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1.
Spectrochim Acta A Mol Biomol Spectrosc ; 320: 124644, 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38901235

ABSTRACT

Reaction between the polymeric [RuCl2(CO)2]n and the N,N-bidentate ligand, 8-amino-quinoline (Quin), in methanol, afforded the photoactivated CO releasing molecule with the formula of trans-(Cl,Cl)-[RuCl2(CO)2Quin]. In the presence of biomolecules or in solvents with varying polarity and coordinating abilities, the solvatochromic characteristics and dark stability were investigated. A new board band emerged in the visible spectrum during the illumination, and its position varies according to the type of solvent used, indicating the role of the solvent in controlling the nature of the CO-depleted species. Spectral methods were used in combination with density functional theory simulations to get insight into the local minimum structure and the electronic properties of the Ru(II) complex. The results of the myoglobin assay showed that within the first two hours of illumination, one of the two CO molecules was released. The cytotoxic properties of the Ru(II)-based complex were investigated against normal mice bone marrow stromal cells and malignant human acute monocytic leukaemia cells.

2.
Eur J Pharmacol ; 971: 176525, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38561101

ABSTRACT

Depression is a debilitating mental disease that negatively impacts individuals' lives and society. Novel hypotheses have been recently proposed to improve our understanding of depression pathogenesis. Impaired neuroplasticity and upregulated neuro-inflammation add-on to the disturbance in monoamine neurotransmitters and therefore require novel anti-depressants to target them simultaneously. Recent reports demonstrate the antidepressant effect of the anti-diabetic drug liraglutide. Similarly, the natural flavonoid naringenin has shown both anti-diabetic and anti-depressant effects. However, the neuro-pharmacological mechanisms underlying their actions remain understudied. The study aims to evaluate the antidepressant effects and neuroprotective mechanisms of liraglutide, naringenin or a combination of both. Depression was induced in mice by administering dexamethasone (32 mcg/kg) for seven consecutive days. Liraglutide (200 mcg/kg), naringenin (50 mg/kg) and a combination of both were administered either simultaneously or after induction of depression for twenty-eight days. Behavioral and molecular assays were used to assess the progression of depressive symptoms and biomarkers. Liraglutide and naringenin alone or in combination alleviated the depressive behavior in mice, manifested by decrease in anxiety, anhedonia, and despair. Mechanistically, liraglutide and naringenin improved neurogenesis, decreased neuroinflammation and comparably restored the monoamines levels to that of the reference drug escitalopram. The drugs protected mice from developing depression when given simultaneously with dexamethasone. Collectively, the results highlight the usability of liraglutide and naringenin in the treatment of depression in mice and emphasize the different pathways that contribute to the pathogenesis of depression.


Subject(s)
Depression , Flavanones , Liraglutide , Mice , Animals , Depression/metabolism , Liraglutide/pharmacology , Liraglutide/therapeutic use , Antidepressive Agents/pharmacology , Antidepressive Agents/therapeutic use , Inflammation/drug therapy , Neurogenesis , Dexamethasone/pharmacology
3.
Metabolites ; 14(4)2024 Apr 06.
Article in English | MEDLINE | ID: mdl-38668336

ABSTRACT

The Asian Indian Beta Cell function (ABCs) in Infants Study examined the associations of maternal weight on infant pancreatic beta cell function across 7 months postpartum. Pregnant women aged 18-35 years were recruited in Hyderabad, India. Women were classified by first trimester weight as underweight (UW), BMI < 18.5 kg/m2; normal weight (NW), BMI 18.5-22.9 kg/m2; or overweight (OW), BMI 23.0 through <28.5 kg/m2. At age > 7 months, infants had an oral glucose tolerance test (OGTT, 1.75 g glucose/kg bodyweight) following a 3 h fast. Infant blood samples were assayed for C-peptide and glucose. Infant beta cell function (HOMA2-B; disposition index, DI) and insulin resistance (HOMA2-IR) were compared across maternal weight groups. Mothers (UW n = 63; NW n = 43; OW n = 29) had similar age at delivery and second trimester 50 g glucose challenge test results. Cord HOMA2-B values were 51% greater for IUW (83.5, SD 55.2) and 44% greater for IOW (79.9, SD 60.8) vs. INW (55.4, SD 51.5), forming a U-shaped relationship between maternal weight and HOMA2-B. No qualitative differences in HOMA2-IR were found at birth. However, at 7 months postpartum, HOMA2-IR changed most within IUW (-64% median reduction) and changed the least in IOW (-7% median reduction). At seven months postpartum, DI was higher in IUW vs. the other groups (geometric mean IUW 1.9 SD 2.5; INW 1.3 SD 2.6 or vs. IOW mean 1.2 SD 3.7), reflecting a +49% difference in DI. Evidence from this study illustrates adaptations in the pancreatic functional response of infants associated with the maternal nutritional environment.

4.
Sci Rep ; 14(1): 3096, 2024 02 07.
Article in English | MEDLINE | ID: mdl-38326395

ABSTRACT

A single injection of platelet-rich plasma (PRP) or stromal vascular fraction (SVF) in treating neurological ailments suggests promise; however, there is limited evidence of the efficacy of combination therapy. This trial aimed to determine whether combining SVF and PRP could provide further therapeutic effects in treating multiple sclerosis (MS). Fifteen Persian cats were separated into three groups (n = 5): group I (control negative), and group II (control positive); EB was injected intrathecally into the spinal cord and then treated 14 days later with intrathecal phosphate buffered saline injection, and group III (SVF + PRP), cats were injected intrathecally with EB through the spinal cord, followed by a combination of SVF and PRP 14 days after induction. Therapeutic effects were evaluated using the Basso-Beattie-Bresnahan scale throughout the treatment timeline and at the end. Together with morphological, MRI scan, immunohistochemical, transmission electron microscopy, and gene expression investigations. The results demonstrated that combining SVF and PRP successfully reduced lesion intensity on gross inspection and MRI. In addition to increased immunoreactivity to Olig2 and MBP and decreased immunoreactivity to Bax and GFAP, there was a significant improvement in BBB scores and an increase in neurotrophic factor (BDNF, NGF, and SDF) expression when compared to the positive control group. Finally, intrathecal SVF + PRP is the most promising and safe therapy for multiple sclerosis, resulting in clinical advantages such as functional recovery, MRI enhancement, and axonal remyelination.


Subject(s)
Multiple Sclerosis , Platelet-Rich Plasma , Spinal Cord Injuries , Animals , Cats , bcl-2-Associated X Protein , Stromal Vascular Fraction , Sclerosis , Nerve Growth Factors
5.
Pharmaceutics ; 16(2)2024 Feb 14.
Article in English | MEDLINE | ID: mdl-38399322

ABSTRACT

In the present study, we sought to develop materials applicable to personal and collective protection equipment to mitigate SARS-CoV-2. For this purpose, AgNPs were synthesized and stabilized into electrospinning nanofiber matrices (NMs) consisting of poly(vinyl alcohol) (PVA), chitosan (CHT), and poly-ε-caprolactone (PCL). Uniaxial nanofibers of PVA and PVA/CHT were developed, as well as coaxial nanofibers of PCL[PVA/CHT], in which the PCL works as a shell and the blend as a core. A crucial aspect of the present study is the in situ synthesis of AgNPs using PVA as a reducing and stabilizing agent. This process presents few steps, no additional toxic reducing agents, and avoids the postloading of drugs or the posttreatment of NM use. In general, the in situ synthesized AgNPs had an average size of 11.6 nm, and the incorporated nanofibers had a diameter in the range of 300 nm, with high uniformity and low polydispersity. The NM's spectroscopic, thermal, and mechanical properties were appropriate for the intended application. Uniaxial (PVA/AgNPs and PVA/CHT/AgNPs) and coaxial (PCL[PVA/CHT/AgNPs]) NMs presented virucidal activity (log's reduction ≥ 5) against mouse hepatitis virus (MHV-3) genus Betacoronavirus strains. In addition to that, the NMs did not present cytotoxicity against fibroblast cells (L929 ATCC® CCL-1TM lineage).

6.
BMC Vet Res ; 19(1): 260, 2023 Dec 06.
Article in English | MEDLINE | ID: mdl-38057858

ABSTRACT

The portio-vaginalis uteri (PVU) and its mucus secretion have shown an essential role in conception. A significant endeavour to improve buffaloes' reproductive efficiency is the investigation of their basic reproductive pattern, which provides a reference for applications in breeding and pregnancy. The present study aimed to evaluate the anatomical and histological alterations in PVU regarding to the vaginal artery (VA) hemodynamic at luteal and early pregnant stages in buffalos. Egyptian live buffaloes (n = 16) and fresh genitals (n = 25) of mature buffalo were used. Different luteal and early pregnant stages were macroscopically identified with the shape and mucosal colouration with discharges of the PVU. Histological examination showed a significant difference in area % of alcian blue and periodic acid Schiff positive granules which considered an indication for presence of acidic and neutral mucins respectively in the epithelial cells of PVU mucosa which increased in pregnant stage than in other luteal stages. VA assessment demonstrated an increase in luminal diameter and thickness of tunica muscularis in pregnant stage than other stages (P < 0.05). Middle uterine (MUA) and VA arteries peak velocity point (PSV mm/sec) were elevated (P < 0.05) in pregnant stage, with a marked reduction in both resistance and pulsatility indices (RI and PI), and ratio of systolic /diastolic (S/D). Positive correlation was detected between VA. PSV and, MUA. PSV (r = 0.87), but a negative relation was detected with VA. S/D (r = -0.77), VA.PI (r = -0.89), VA. RI (r = -0.97), MUA. S/D (r = -0.94), MUA. PI (r = -0.85), and MUA. RI (r = -0.88). Doppler indices were negatively corrected with the VA. PSV (r = -0.68). It was concluded that there was a significant alterations in histological features of the cervical PVU at different physiological stages (luteal and early pregnant) in buffalos in relation to the MUA and VA hemodynamic pattern and that hypotheses can be established regarding the female cyclicity that affected by both arteries hemodynamics change.


Subject(s)
Bison , Buffaloes , Pregnancy , Female , Animals , Buffaloes/physiology , Lutein , Uterus , Reproduction , Arteries , Blood Flow Velocity
7.
Cureus ; 15(11): e48820, 2023 Nov.
Article in English | MEDLINE | ID: mdl-38106702

ABSTRACT

Background The objective of this cross-sectional study is to identify the prevalence of contraceptive use and the knowledge and attitudes of Saudi women towards it. Methods We distributed a survey to Saudi women aged 19-49 attending primary care centers under King Abdulaziz Medical City in Riyadh to identify their views on using contraceptives and what they know about them. We calculated the sample size using the Roasoft sample calculator. Results This study enrolled 432 Saudi women. The number of women who were contraceptive users was 249 (57.6%). Among those who were using contraceptives, the most common reason was the idea of taking care of themselves and avoiding consecutive pregnancies (105, 42.2%). Of the non-users, the most common reason was concerns regarding side effects (41%). The most commonly used contraceptive methods were contraceptive pills (55.6%) and intrauterine devices (IUDs) (17.6%). The most commonly used non-pharmacological contraception methods were withdrawal (17.6%) and rhythm (8.6%). Conclusion In this study, factors associated with contraceptive use among Saudi women were explored. Demographic data, type, attitude, and associations provided insight into factors taken into consideration while developing future contraceptives in addition to improving clinical practice.

8.
Cureus ; 15(9): e44859, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37809273

ABSTRACT

Objectives The aim of the study is to measure the prevalence of suicidal ideation among nurses at King Saud University Medical City, compare its prevalence between male and female nurses, and identify the potential risk factors. Methods We conducted a cross-sectional study. The questionnaire was distributed to nurses via email. It consisted of demographics, Depression, Anxiety and Stress Scale (DASS21), and Suicidal Ideation Scale (SIS). We used the Statistical Package for the Social Sciences (SPSS) statistical software for analysis. Results The total number of participants was 419. The estimated prevalence of suicidal ideation among nurses was 24.58%. The prevalence among female and male nurses was 24.67% and 23.68%, respectively. Moreover, we found that nurses who are non-Muslim, single, and living by themselves are highly correlated with suicidal ideation. Depression, stress, and anxiety are also significantly associated with suicidality, with depression being the most significantly related to suicidal ideation. Conclusion Nurses who experienced depression, anxiety, and stress had an increased likelihood of suicidal ideation. This study demonstrates the need to raise awareness of depression, anxiety, and stress in order to prevent suicidal ideation among nurses. Further research is needed to develop measures of successful monitoring and prevention.

10.
Cureus ; 15(6): e40995, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37503490

ABSTRACT

BACKGROUND: Guillain-Barré Syndrome (GBS) is the most common cause of acute, usually post-infectious, peripheral neuropathy resulting in a symmetrical, ascending paralysis. We evaluated the clinical and neurophysiological features, treatment, and outcomes of patients with GBS in our center. METHODS: A retrospective chart review on patients with GBS admitted to King Abdulaziz Medical City, Riyadh, Saudi Arabia, from January 2011 to December 2020. Data were analyzed using JMP statistical software version 15 pro. RESULTS: A total of 86 patients who met the criteria were included, 55 (64%) were males, with a mean age of 49.5+/-17.5 years. Antecedent infection was reported in 53 (61.6%), 51 (62.2%) presented within one week of symptoms onset. Ascending weakness was seen in 55 (70.5%), while 70 (81.4%) had areflexia. Acute motor axonal neuropathy (AMAN) was the commonest electrophysiological type of GBS in 41 (51.9%) patients. Albuminocytologic dissociation was seen in 48 (57%) who had lumbar puncture. Nearly half, 41 (47.7%) were admitted to the intensive care unit (ICU). Seventy (81.3%) were treated with intravenous immunoglobulin. There was no significant difference in the clinical presentation, management, ICU requirement, and discharge disposition between males and females. Females were more likely to have a higher disability at discharge (p=0.01). Patients younger than 60 years were more likely to require ICU admission (p=<0.01). CONCLUSION: Our patients with GBS were slightly older than previously reported from the region. AMAN was the commonest type of GBS. Younger patients were more likely to need ICU admission, whereas females were more likely to have a more severe disability.

11.
ESMO Open ; 8(3): 101569, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37285716

ABSTRACT

BACKGROUND: REGOBONE multicohort study explored the efficacy and safety of regorafenib for patients with advanced bone sarcomas; this report details the cohort of patients with relapsed advanced or metastatic chordoma. METHODS: Patients with relapsed chordoma progressing despite 0-2 prior lines of systemic therapy, were randomised (2 : 1) to receive regorafenib (160 mg/day, 21/28 days) or placebo. Patients on placebo could cross over to receive regorafenib after centrally-confirmed progression. The primary endpoint was the progression-free rate at 6 months (PFR-6) (by RECIST 1.1). With one-sided α of 0.05, and 80% power, at least 10/24 progression-free patients at 6 months (PFR-6) were needed for success. RESULTS: From March 2016 to February 2020, 27 patients were enrolled. A total of 23 patients were assessable for efficacy: 7 on placebo, 16 on regorafenib, 16 were men, median age was 66 (32-85) years. At 6 months, in the regorafenib arm, 1 patient was not assessable, 6/14 were non-progressive (PFR-6: 42.9%; one-sided 95% CI = 20.6) 3/14 discontinued regorafenib due to toxicity; and in the placebo arm, 2/5 patients were non-progressive (PFR-6: 40.0%; one-sided 95% CI = 7.6), 2 were non-assessable. Median progression-free survival was 8.2 months (95% CI 4.5-12.9 months) on regorafenib and 10.1 months (95% CI 0.8 months-non evaluable [NE]) on placebo. Median overall survival rates were 28.3 months (95% CI 14.8 months-NE) on regorafenib but not reached in placebo arm. Four placebo patients crossed over to receive regorafenib after centrally-confirmed progression. The most common grade ≥3 regorafenib-related adverse events were hand-foot skin reaction (22%), hypertension (22%), pain (22%), and diarrhoea (17%), with no toxic death. CONCLUSION: This study failed to show any signal of benefit for regorafenib in patients with advanced/metastatic recurrent chordoma.


Subject(s)
Chordoma , Male , Humans , Aged , Female , Chordoma/drug therapy , Chordoma/chemically induced , Phenylurea Compounds/adverse effects , Pyridines/pharmacology , Pyridines/therapeutic use , Progression-Free Survival
12.
J Indian Inst Sci ; : 1-22, 2023 Mar 21.
Article in English | MEDLINE | ID: mdl-37362852

ABSTRACT

Indian people are at high risk for type 2 diabetes (T2DM) even at younger ages and lower body weights. Already 74 million people in India have the disease, and the proportion of those with T2DM is increasing across all strata of society. Unique aspects, related to lower insulin secretion or function, and higher hepatic fat deposition, accompanied by the rise in overweight (related to lifestyle changes) may all be responsible for this unrelenting epidemic of T2DM. Yet, research to understand the causes, pathophysiology, phenotypes, prevention, treatment, and healthcare delivery of T2DM in India seriously lags behind. There are major opportunities for scientific discovery and technological innovation, which if tapped can generate solutions for T2DM relevant to the country's context and make leading contributions to global science. We analyze the situation of T2DM in India, and present a four-pillar (etiology, precision medicine, implementation research, and health policy) strategic research framework to tackle the challenge. We offer key research questions for each pillar, and identify infrastructure needs. India offers a fertile environment for shifting the paradigm from imprecise late-stage diabetes treatment toward early-stage precision prevention and care. Investing in and leveraging academic and technological infrastructures, across the disciplines of science, engineering, and medicine, can accelerate progress toward a diabetes-free nation.

13.
Am J Clin Nutr ; 117(1): 175-181, 2023 01.
Article in English | MEDLINE | ID: mdl-36789936

ABSTRACT

BACKGROUND: It is unclear whether 25(OH)D concentrations in children and female adults may be influenced by inflammation and thus require adjustment when estimating the population prevalence of vitamin D deficiency. OBJECTIVES: We examined correlations between inflammation biomarkers, CRP or alpha-1-acid glycoprotein (AGP), and serum 25(OH)D concentrations among preschool children (PSC; 6-59 mo) and nonpregnant females of reproductive age (FRA; 15-49 y). METHODS: We analyzed cross-sectional data from 6 nationally representative nutrition surveys (Afghanistan, Cambodia, Pakistan, UK, USA, and Vietnam) conducted among PSC (n = 9880) and FRA (n = 14,749) from the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia project. Rank correlations between CRP or AGP and 25(OH)D concentrations were examined while taking into account complex survey design effects. RESULTS: Among both PSC and FRA, correlations between inflammation and vitamin D biomarkers were weak and inconsistent across surveys. For PSC, correlation coefficients between CRP and 25(OH)D concentrations ranged from -0.04 to 0.08, and correlations between AGP and 25(OH)D ranged from 0.01 to 0.05. Correlation coefficients between CRP and 25(OH)D for FRA ranged from -0.11 to 0.14, and correlations between AGP and 25(OH)D concentrations ranged from -0.05 to 0.01. CONCLUSIONS: Based on the weak and inconsistent correlations between CRP or AGP and 25(OH)D, there is no rationale to adjust for these inflammation biomarkers when estimating population prevalence of vitamin D deficiency in PSC or FRA.


Subject(s)
Anemia, Iron-Deficiency , Anemia , Vitamin D Deficiency , Adult , Child, Preschool , Female , Humans , Anemia/epidemiology , Biomarkers , C-Reactive Protein/analysis , Cross-Sectional Studies , Inflammation , Nutritional Status , Vitamin D , Vitamin D Deficiency/epidemiology , Vitamins , Adolescent , Young Adult , Middle Aged
14.
Stem Cell Res Ther ; 14(1): 6, 2023 01 11.
Article in English | MEDLINE | ID: mdl-36627662

ABSTRACT

BACKGROUND: Multiple sclerosis (MS) is the most frequent non-traumatic neurological debilitating disease among young adults with no cure. Over recent decades, efforts to treat neurodegenerative diseases have shifted to regenerative cell therapy. Adipose tissue-derived stromal vascular fraction (SVF) comprises a heterogeneous cell population, considered an easily accessible source of MSCs with therapeutic potential in autoimmune diseases. This study aimed to assess the regenerative capacity of low-level laser-activated SVF in an MS cat model. METHODS: Fifteen adult Persian cats were used in this study: Group I (control negative group, normal cats), Group II (EB-treated group, induced for MS by ethidium bromide (EB) intrathecal injection), and Group III (SVF co-treated group, induced for MS then treated with SVF on day 14 post-induction). The SVF was obtained after digesting the adipose tissue with collagenase type I and injecting it intrathecal through the foramen magnum. RESULTS: The results showed that the pelvic limb's weight-bearing locomotion activity was significantly (P ≤ 0.05) recovered in Group III, and the Basso, Beattie, and Bresnahan (BBB) scores of hindlimb locomotion were significantly higher in Group III (14 ± 0.44) than Group II (4 ± 0.31). The lesion's extent and intensity were reduced in the magnetic resonance imaging (MRI) of Group III. Besides, the same group showed a significant increase in the expression of neurotrophic factors: BDNF, SDF and NGF (0.61 ± 0.01, 0.51 ± 0.01 and 0.67 ± 0.01, respectively) compared with Group II (0.33 ± 0.01, 0.36 ± 0.006 and 0.2 ± 0.01, respectively). Furthermore, SVF co-treated group revealed a significant (P ≤ 0.05) increase in oligodendrocyte transcription factor (Olig2) and myelin basic protein (4 ± 0.35 and 6 ± 0.45, respectively) that was decreased in group II (1.8 ± 0.22 and 2.9 ± 0.20, respectively). Moreover, group III showed a significant (P ≤ 0.05) reduction in Bax and glial fibrillary acidic protein (4 ± 0.53 and 3.8 ± 0.52, respectively) as compared with group II (10.7 ± 0.49 and 8.7 ± 0.78, respectively). The transmission electron microscopy demonstrated regular more compact, and markedly (P ≤ 0.05) thicker myelin sheaths (mm) in Group III (0.3 ± 0.006) as compared with group II (0.1 ± 0.004). Based on our results, the SVF co-treated group revealed remyelination and regeneration capacity with a reduction in apoptosis and axonal degeneration. CONCLUSION: SVF is considered an easy, valuable, and promising therapeutic approach for treating spinal cord injuries, particularly MS.


Subject(s)
Multiple Sclerosis , Spinal Cord Injuries , Cats , Animals , Multiple Sclerosis/therapy , Stromal Vascular Fraction , Spinal Cord Injuries/therapy , Adipose Tissue , Stromal Cells
16.
Sci Rep ; 12(1): 18663, 2022 11 04.
Article in English | MEDLINE | ID: mdl-36333377

ABSTRACT

Pediatric liver transplantation rejection affects 20% of children. Currently, liver biopsy, expensive and invasive, is the best method of diagnosis. Discovery and validation of clinical biomarkers from blood or other biospecimens would improve clinical care. For this study, stored plasma samples were utilized from two cross-sectional cohorts of liver transplant patients at Children's Healthcare of Atlanta. High resolution metabolic profiling was completed using established methods. Children with (n = 18) or without (n = 25) acute cellular rejection were included in the analysis (n = 43 total). The mean age of these racially diverse cohorts ranged from 12.6 years in the rejection group and 13.6 years in the no rejection group. Linear regression provided 510 significantly differentiating metabolites between groups, and OPLS-DA showed 145 metabolites with VIP > 2. A total of 95 overlapping significant metabolites between OPLS-DA and linear regression analyses were detected. Pathway analysis (p < 0.05) showed bile acid biosynthesis and tryptophan metabolism as the top two differentiating pathways. Network analysis also identified tryptophan and clustered with liver enzymes and steroid use. We conclude metabolic profiling of plasma from children with acute liver transplant rejection demonstrates > 500 significant metabolites. This result suggests that development of a non-invasive biomarker-based test is possible for rejection screening.


Subject(s)
Graft Rejection , Liver Transplantation , Humans , Child , Graft Rejection/pathology , Cross-Sectional Studies , Tryptophan , Metabolomics/methods , Liver/pathology , Biomarkers , Postoperative Complications/pathology
17.
Inflamm Regen ; 42(1): 45, 2022 Oct 14.
Article in English | MEDLINE | ID: mdl-36229845

ABSTRACT

BACKGROUND: Multiple sclerosis (MS) is a progressive autoimmune demyelinating disease of the central nervous system. To date, there is no effective therapy for it. Our study aimed to determine the potential role of platelet-rich plasma (PRP) in the treatment of MS in cats. METHODS: The current study was conducted on 15 adult Persian cats that were divided into three groups: control negative, control positive (ethidium bromide (EB)-treated group), and PRP co-treated group (EB-treated group intrathecally injected with PRP on day 14 post-spinal cord injury). PRP was obtained by centrifuging blood on anticoagulant citrate dextrose and activating it with red and green laser diodes. The Basso-Beattie-Bresnahan (BBB) scores were used to assess the motor function recovery on days 1, 3, 7, 14, 20, and 28 following 14 days from EB injection. Moreover, magnetic resonance imaging (MRI) analysis, histopathological investigations, transmission electron microscopy (TEM) studies, and immunohistochemical analysis were conducted, and the gene expressions of nerve growth factors (NGFs), brain-derived neurotrophic factors (BDNF), and stromal cell-derived factors (SDF) were evaluated. RESULTS: Our results indicated that PRP had a significant ameliorative effect on the motor function of the hindlimbs as early as day 20 and so on. MRI revealed that the size and intensity of the lesion were significantly reduced in the PRP co-treated group. The histopathological and TEM investigations demonstrated that the PRP co-treated group had a significant improvement in the structure and organization of the white matter, as well as a high remyelination capacity. Furthermore, a significant increase in myelin basic protein and Olig2 immunoreactivity as well as a reduction in Bax and glial fibrillar acidic protein immune markers was observed. NGFs were found to be upregulated by gene expression. CONCLUSION: As a result, we concluded that the intrathecal injection of PRP was an effective, safe, and promising method for the treatment of MS.

18.
J Infect Dis ; 227(1): 50-60, 2022 12 28.
Article in English | MEDLINE | ID: mdl-36281651

ABSTRACT

BACKGROUND: Respiratory syncytial virus (RSV) is a leading viral respiratory pathogen in infants. The objective of this study was to generate RSV live-attenuated vaccine (LAV) candidates by removing the G-protein mucin domains to attenuate viral replication while retaining immunogenicity through deshielding of surface epitopes. METHODS: Two LAV candidates were generated from recombinant RSV A2-line19F by deletion of the G-protein mucin domains (A2-line19F-G155) or deletion of the G-protein mucin and transmembrane domains (A2-line19F-G155S). Vaccine attenuation was measured in BALB/c mouse lungs by fluorescent focus unit (FFU) assays and real-time polymerase chain reaction (RT-PCR). Immunogenicity was determined by measuring serum binding and neutralizing antibodies in mice following prime/boost on days 28 and 59. Efficacy was determined by measuring RSV lung viral loads on day 4 postchallenge. RESULTS: Both LAVs were undetectable in mouse lungs by FFU assay and elicited similar neutralizing antibody titers compared to A2-line19F on days 28 and 59. Following RSV challenge, vaccinated mice showed no detectable RSV in the lungs by FFU assay and a significant reduction in RSV RNA in the lungs by RT-PCR of 560-fold for A2-line19F-G155 and 604-fold for A2-line19F-G155S compared to RSV-challenged, unvaccinated mice. CONCLUSIONS: Removal of the G-protein mucin domains produced RSV LAV candidates that were highly attenuated with retained immunogenicity.


Subject(s)
Respiratory Syncytial Virus Infections , Respiratory Syncytial Virus Vaccines , Respiratory Syncytial Virus, Human , Animals , Mice , Vaccines, Attenuated , Mucins , Mice, Inbred BALB C , Respiratory Syncytial Virus, Human/genetics , Antibodies, Neutralizing , GTP-Binding Proteins , Antibodies, Viral , Viral Fusion Proteins/genetics
19.
Front Vet Sci ; 9: 896581, 2022.
Article in English | MEDLINE | ID: mdl-35982929

ABSTRACT

This study aims to compare the complete growth and development of corpus luteum (CL) in domestic buffalos from day 5 until day 40 after ovulation either in pregnant or non-pregnant animals and whether luteal vascularity (LV) with progesterone (P4) and nitric oxide (NO) could determine luteal functionality or not. Pluriparous buffalos (Bubalus bubalis) were categorized as pregnant (n = 6) or non-pregnant (n = 9) after pregnancy check at day 25. Animals were subjected to ultrasound analysis to determine the CL area (cm2) and LV. Blood sampling was performed following the Doppler examination. Ovarian tissue samples from non-pregnant buffalo genitalia (n = 18) and early pregnant buffalo genitalia (n = 3) were collected from great abattoirs. Luteal Doppler indices were lower in the pregnant group, while peak systolic velocity (PSV) was increased (p < 0.05) in the same pregnant females. Both P4 and NOMs were elevated (p < 0.05) in the pregnant group. There was a positive correlation (p < 0.01) between P4 and CL PSV. Based on our macroscopical examination, the CL of non-pregnant buffalos was classified into four stages. Histologically, stage I showed that CL was covered by a highly vascularized connective tissue (CT) capsule. It consisted of small and large lutein cells, whereas stage II was similar to stage I except for the presence of numerous fibroblast cells and vacuolated cells. Stage III was characterized by increasing the number of collagen fibers and the thickness of the blood vessels. Stage IV revealed thickening of the CT capsule and septae, regressed capillaries and arterioles, in addition to shrunken degenerated lutein cells. CL of pregnant buffalos revealed the same structure as CL at stage II. CL area was increased in the pregnant group. The collective data suggested that evaluation of the luteal artery could be extremely helpful to determine the potential benefits of colored and pulsed Doppler in CL vascularization assessment in both luteal and early pregnancy phases.

20.
BMC Vet Res ; 18(1): 301, 2022 Aug 04.
Article in English | MEDLINE | ID: mdl-35927671

ABSTRACT

Understanding the does reproductive hemodynamic changes during the estrous cycle is crucial for improving reproductive competence and fertility potential in this species. The objective of this study is to investigate the hemodynamic variations in ovarian (OA) and uterine (UA) arteries, histological and morphometric changes in ovarian and uterine tissues throughout the follicular (FP) and luteal (LP) phases in rabbits and determine estrogen (ER), progesterone (PR) receptors, and vascular endothelial growth factor (VEGF) distributions using immunohistochemistry.Fourteen adults pluriparous New Zealand rabbits were divided into rabbits at the FP (Day - 1; n = 7) and those at the LP (Day 9; n = 7). Animals were subjected to Doppler, hormonal (estrogen [E2], progesterone [P4], insulin-like growth factor [ILGF], and VEGF), histological, and immunohistochemical analyses. In LP, OA Doppler indices were significantly increased, whereas peak systolic velocity (PSV) was decreased compared with that in FP. UA Doppler indices were significantly decreased in the LP, whereas PSV was increased (P < 0.05). E2 levels were increased in the FP, whereas P4 levels were increased in the LP. The morphometric analysis of uterine tissues during the LP revealed an increase in the mean uterine endometrium length, endometrial connective tissue area percentage (%), endometrial glands number, myometrial area (%) and thickness. Furthermore, ovarian follicles and corpus luteum (CL) displayed strong positive immunoreactivity for ER, PR, and VEGF-A during both phases. The ovarian sections displayed a substantial (P < 0.05) increase in the area % of VEGF-A in the ovarian follicles during FP while in the CL during LP. Conversely, area percentage of VEGF-A immunoreactivity in the uterine luminal and glandular epithelia during the FP and LP revealed no differences. However, the number of VEGF-A-stained blood capillaries revealed an increase during LP than FP. In conclusion, this study demonstrated for the first time the changes in both ovarian and uterine arteries during two different phases of the rabbit cycle in relation to the histo-morphometric analysis and distribution of ER, PR, and VEGF-A, which regulate uterine functions that play a role in reproduction.


Subject(s)
Progesterone , Vascular Endothelial Growth Factor A , Animals , Corpus Luteum/diagnostic imaging , Corpus Luteum/metabolism , Estrogens , Female , Perfusion/veterinary , Rabbits , Vascular Endothelial Growth Factor A/metabolism
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