortical development (14.8% vs. 31.0%), compared with the controls. There was a moderate negative significant correlation between pregnant women recovering from COVID-19 and fetal cortical development and Sylvian fissure operculization (P = 0.001). CONCLUSION: This is the first study to investigate fetal cortical development in pregnant women recovering from COVID-19. The results indicate that COVID-19 disease may affect fetal neurodevelopment.

Comparison of cord blood pro-BNP levels in newborns of SARS-COV-2-positive and -negative women, and its association with adverse perinatal outcomes.

OBJECTIVE: To compare umbilical cord blood pro-B-type natriuretic peptide (BNP) levels in newborns of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) positive pregnancies to those of SARS-COV-2 negative pregnancies. METHODS: Prospectively cord blood samples from newborns of 42 SARS-COV-2 positive women, and 42 negative pregnant were collected at birth and analyzed for pro-BNP levels. RESULTS: The mean cord blood pro-BNP level was significantly higher in newborns of SARS-COV-2 positive women than in controls. Furthermore, the pro-BNP level was an independent predictor of NICU admission in both SARS-COV-2 positive and control patients. CONCLUSION: Cord blood pro-BNP level may be a parameter that can predict the under-stress fetus and adverse perinatal outcomes especially, in cases where placental involvement is present as in SARS-COV-2 infection.

The impact of covid-19 on thyroid function tests in pregnancy.

PURPOSE: To investigate the effects of laboratory-confirmed SARS-CoV-2 infection on thyroid function tests (TFTs) in pregnant women and to evaluate whether TFT changes are related to the severity and prognosis. METHODS: Consecutive pregnant women tested for SARS-CoV-2 by RT-PCR at Ankara City Hospital were recruited between January 2021 and September 2021. Thyroid-stimulating hormone (TSH), free thyroxine (FT4) and free triiodothyronine (FT3), thyroid peroxidase antibody (anti-TPO), and thyroglobulin antibody (anti-TG) were measured on admission. RESULTS: Among 747 eligible pregnant women with the same baseline characteristics, 369 RT-PCR-positive women in the patient group and 378 RT-PCR-negative women in the control group were included in the analyses. Pregnant women in the patient group had significantly lower TSH, FT4, FT3, Anti TPO, and Anti TG concentrations compared with those in the control group (p < 0.001). The proportion of patient groups with mild, moderate, severe, and critical diseases were 297 (80.4%), 40 (10.8%), 17 (4.6%), and 15 (4.2%), respectively, among which with the moderate, severe, and critical disease had significantly lower FT3 values (2.5 vs 2.19 pg/mL, p < 0.001) and higher nonthyroidal illness syndrome (NTIS) (29.2 vs. 8.4%, p < 0.001) than those with mild disease. Lower FT3 values increased the risk of ICU admission, NICU admission, and severe disease (p < 0.001). FT3 and TSH correlated positively with lymphocytes (p < 0.001) and negatively correlated with C-reactive protein (CRP) (p < 0.001, p = 0.005). CONCLUSION: The SARS-CoV-2 infection seems to have an impact on the TFTs of pregnant women, and particularly FT3 level seems to be correlated with disease severity.

Heat shock protein amplification improves cerebellar myelination in the Npc1nih mouse model.

BACKGROUND: Niemann-Pick disease type C (NPC) is a rare prematurely fatal lysosomal lipid storage disease with limited therapeutic options. The prominent neuropathological hallmarks include hypomyelination and cerebellar atrophy. We previously demonstrated the efficacy of recombinant human heat shock protein 70 (rhHSP70) in preclinical models of the disease. It reduced glycosphingolipid levels in the central nervous system (CNS), improving cerebellar myelination and improved behavioural phenotypes in Npc1nih (Npc1-/-) mice. Furthermore, treatment with arimoclomol, a well-characterised HSP amplifier, attenuated lysosomal storage in NPC patient fibroblasts and improved neurological symptoms in Npc1-/- mice. Taken together, these findings prompted the investigation of the effects of HSP amplification on CNS myelination. METHODS: We administered bimoclomol daily or rhHSP70 6 times per week to Npc1-/- (BALB/cNctr-Npc1m1N/J, also named Npc1nih) mice by intraperitoneal injection from P7 through P34 to investigate the impact on CNS myelination. The Src-kinase inhibitor saracatinib was administered with/without bimoclomol twice daily to explore the contribution of Fyn kinase to bimoclomol's effects. FINDINGS: Treatment with either bimoclomol or rhHSP70 improved myelination and increased the numbers of mature oligodendrocytes (OLs) as well as the ratio of active-to-inactive forms of phosphorylated Fyn kinase in the cerebellum of Npc1-/- mice. Additionally, treatment with bimoclomol preserved cerebellar weight, an effect that was abrogated when co-administered with saracatinib, an inhibitor of Fyn kinase. Bimoclomol-treated mice also exhibited increased numbers of immature OLs within the cortex. INTERPRETATION: These data increase our understanding of the mechanisms by which HSP70 regulates myelination and provide further support for the clinical development of HSP-amplifying therapies in the treatment of NPC. FUNDING: Funding for this study was provided by Orphazyme A/S (Copenhagen, Denmark) and a Pathfinder Award from The Wellcome Trust.

Development of curcumin incorporated composite films based on chitin and glucan complexes extracted from Agaricus bisporus for active packaging of chicken breast meat.

Composite films were prepared by combining different concentrations of curcumin with chitin and glucan complexes (CGCs) extracted from Agaricus bisporus via a solution casting method. The developed curcumin doped CGC (CGC/Cu) films were characterized in terms of surface, optical, structural, barrier, mechanical, antioxidant, and antimicrobial properties. The biodegradability of CGC/Cu films was determined in soil for 14 days. The incorporation of curcumin significantly affected the surface morphology and improved light barrier properties, radical scavenging activity, and total phenolic content of the films. The CGC/Cu films containing different concentrations of curcumin showed antibacterial activity against Escherichia coli, while antibacterial activity against Staphylococcus aureus was not observed with the developed films. Afterward, the microbial properties of the fresh chicken breast were examined during refrigerated storage for 10 days. The shelf-life of chicken samples wrapped in the developed film was extended at least 40 % compared to the control sample. In conclusion, curcumin incorporated CGC based films can serve as a promising biodegradable active packaging material to improve the shelf-life of meat products.

Correction: Molecular basis for a new bovine model of Niemann-Pick type C disease.

[This corrects the article DOI: 10.1371/journal.pone.0238697.].

Acetyl-leucine slows disease progression in lysosomal storage disorders.

Acetyl-dl-leucine is a derivative of the branched chain amino acid leucine. In observational clinical studies, acetyl-dl-leucine improved symptoms of ataxia, in particular in patients with the lysosomal storage disorder, Niemann-Pick disease type C1. Here, we investigated acetyl-dl-leucine and its enantiomers acetyl-l-leucine and acetyl-d-leucine in symptomatic Npc1-/- mice and observed improvement in ataxia with both individual enantiomers and acetyl-dl-leucine. When acetyl-dl-leucine and acetyl-l-leucine were administered pre-symptomatically to Npc1-/- mice, both treatments delayed disease progression and extended life span, whereas acetyl-d-leucine did not. These data are consistent with acetyl-l-leucine being the neuroprotective enantiomer. Altered glucose and antioxidant metabolism were implicated as one of the potential mechanisms of action of the l-enantiomer in Npc1-/- mice. When the standard of care drug miglustat and acetyl-dl-leucine were used in combination significant synergy resulted. In agreement with these pre-clinical data, when Niemann-Pick disease type C1 patients were evaluated after 12 months of acetyl-dl-leucine treatment, rates of disease progression were slowed, with stabilization or improvement in multiple neurological domains. A beneficial effect of acetyl-dl-leucine on gait was also observed in this study in a mouse model of GM2 gangliosidosis (Sandhoff disease) and in Tay-Sachs and Sandhoff disease patients in individual-cases of off-label-use. Taken together, we have identified an unanticipated neuroprotective effect of acetyl-l-leucine and underlying mechanisms of action in lysosomal storage diseases, supporting its further evaluation in clinical trials in lysosomal disorders.

Effect of COVID-19 pandemic process on prenatal diagnostic procedures.

OBJECTIVE: To evaluate the accessibility of pregnant women to prenatal screening and diagnostic tests during the COVID-19 pandemic process and analyze the effect of the pandemic process on acceptance-rejection rates of fetal diagnostic procedures for high risk pregnancies. MATERIALS AND METHODS: As part of this cross-sectional study, during the pandemic, between the dates of 11 March 2020-30 June 2020 at Karadeniz Technical University Faculty of Medicine Perinatology Clinic, fetal structural anomaly detected by ultrasonography or with increased risk in screening test in the first and second trimester of high risk pregnancies, who were therefore recommended a prenatal diagnosis test, were defined as the control group and retrospectively compared with high risk pregnancies of the same periods (11 March 2019-30 June 2019) in the previous year. RESULTS: A total of 267 cases were evaluated within the scope of the study. The rate of pregnant women undergoing the first and second trimester screening tests was 83% in the control group and 56% for pregnant women in the study group. When the total number of prenatal diagnostic procedures and the year each of the procedures performed are compared, a statistically significant difference was found between the study and control groups (p: .041 and p < .001, respectively). When evaluating the rates of performed prenatal diagnostic procedures during the first patient visit in comparison to years, a statistically significant difference was observed in the A/S group and in the total number of cases (p = .023, p < .001, respectively). Similarly, the rate of performed prenatal diagnostic procedure during the first patient visit and the patient's city of residence was similarly statistically significant from year to year (p < .05). CONCLUSIONS: The decrease in number of prenatal diagnosis and screening tests during the COVID-19 pandemic draws attention. Prenatal care services are a serious issue that cannot be overcome by any deficiencies in both maternal and fetal care.

Molecular basis for a new bovine model of Niemann-Pick type C disease.

Niemann-Pick type C disease is a lysosomal storage disease affecting primarily the nervous system that results in premature death. Here we present the first report and investigation of Niemann-Pick type C disease in Australian Angus/Angus-cross calves. After a preliminary diagnosis of Niemann-Pick type C, samples from two affected calves and two obligate carriers were analysed using single nucleotide polymorphism genotyping and homozygosity mapping, and NPC1 was considered as a positional candidate gene. A likely causal missense variant on chromosome 24 in the NPC1 gene (NM_174758.2:c.2969C>G) was identified by Sanger sequencing of cDNA. SIFT analysis, protein alignment and protein modelling predicted the variant to be deleterious to protein function. Segregation of the variant with disease was confirmed in two additional affected calves and two obligate carrier dams. Genotyping of 403 animals from the original herd identified an estimated allele frequency of 3.5%. The Niemann-Pick type C phenotype was additionally confirmed via biochemical analysis of Lysotracker Green, cholesterol, sphingosine and glycosphingolipids in fibroblast cell cultures originating from two affected calves. The identification of a novel missense variant for Niemann-Pick type C disease in Angus/Angus-cross cattle will enable improved breeding and management of this disease in at-risk populations. The results from this study offer a unique opportunity to further the knowledge of human Niemann-Pick type C disease through the potential availability of a bovine model of disease.

Beneficial Effects of Acetyl-DL-Leucine (ADLL) in a Mouse Model of Sandhoff Disease.

Sandhoff disease is a rare neurodegenerative lysosomal storage disease associated with the storage of GM2 ganglioside in late endosomes/lysosomes. Here, we explored the efficacy of acetyl-DL-leucine (ADLL), which has been shown to improve ataxia in observational studies in patients with Niemann-Pick Type C1 and other cerebellar ataxias. We treated a mouse model of Sandhoff disease (Hexb-/-) (0.1 g/kg/day) from 3 weeks of age with this orally available drug. ADLL produced a modest but significant increase in life span, accompanied by improved motor function and reduced glycosphingolipid (GSL) storage in the forebrain and cerebellum, in particular GA2. ADLL was also found to normalize altered glucose and glutamate metabolism, as well as increasing autophagy and the reactive oxygen species (ROS) scavenger, superoxide dismutase (SOD1). Our findings provide new insights into metabolic abnormalities in Sandhoff disease, which could be targeted with new therapeutic approaches, including ADLL.

Mechanistic convergence and shared therapeutic targets in Niemann-Pick disease.

Niemann-Pick disease type C (NPC) and Tangier disease are genetically and clinically distinct rare inborn errors of metabolism. NPC is caused by defects in either NPC1 or NPC2; whereas Tangier disease is caused by a defect in ABCA1. Tangier disease is currently without therapy, whereas NPC can be treated with miglustat, a small molecule inhibitor of glycosphingolipid biosynthesis that slows the neurological course of the disease. When a Tangier disease patient was misdiagnosed with NPC and treated with miglustat, her symptoms improved. This prompted us to consider whether there is mechanistic convergence between these two apparently unrelated rare inherited metabolic diseases. In this study, we found that when ABCA1 is defective (Tangier disease) there is secondary inhibition of the NPC disease pathway, linking these two diseases at the level of cellular pathophysiology. In addition, this study further supports the hypothesis that miglustat, as well as other substrate reduction therapies, may be potential therapeutic agents for treating Tangier disease as fibroblasts from multiple Tangier patients were corrected by miglustat treatment.

Synthesis and Study of Multifunctional Cyclodextrin-Deferasirox Hybrids.

Metal dyshomeostasis is central to a number of disorders that result from, inter alia, oxidative stress, protein misfolding, and cholesterol dyshomeostasis. In this respect, metal deficiencies are usually readily corrected by treatment with supplements, whereas metal overload can be overcome by the use of metal-selective chelation therapy. Deferasirox, 4-[(3Z,5E)-3,5-bis(6-oxo-1-cyclohexa-2,4-dienylidene)-1,2,4-triazolidin-1-yl]benzoic acid, Exjade, or ICL670, is used clinically to treat hemosiderosis (iron overload), which often results from multiple blood transfusions. Cyclodextrins are cyclic glucose units that are extensively used in the pharmaceutical industry as formulating agents as well as for encapsulating hydrophobic molecules such as in the treatment of Niemann-Pick type C or for hypervitaminosis. We conjugated deferasirox, via an amide coupling reaction, to both 6A -amino-6A -deoxy-ß-cyclodextrin and 3A -amino-3A -deoxy-2A (S),3A (S)-ß-cyclodextrin, at the upper and lower rim, respectively, creating hybrid molecules with dual properties, capable of both metal chelation and cholesterol encapsulation. Our findings emphasize the importance of the conjugation of ß-cyclodextrin with deferasirox to significantly improve the biological properties and to decrease the cytotoxicity of this drug.

ß3-Adrenoceptor Control of Lower Genitourinary Tract Organs and Function in Male: An Overview.

The sympathetic nervous system is one component of the nervous regulatory system of the physiological function of the lower genitourinary tract. Our knowledge on the role of this sympathetic system has advanced during the last decade due to the characterization of ß3-adrenoceptors (ß3-ARs) in the urogenital system. This review focuses on the pharmacological and molecular evidence supporting the functional roles of ß3-AR in male genitourinary tissues of various species. An electronic search in two different databases was performed including MEDLINE (PubMed) and EMBASE from 2010 to 2016. ß3-agonists may be a promising alternative to antimuscarinics in the treatment of overactive bladder (OAB) based on available evidence. Although more recent studies have evaluated the involvement of ß3-ARs in the physiological control and regulation of various tissues of the lower genitourinary tract mainly urinary bladder, penis, urethra, ureter, there are few innovations in the pipe-line. Among the ß3-agonists, mirabegron is a unique drug licensed for the treatment of patients with OAB. Many drugs classified as ß3-agonists are still under investigations for the treatment of OAB, lower urinary tract symptoms, ureteral stones, benign prostate hyperplasia, prostate cancer and erectile dysfunction. This review discusses the potential roles of ß3-AR as new therapeutic targets by evaluating the results of preclinical and clinical studies related to male lower genitourinary tract function. Looking into the future, the potential benefits of ß3- AR agonists from experimental and clinical investigations may provide an attractive therapeutic option.

Aging and sexual health: getting to the problem.

Erectile dysfunction (ED) is one of the most common disorders in male and is often associated with other age-related comorbidities. The aging process affects the structural organization and function of penile erectile components such as smooth muscle cell and vascular architecture. These modifications affect penile hemodynamics by impairing cavernosal smooth muscle cell relaxation, reducing penile elasticity, compliance and promoting fibrosis. This review aims to identify the mechanisms of ED in the penile aging process in experimental and clinical data. It also highlights areas that are in need of more research. The search strategies yielded total records screened from PubMed. Clarification of the molecular mechanisms that accompanies corpus cavernosum aging and aging-associated ED will aid new perspectives in the development of novel mechanism-based therapeutic approaches. Age is not a limiting factor for ED medical management, and it is never too late to treat. Hypogonadism should be managed regardless of age, and synergistic effects have been found during testosterone (T) replacement therapy when used along with oral phosphodiesterase-5 (PDE-5) inhibitors. Therefore, the clinical management of ED related to aging can be done by therapeutic interventions that include PDE-5 inhibitors, and other pharmacological treatments.

Intracavernous Injection of Human Umbilical Cord Blood Mononuclear Cells Improves Erectile Dysfunction in Streptozotocin-Induced Diabetic Rats.

INTRODUCTION: Erectile dysfunction (ED) worsens in men with diabetes. Human umbilical cord blood (HUCB), because of its widespread availability and low immunogenicity, is a valuable source for stem cell-based therapies. AIM: To determine the effect of intracavernous injection of HUCB mononuclear cells (MNCs) on ED in rats with diabetes induced by streptozotocin. METHODS: Thirty adult male Sprague-Dawley rats were equally divided into three groups: (i) control, (ii) diabetes induced by streptozotocin (35 mg/kg intravenously for 8 weeks), and (iii) diabetic rats treated with MNCs (1 × 106 cells by intracavernosal injection). The HUCB-MNCs isolated by the Ficoll-Hypaque technique were obtained from eight healthy donors and administered to diabetic rats after 4 weeks. MAIN OUTCOME MEASURES: The ratio of intracavernosal pressure to mean arterial pressure ratio; the protein expression of endothelial and neuronal markers, such as von Willebrand factor, neuronal nitric oxide synthase, hypoxia-inducible factor-1α, and vascular endothelium growth factor; and the relative area of smooth muscle to collagen using western blotting and Masson trichrome staining were determined. RESULTS: Diabetic rats demonstrated a significantly decreased ratio of intracavernosal pressure to mean arterial pressure (0.26 ± 0.04; P < .01) and treatment with MNCs restored erectile function in diabetic rats (0.67 ± 0.05) compared with control rats (0.56 ± 0.02). In bath studies, neurogenic relaxant and contractile responses were significantly decreased in diabetic cavernosal tissues, which were restored by treatment. The ratio of smooth muscle to collagen was partly recovered by treatment, whereas von Willebrand factor levels were not altered in any group. Neuronal nitric oxide synthase and vascular endothelium growth factor levels were decreased, which were not restored by treatment. Increased hypoxia-inducible factor-1α protein expression in the diabetic group was completely normalized in MNC-treated diabetic samples. CONCLUSION: These results suggest that HUCB-MNC treatment can enhance the recovery of erectile function and promote numerous activities such the contribution of the hypoxia-inducible factor-1α and von Willebrand factor pathway to the neurogenic erectile response of diabetic rats. HUCB-MNCs in the healing process could involve an adaptive regenerative response and appear to be a potential candidate for cell-based therapy in ED of men with diabetes. It is evident that HUCB could provide a realistic therapeutic modality for the treatment of diabetic ED.