Cardiac stem cells: Current knowledge and future prospects

Regenerative medicine is the field concerned with the repair and restoration of the integrity of damaged human tissues as well as whole organs.Since the inception of the field several decades ago,regenerative medicine therapies,namely stem cells,have received significant attention in preclinical studies and clinical trials.Apart from their known potential for differentiation into the various body cells,stem cells enhance the organ's intrinsic regenerative capacity by altering its environment,whether by exogenous injection or introducing their products that modulate endogenous stem cell function and fate for the sake of regeneration.Recently,research in cardiology has highlighted the evidence for the existence of cardiac stem and progenitor cells(CSCs/CPCs).The global burden of cardiovascular diseases’morbidity and mortality has demanded an in-depth understanding of the biology of CSCs/CPCs aiming at improving the outcome for an innovative therapeutic strategy.This review will discuss the nature of each of the CSCs/CPCs,their environment,their interplay with other cells,and their metabolism.In addition,important issues are tackled concerning the potency of CSCs/CPCs in relation to their secretome for mediating the ability to influence other cells.Moreover,the review will throw the light on the clinical trials and the preclinical studies using CSCs/CPCs and combined therapy for cardiac regeneration.Finally,the novel role of nanotechnology in cardiac regeneration will be explored.     

Investigation of many bacterial and viral infections circulating in pigeons showing nervous symptoms

Pigeon’s flocks have shown several neurological symptoms including circling, torticollis, tremors, paralysis, which caused suspicion for viral or bacterial natural infections. Pigeon paramyxovirus type-1 (PPMV-1) is a notifiable disease-causing high morbidity and mortality with severe nervous symptoms. Clinical represented tissue specimens were collected from 50 infected pigeon flocks in eight governorates. All samples were examined bacteriologically (isolation, identification and serotyping) for E. coli, Salmonella spp., S. aureus and pseudomonas aeruginosa. Antimicrobial susceptibility test (AST) was accomplished for all isolates using a disk-diffusion test. For viral identification, RT-PCR specific oligonucleotide primers were used for distinguishing of Avian influenza virus, PPMV-1 and PPMV-3. Neurological manifestations were observed in pigeon’s flocks mainly in winter and autumn. The mortality rate in eight governorates was about 50% in 10 flocks and other houses mortality rate was ranged from 10 to 20%. Post mortem examination have shown hemorrhagic enteritis, soft and friable brain tissues and/or hemorrhages. The percentage of isolated bacteria E. coli, Salmonella spp., S. aureus and Pseudomonas aeruginosa were 75%, 75%, 50% and 18.75%; respectively. The antibiotic resistance pattern for bacterial isolates showed resist to ampicillin, amoxicillin- clavulinic acid, teteracyclin, ceftriaxone, doxycycline, sulfamethoxazole-trimethoprim and ceftazidine with different result for each type of bacteria, while Salmonella spp., isolates showed only a highly intermediate result for ciprofloxacin. Eight samples are positive with 16% to PPMV-1. Also, sample No.5,6,9 was co-infected with different types of bacterial isolates in addition to NDV. In conclusion, we reported several neurological symptoms in pigeon’s flocks mainly of bacterial infections (E. coli, Salmonella spp., S. aureus and Pseudomonas aeruginosa).     

Key dimer interface residues impact the catalytic activity of 3CLpro,the main protease of SARS-CoV-2

3C-like protease (3CLpro) processes and liberates functional viral proteins essential for the maturation and infectivity of severe acute respiratory syndrome coronavirus 2, the virus responsible for COVID-19. It has been suggested that 3CLpro is catalytically active as a dimer, making the dimerization interface a target for antiviral development. Guided by structural analysis, here we introduced single amino acid substitutions at nine residues at three key sites of the dimer interface to assess their impact on dimerization and activity. We show that at site 1, alanine substitution of S1 or E166 increased by twofold or reduced relative activity, respectively. At site 2, alanine substitution of S10 or E14 eliminated activity, whereas K12A exhibited ∼60% relative activity. At site 3, alanine substitution of R4, E290, or Q299 eliminated activity, whereas S139A exhibited 46% relative activity. We further found that the oligomerization states of the dimer interface mutants varied; the inactive mutants R4A, R4Q, S10A/C, E14A/D/Q/S, E290A, and Q299A/E were present as dimers, demonstrating that dimerization is not an indication of catalytically active 3CLpro. In addition, present mostly as monomers, K12A displayed residual activity, which could be attributed to the conspicuous amount of dimer present. Finally, differential scanning calorimetry did not reveal a direct relationship between the thermodynamic stability of mutants with oligomerization or catalytic activity. These results provide insights on two allosteric sites, R4/E290 and S10/E14, that may promote the design of antiviral compounds that target the dimer interface rather than the active site of severe acute respiratory syndrome coronavirus 2 3CLpro.     

Salmonella enterica serovar Typhimurium chitinases modulate the intestinal glycome and promote small intestinal invasion

Salmonella enterica serovar Typhimurium (S. Typhimurium) is one of the leading causes of food-borne illnesses worldwide. To colonize the gastrointestinal tract, S. Typhimurium produces multiple virulence factors that facilitate cellular invasion. Chitinases have been recently emerging as virulence factors for various pathogenic bacterial species, and the S. Typhimurium genome contains two annotated chitinases: STM0018 (chiA) and STM0233. However, the role of these chitinases during S. Typhimurium pathogenesis is unknown. The putative chitinase STM0233 has not been studied previously, and only limited data exists on ChiA. Chitinases typically hydrolyze chitin polymers, which are absent in vertebrates. However, chiA expression was detected in infection models and purified ChiA cleaved carbohydrate subunits present on mammalian surface glycoproteins, indicating a role during pathogenesis. Here, we demonstrate that expression of chiA and STM0233 is upregulated in the mouse gut and that both chitinases facilitate epithelial cell adhesion and invasion. S. Typhimurium lacking both chitinases showed a 70% reduction in invasion of small intestinal epithelial cells in vitro. In a gastroenteritis mouse model, chitinase-deficient S. Typhimurium strains were also significantly attenuated in the invasion of small intestinal tissue. This reduced invasion resulted in significantly delayed S. Typhimurium dissemination to the spleen and the liver, but chitinases were not required for systemic survival. The invasion defect of the chitinase-deficient strain was rescued by the presence of wild-type S. Typhimurium, suggesting that chitinases are secreted. By analyzing N-linked glycans of small intestinal cells, we identified specific N-acetylglucosamine-containing glycans as potential extracellular targets of S. Typhimurium chitinases. This analysis also revealed a differential abundance of Lewis X/A-containing glycans that is likely a result of host cell modulation due to the detection of S. Typhimurium chitinases. Similar glycomic changes elicited by chitinase deficient strains indicate functional redundancy of the chitinases. Overall, our results demonstrate that S. Typhimurium chitinases contribute to intestinal adhesion and invasion through modulation of the host glycome.     

A Possible Novel Protective Effect of Piceatannol against Isoproterenol (ISO)-Induced Histopathological,Histochemical, and Immunohistochemical Changes in Male Wistar Rats

Dry mouth is characterized by lower saliva production and changes in saliva composition. In patients with some salivary gland function remaining, pharmaceutical treatments are not recommended; therefore, new, more effective methods of promoting saliva production are needed. Hence, this study aimed to provide an overview of the histological changes in the salivary gland in the model of isoproterenol (ISO)-induced degenerative changes in male Wistar rats and to evaluate the protective effect of piceatannol. Thirty-two male Wistar rats were randomly divided into four groups: the control group, the ISO group, and the piceatannol (PIC)-1, and -2 groups. After the third day of the experiment, Iso (0.8 mg/100 g) was injected intraperitoneally (IP) twice daily into the animals. PIC was given IP in different daily doses (20 and 40 mg/kg) for three days before ISO and seven days with ISO injection. The salivary glands were rapidly dissected and processed for histological, histochemical, immunohistochemical (Ki-67), and morphometric analysis. Upon seven days of treatment with ISO, marked hypertrophy was observed, along with an increased number of positive Ki-67 cells. Proliferation was increased in some endothelial cells as well as in ducts themselves. Despite the significant decrease in proliferation activity, the control group did not return to the usual activity level after treatment with low-dose PIC. Treatment with a high dose of PIC reduced proliferative activity to the point where it was substantially identical to the results seen in the control group. An ISO-driven xerostomia model showed a novel protective effect of piceatannol. A new era of regenerative medicine is dawning around PIC’s promising role.     

Selenium nanoparticles enhance the efficacy of homologous vaccine against the highly pathogenic avian influenza H5N1 virus in chickens

A proper vaccination against avian influenza viruses in chicken can significantly reduce the risk of human infection. Egypt has the highest number of recorded humans highly pathogenic avian influenza (HPAI)-H5N1 infections worldwide despite the widespread use of homologous vaccines in poultry. Enhancing H5N1 vaccine efficacy is ultimately required to better control HPAI-H5N1. The aim of this study is to boost chicken immunity by combined with inactivated HPAI-H5N1 with selenium nanoparticles (SeNPs). The chickens groups 1–3 were fed diets supplemented with SeNPs concentrations (0.25, 0.5, and 1 mg/kg) for 3 weeks and then vaccinated (inactivated HPAI-H5N1). while groups 4,5 and 6 were fed with SeNPs free diets and administered with 0.5 ml of the vaccine combined with 0.02, 0.06, and 0.1 mg/dose of SeNPs and then all groups were challenged with homologous virus 3 weeks post-vaccination (WPV). Group 7, 8 were used as control positive and negative respectively. At 4, 5, and 6 WPV, antibody titer was considerably higher in the group fed a meal supplemented with 1 mg SeNPs/kg. In contrast, both methods of SeNPs supplementation significantly increased the Interleukin 2 (IL2), Interleukin 6 (IL6), and Interferon γ (IFNγ) expressions in the blood cells in a dose-dependent manner, with a higher expression observed in the group that was vaccinated with 0.1 mg/dose. After the challenge, all groups that received SeNPs via diet or vaccines dose showed significant reduction in viral shedding and milder inflammation in lung, trachea, spleen, and liver in addition to higher expression of IL2, IL6, and IFNγ, with the highest expression observed in the group that was vaccinated with 0.1 mg/dose compared the plain vaccinated group. The groups of 1 mg SeNPs/kg and combined vaccinated with 0.1 mg/dose showed the best vaccine efficacy. However, the group vaccinated with 0.1 mg/dose showed the earliest reduction in viral shedding. Overall, SeNPs supplementation in the diet and the administration of the vaccine formula with SeNPs could enhance vaccine efficacy and provide better protection against HPAI-H5N1 in chickens by enhancing cellular immunity and reducing inflammation. We recommend using SeNPs as a vaccine combination or feeding with diet to increase the immunity and vaccine efficacy against H5N1.     

Cytochemical study of the ovary cells in the chick embryo

In the present work, cytochemical studies of mucosubstances, 3-beta-hydroxysteroid dehydrogenase and lipids in the different cellular types of chick embryo female gonads were performed, at 7, 11, 15, and 19 days of embryonal development. Oocytes from the cortical zone of the left ovary were characterized by the presence of a juxtanuclear cytoplasmic cap, which was basophilic, PAS positive, alcianophilic and acidophilic and was related to Balbiani's vitelline body. These staining characteristics either decreased or disappeared from 15 days in oocytes of the normal left ovary medulla as well as in oocytes of the atrophic right ovary.     

Antileukemic activity of sulfoxide nutraceutical allicin against THP-1 cells is associated with premature phosphatidylserine exposure in human erythrocytes

BackgroundAllicin (ACN), a sulfoxide in freshly crushed garlic, is known for its diverse bioactive properties. Among the most notable effects of ACN is its antitumor activity against a wide array of cancer types. Thus, ACN may be a promising anticancer therapeutic. Nevertheless, chemotherapy-induced anemia is a major obstacle in cancer management with a prevalence of up to 70%. Although the pathophysiology behind it remains elusive, a number of medications known to cause anemia in patients have been shown to induce premature programmed cell death in red blood cells (RBCs) known as eryptosis. This study, thus, investigates the anticancer potential of ACN against THP-1 monocytic leukemia cells, its toxic effects on human RBCs, and delineate the underlying biochemical mechanisms.MethodsCytotoxicity was detected using the MTT assay, while hemoglobin leakage was used as a surrogate for hemolysis which was photometrically measured. Major eryptotic events were examined using flow cytometry with fluorescent probes. Phosphatidylserine (PS) exposure was detected by Annexin-V-FITC, cytosolic calcium with Fluo4/AM, and reactive oxygen species with H₂DCFDA.ResultsOur results show that ACN induces hemolysis in a dose-dependent fashion, which is significantly abrogated in absence of extracellular calcium. Moreover, ACN stimulates PS exposure, intracellular calcium overload, and oxidative stress. Using small-molecule inhibitors, we demonstrate that the pro-eryptotic activity of ACN is ameliorated in presence of zVAD(OMe)-FMK, SB203580, and D4476.ConclusionACN possesses both hemolytic and eryptotic properties mediated through elevated intracellular calcium levels, oxidative stress, caspase, p38 MAPK, and CK1α.