Background: Despite considerable advancements in identifying factors contributing to the development of hepatocellular carcinoma(HCC), the pathogenesis of HCC remains unclear. In many cases, HCC is a consequence of pr...Background: Despite considerable advancements in identifying factors contributing to the development of hepatocellular carcinoma(HCC), the pathogenesis of HCC remains unclear. In many cases, HCC is a consequence of prolonged liver fibrosis, resulting in the formation of an intricate premalignant microenvironment. The accumulation of extracellular matrix(ECM) is a hallmark of premalignant microenvironment. Given the critical role of different matrix components in regulating cell phenotype and function, this study aimed to elucidate the interplay between the fibrotic matrix and malignant features in HCC. Methods: Liver tissues from both control(normal) and carbon tetrachloride(CCl_(4))-induced fibrotic rats were decellularized using sodium dodecyl sulfate(SDS) and Triton X-100. The resulting hydrogel from decellularized ECM was processed into micro-particles via the water-in-oil emulsion method. Microparticles were subsequently incorporated into three-dimensional liver biomimetic micro-tissues(MTs) comprising Huh-7 cells, human umbilical vein endothelial cells(HUVECs), and LX-2 cells. The MTs were evaluated using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium(MTS) assay at day 11, immunofluorescence staining, immunoblotting, and spheroid migration assay at day 14 after co-culture. Results: Fibrotic matrix from CCl4-treated rat livers significantly enhanced the growth rate of the MTs and their expression of CCND1 as compared to the normal one. Fibrotic matrix, also induced the expression of epithelial-to-mesenchymal transition(EMT)-associated genes such as TWIST1, ACTA2, MMP9, CDH2, and VIMENTIN in the MTs as compared to the normal matrix. Conversely, the expression of CDH1 and hepatic maturation genes HNF4A, ALB, CYP3A4 was decreased in the MTs when the fibrotic matrix was used. Furthermore, the fibrotic matrix increased the migration of the MTs and their secretion of alpha-fetoprotein. Conclusions: Our findings suggest a regulatory role for the fibrotic matrix in promoting cancerous phenotype, which could potentially accelerate the progression of malignancy in the liver.展开更多
Electrospun nanofibers combined with a wide range of functional additives can be used for a various tissue engineering applications due to their desired biomimetic and physicochemical properties.Therefore,the present ...Electrospun nanofibers combined with a wide range of functional additives can be used for a various tissue engineering applications due to their desired biomimetic and physicochemical properties.Therefore,the present study was conducted to obtain a highly efficient nanocomposite electrospun scaffold with appropriate physicochemical performance and biological properties based on Polycaprolactone/Polyurethane(PCL/PU)mixed with gold nanoparticles(GNPs)and soybean oil(SO).In the present study,the desired nanofibers were fabricated by electrospinning PCL/PU mixed solution with GNPs and SO.The nanocomposite electrospun PU/PCL/SO/GNP nanofibers were characterized in terms of chemical composition by attenuated total reflectance-Fourier transform infrared spectroscopy(ATR-FTIR),morphological structure by field-emission scanning electron microscopy(FE-SEM),and mechanical and biological properties.The surface topography and wettability were determined by atomic force microscopy(AFM)and water contact angle measurements,respectively.It was found that the presence of GNPs along with SO in the structure of PCL/PU nanofiber created a smoother surface in terms of surface roughness and also a more homogeneous fibrous structure.In addition,it was observed that both SO and GNPs caused an increase in the electrical conductivity of the fibrous mats.In the biocompatibility evaluations by measuring cell viability and cell adherence to the scaffold's surfaces,it was found that adding of SO and GNPs supports fibroblasts.Taken together,the fabricated nanocomposite fibrous scaffolds can be a potential candidate for various tissue engineering purposes.展开更多
Multicellular microtissues of primary human hepatocytes(PHHs)co-cultured with other supporting cell types are a promis-ing model for drug screening and toxicological studies.However,these liver microtissues(LMs)rapidl...Multicellular microtissues of primary human hepatocytes(PHHs)co-cultured with other supporting cell types are a promis-ing model for drug screening and toxicological studies.However,these liver microtissues(LMs)rapidly lose their functions during ex vivo culture.Here,in order to mimic the cellular and structural hepatic microenvironment,we co-cultured PHHs with human mesenchymal stromal cells(MSCs)and human umbilical vein endothelial cells(HUVECs)in the presence of cell-sized microparticles(MPs)derived from liver extracellular matrix(LEMPs).The microwell culture platform enabled biofabrication of size-controlled multicellular microtissues(PHH:HUVEC:MSC=3:2:1)with efficient LEMP incorporation(about 70%at a 2:1 ratio of cells:MP).The biofabricated liver microtissues(BLMs)were cultured ex vivo for 14 days and compared to the cell-only LM in terms of gene and protein expression,functional activity,cytochrome P450(CYP450)enzyme inducibility,and drug sensitivity.The results supported superior hepatic-related gene expression,functional activity,and polarity for PHH in BLM compared to LM.CYP450 enzyme inducibility and dose-responsive sensitivity to toxic drugs were significantly higher in the BLM group.In conclusion,microtissue engineering by incorporation of tissue-specific microparticles within a multicellular microtissue can offer some advantages for drug discovery studies and cell transplantation applications.In the near future,this approach could generate a scalable platform of several functional biofabricated microtissues representing different organs.展开更多
Objective:Menstrual blood-derived stem cells from endometriosis patients(E-MenSCs)have different gene expression patterns than those from healthy nonendometriotic females(NE-MenSCs).Exosomes extracted from mesenchymal...Objective:Menstrual blood-derived stem cells from endometriosis patients(E-MenSCs)have different gene expression patterns than those from healthy nonendometriotic females(NE-MenSCs).Exosomes extracted from mesenchymal stem cells and plants are considered for the treatment of various diseases.This study aimed to compare the effects of exosomes derived from NE-MenSCs(C-exos)and those from the roots of ginger(P-exos)on E-MenSCs.Methods:E-MenSCs at the third passage were used,and after evaluating the effective dosage with MTT,C-exos(200µg/mL)or P-exos(100µg/mL)were added to treat them.Following a 72-h incubation,the cells were analyzed with annexin V/PI test to evaluate the apoptosis rate.Also,genes related to inflammation(IL-6,IL-8,IL-1β,NF-κB,COX2),cell cycle(Cyclin D1),the steroid pathway(ESR1),migration and invasion(MMP-2,MMP-9,VEGF),and the apoptosis pathway(BAX,BCL2)were detected by real-time PCR.Results:Apoptosis was increased in both the P-and C-exos groups.The expression levels of IL-6 and IL-1βwere significantly lower in the P-exos group than in the E-MenSCs group.The expression levels of IL-8,NF-κB,COX-2,and MMP-9 were significantly decreased in both the P-exos group and the C-exos group.The expression level of VEGF was significantly lower in the P-exos group than in the E-MenSCs group.The BAX/BCL2 ratio was much lower in the P-exos group than in the E-MenSCs group.Conclusion:In this study,we established the feasibility of using a novel natural nontoxic material to target endometriotic mesenchymal stem cells to modify their gene expression and function toward healthy cells.Both C-exos and P-exos showed positive effects on the gene expression and function of endometriotic cells.Considering that plant exosomes are easier to access and less expensive,they can be considered for clinical use in improving the symptoms of endometriosis patients.展开更多
Our previous studies have histomorphologically confirmed that nanofibrous poly（3-hydroxybutyrate- co-3-hydroxyvalerate） conduit can be used to repair 30-mm-long sciatic nerve defects. However, the repair effects on ...Our previous studies have histomorphologically confirmed that nanofibrous poly（3-hydroxybutyrate- co-3-hydroxyvalerate） conduit can be used to repair 30-mm-long sciatic nerve defects. However, the repair effects on rat behaviors remain poorly understood. In this study, we used nanofibrous poly（3-hydroxybutyrate-co-3-hydroxyvalerate） conduit and autologous sciatic nerve to bridge 30-ram-long rat sciatic nerve gaps. Within 4 months after surgery, rat sciatic nerve functional re- covery was evaluated per month by behavioral analyses, including toe out angle, toe spread anal- ysis, walking track analysis, extensor postural thrust, swimming test, open-field analysis and no- ciceptive function. Results showed that rat sciatic nerve functional recovery was similar after nanofibrous poly（3-hydroxybutyrate-co-3-hydroxyvalerate） conduit and autologous nerve grafting. These findings suggest that nanofibrous poly（3-hydroxybutyrate-co-3-hydroxyvalerate） conduit is suitable in use for repair of long-segment sciatic nerve defects.展开更多
Several studies have demonstrated that selective serotonin reuptake inhibitor antidepressants can promote neuronal cell proliferation and enhance neuroplasticity both in vitro and in vivo. It is hypothesized that cita...Several studies have demonstrated that selective serotonin reuptake inhibitor antidepressants can promote neuronal cell proliferation and enhance neuroplasticity both in vitro and in vivo. It is hypothesized that citalopram, a selective serotonin reuptake inhibitor, can promote the neuronal differentiation of adult bone marrow mesenchymal stem cells. Citalopram strongly enhanced neuronal characteristics of the cells derived from bone marrow mesenchymal stem cells. The rate of cell death was decreased in citalopram-treated bone marrow mesenchymal stem cells than in control cells in neurobasal medium. In addition, the cumulative population doubling level of the citalopram-treated cells was signiifcantly increased compared to that of control cells. Also BrdU incorporation was elevated in citalopram-treated cells. These ifndings suggest that citalopram can improve the neuronal-like cell differentiation of bone marrow mesenchymal stem cells by increasing cell proliferation and survival while maintaining their neuronal characteristics.展开更多
Functionalized hydrogels stimulate the migration and morphogenesis of endothelial cells(ECs)and are useful substrates for wound healing.The present study investigates the feasibility of covalent conjugation of taurine...Functionalized hydrogels stimulate the migration and morphogenesis of endothelial cells(ECs)and are useful substrates for wound healing.The present study investigates the feasibility of covalent conjugation of taurine(Tau)on a gelatin-based hydrogel.This hydrogel is expected to maintain positive charged growth factors such as basic fibroblast growth factor(bFGF)and vascular endothelial growth factors(VEGFs)near ECs within the hydrogel microenvironment.The gelatin was conjugated with hydroxyl phenol(Ph)and Tau moieties,and in following that Ph residues were crosslinked through a horseradish peroxidase-catalyzed reaction.The migration characteristics of ECs were analyzed by scratch migration assay and microparticle-based cell migration assay.Cellular morphology and amounts of angiopoietin 1(Ang 1),bFGF,and VEGF proteins were evaluated for encapsulated cells.The potential of synthesized hydrogels in wound healing was assessed by the percentage of reduction from the original wound size and histopathological analyses of rat skin.The incorporated Tau molecules within the hydrogel remained stable through covalent bonds during incubation.During extended incubation,the gelatin-based hydrogel conjugated with Tau improved the migration distance and number of existing migrated ECs.Immobilized Tau within the gelatin-based hydrogel induced high motility of ECs,accompanied by robust cytoskeleton extension and a cell subpopulation that expressed CD44 and CD31 receptors as well as enhancement of Ang 1,bFGF,and VEGF.We found that injectable Gel-Ph-Tau effectively improves wound-healing parameters.展开更多
The utilization of biomarkers for in vivo and in vitro research is growing rapidly. This is mainly due to the enormous potential of biomarkers in evaluating molecular and cellular abnormalities in cell models and in t...The utilization of biomarkers for in vivo and in vitro research is growing rapidly. This is mainly due to the enormous potential of biomarkers in evaluating molecular and cellular abnormalities in cell models and in tissue, and evaluating drug responses and the effectiveness of therapeutic intervention strategies. An important way to analyze the development of the human body is to assess molecular markers in embryonic specialized cells, which include the ectoderm, mesoderm, and endoderm. Neuronal development is controlled through the gene networks in the neural crest and neural tube, both components of the ectoderm. The neural crest differentiates into several different tissues including, but not limited to, the peripheral nervous system, enteric nervous system, melanocyte, and the dental pulp. The neural tube eventually converts to the central nervous system. This review provides an overview of the differentiation of the ectoderm to a fully functioning nervous system, focusing on molecular biomarkers that emerge at each stage of the cellular specialization from multipotent stem cells to completely differentiated cells. Particularly, the otic placode is the origin of most of the inner ear cell types such as neurons, sensory hair cells, and supporting cells. During the development, different auditory cell types can be distinguished by the expression of the neurogenin differentiation factor1 (Neuro D1), Brn3a, and transcription factor GATA3. However, the mature auditory neurons express other markers including bIII tubulin, the vesicular glutamate transporter (VGLUT1), the tyrosine receptor kinase B and C (Trk B, C), BDNF, neurotrophin 3 (NT3), Calretinin, etc.展开更多
It has been confirmed that nanofibrous poly（3-hydroxybutyrate-co-3-hydroxyvalerate） nerve conduit can promote peripheral nerve regeneration in rats. However, its efficiency in repair of over 30-mm-long sciatic nerve...It has been confirmed that nanofibrous poly（3-hydroxybutyrate-co-3-hydroxyvalerate） nerve conduit can promote peripheral nerve regeneration in rats. However, its efficiency in repair of over 30-mm-long sciatic nerve defects needs to be assessed. In this study, we used a nanofibrous poly（3-hydroxybutyrate-co-3-hydroxyvalerate） nerve conduit to bridge a 30-mm-long gap in the rat sciatic nerve. At 4 months after nerve conduit implantation, regenerated nerves were macroscopi- cally observed and histologically assessed. In the nanofibrous graft, the rat sciatic nerve trunk had been reconstructed by restoration of nerve continuity and formation of myelinated nerve fiber. There were Schwann cells and glial cells in the regenerated nerves. Masson＇s trichrome staining showed that there were no pathological changes in the size and structure of gastrocnemius muscle cells on the operated side of rats. These findings suggest that nanofibrous poly（3-hydroxybutyrate-co-3- hydroxyvalerate） nerve conduit is suitable for repair of long-segment sciatic nerve defects.展开更多
Objective: To evaluate the impact of Olea (O.) europaea extract on markers of oxidative stress and apoptosis of ovarian tissues in a rat model of torsion/detorsion-induced ovarian damage. Methods: A total of 28 Wistar...Objective: To evaluate the impact of Olea (O.) europaea extract on markers of oxidative stress and apoptosis of ovarian tissues in a rat model of torsion/detorsion-induced ovarian damage. Methods: A total of 28 Wistar female rats were randomly assigned into 4 groups, with 7 rats in each group. The sham group received a 2.5 cm longitudinal incision in the midline part of the abdomen which was then sutured with 5-0 nylon thread;the torsion/detorsion group underwent torsion induction for 3 h followed by reperfusion for 10 days;the torsion/detorsion+O. europaea group received 300 mg/kg hydro-alcoholic extract of O. europaea 30 min before detorsion, followed by reperfusion for 10 days;and the O. europaea group only received 300 mg/kg hydro-alcoholic extract of O. europaea for 10 days. After the treatment period, blood samples were taken;the levels of estrogen, glutathione peroxidase, superoxide dismutase, and malondialdehyde were assayed. The histological changes, as well as the rate of apoptosis in ovarian tissues, were also carried out by histomorphometric analysis at day 10 post-procedure. Results: Histological comparisons demonstrated a significant detrimental change in the torsion/detorsion group as compared with other groups. The number of pre-antral and antral follicles and corpus luteum was significantly decreased in the torsion/detorsion group compared with the sham group, while treatment with O. europaea could enhance their numbers (P<0.05). The index of apoptosis and the number of atretic body in the ovarian tissue were significantly higher in the torsion/detorsion group compared with the sham group (P<0.05). The concentrations of glutathione peroxidase, estrogen, and superoxide dismutase as well as the mRNA expression of Bcl-2 were considerably diminished in the torsion/detorsion group while they were elevated in the torsion/detorsion+O. europaea group (P<0.05) compared with the torsion/detorsion group. The serum malondialdehyde level and the mRNA expression of Bax were markedly increased during ischemia, while treatment with O. europaea significantly diminished the increased concentrations of malondialdehyde and Bax level in the torsion/detorsion+O. europaea group (P<0.05). Conclusions: O. europaea extract can reduce the degree of tissue damage induced by oxidative stress and apoptosis in the ovary following ovarian ischemia/reperfusion.展开更多
The functional properties of endogenous Schwann cells(SCs)during nerve repair are dynamic.Optimizing the functional properties of SCs at different stages of nerve repair may have therapeutic benefit in improving the r...The functional properties of endogenous Schwann cells(SCs)during nerve repair are dynamic.Optimizing the functional properties of SCs at different stages of nerve repair may have therapeutic benefit in improving the repair of damaged nerves.Previous studies showed that miR-221-3p promotes the proliferation and migration of SCs,and miR-338-3p promotes the myelination of SCs.In this study,we established rat models of sciatic nerve injury by bridging the transected sciatic nerve with a silicone tube.We injected a miR-221 lentiviral vector system together with a doxycycline-inducible Tet-On miR-338 lentiviral vector system into the cavity of nerve conduits of nerve stumps to sequentially regulate the biological function of endogenous SCs at different stages of nerve regeneration.We found that the biological function of SCs was sequentially regulated,the diameter and density of myelinated axons were increased,the expression levels of NF200 and myelin basic protein were increased,and the function of injured peripheral nerve was improved using this system.miRNA Target Prediction Database prediction,Nanopore whole transcriptome sequencing,quantitative PCR,and dual luciferase reporter gene assay results predicted and verified Cdkn1b and Nrp1 as target genes of miR-221-3p and miR-338-3p,respectively,and their regulatory effects on SCs were confirmed in vitro.In conclusion,here we established a new method to enhance nerve regeneration through sequential regulation of biological functions of endogenous SCs,which establishes a new concept and model for the treatment of peripheral nerve injury.The findings from this study will provide direct guiding significance for clinical treatment of sciatic nerve injury.展开更多
The ultimate goal of tissue engineering is to design and fabricate functional human tissues that are similar to natural cells and are capable of regeneration.Preparation of cell aggregates is one of the important step...The ultimate goal of tissue engineering is to design and fabricate functional human tissues that are similar to natural cells and are capable of regeneration.Preparation of cell aggregates is one of the important steps in 3D tissue engineering technology,particularly in organ printing.Two simple methods,hanging drop(HD)and conical tube(CT)were utilized to prepare cell aggregates.The size and viability of the aggregates obtained at different initial cell densities and pre-culture duration were compared.The proliferative ability of the cell aggregates and their ability to spread in culture plates were also investigated.In both methods,the optimum average size of the aggregates was less than 500μm.CT aggregates were smaller than HD aggregates.5,000 cells per drop HD aggregates showed a marked ability to attach and spread on the culture surface.The proliferative ability reduced when the initial cell density was increased.Comparing these methods,we found that the HD method having better size controlling ability as well as enhanced ability to maintain higher rates of viability,spreading,and proliferation.In conclusion,smaller HD aggregates might be a suitable choice as building blocks for making bioink particles in bioprinting technique.展开更多
Given the anatomic complexity at the bifurcation point of a nerve trunk,enforced suturing between stumps can lead to misdirection of nerve axons,thereby resulting in adverse consequences.We assumed that Y-tube conduit...Given the anatomic complexity at the bifurcation point of a nerve trunk,enforced suturing between stumps can lead to misdirection of nerve axons,thereby resulting in adverse consequences.We assumed that Y-tube conduits injected with human umbilical cord stem cells could be an effective method to solve such problems,but studies focused on the best type of Y-tube conduit remain controversial.Therefore,the present study evaluated the applicability and efficacy of various types of Y-tube conduits containing human umbilical cord stem cells for treating rat femoral nerve defects on their bifurcation points.At 12 weeks after the bridging surgery that included treatment with different types of Y-tube conduits,there were no differences in quadriceps femoris muscle weight or femoral nerve ultrastructure.However,the Y-tube conduit group with longer branches and a short trunk resulted in a better outcome according to retrograde labeling and electrophysiological analysis.It can be concluded from the study that repairing a mixed nerve defect at its bifurcation point with Y-tube conduits,in particular those with long branches and a short trunk,is effective and results in good outcomes.展开更多
Lead exposure induces decreased hippocampal N-methyI-D-aspartic acid （NMDA） receptor gene and protein expressions, which influences the molecular mechanisms of learning and memory. However, lead poisoning-induced di...Lead exposure induces decreased hippocampal N-methyI-D-aspartic acid （NMDA） receptor gene and protein expressions, which influences the molecular mechanisms of learning and memory. However, lead poisoning-induced differences in NMDA subunit expression, and the correlation of lead poisoning with learning and memory, remain poorly understood. The present study measured differences in expression of NMDA receptor subunits NR1, NR2A, and NR2B in memory-related brain regions of rats who underwent different doses of lead exposure. Results demonstrated decreased NR1, NR2A, and NR2B subunit expressions in some memory-related brain areas. The inhibitory effect of 4.8 mmol/L lead exposure on hippocampal NR2B was most significant, although NR2A expression also significantly decreased following 14.4 mmol/L lead exposure. There was no difference in NR1 expression following exposure to 〈 4.8 mmol/L lead, although the inhibitory effect of 19.6 mmol/L lead exposure was strongest for NR1 expression in the hippocampus. Inhibitory avoidance test results revealed that greater concentrations of lead exposure resulted in decreased learning and memory. Therefore, lead toxicity was dependent on NMDA receptor subunit composition, and NR1, NR2A, and NR2B expressions were associated with time and concentration of lead exposure.展开更多
This article presents the construction of scaffolds composed of polylactic acid(PLA)with different concentrations of hydroxyapatite(HA)by electrospinning,which were superficially modified with polypyrrole(PPy/I)by pla...This article presents the construction of scaffolds composed of polylactic acid(PLA)with different concentrations of hydroxyapatite(HA)by electrospinning,which were superficially modified with polypyrrole(PPy/I)by plasma polymerization.A preliminary study was conducted of the biological and mechanical behavior of the scaffolds when they were implanted in the back of rabbits for 30 days;bone cells differentiated from mesenchymal stem cells(MSCs)were used.The bone cell and scaffold structures were characterized by histological,immunohistochemical,and mechanical stress tests.Hematoxylin–eosin staining showed good tissue conformation.The immunohistochemical tests highlighted the presence of the main bone tissue proteins,such as collagen,osteocalcin,and osteopontin.The PLA/HA scaffolds were observed to exhibit cell adhesion and proliferation properties;however,the response was much better in the scaffolds that had a higher concentration of HA and that were coated with PPy/I.The results of the mechanical tests of the scaffolds indicated that the plasma treatment improved the adhesion and cell proliferation properties and contributed to the mechanical support,allowing the formation of neotissues with good viability of cell growth.展开更多
The Klotho.(KL)gene is related to aging.In this study,SKL(secreted KL)and heparin were cross:linked to the acellular small intestinal submucosa(SIS).Based on this,small-diameter tissue engineered blood vessels(TEVs)we...The Klotho.(KL)gene is related to aging.In this study,SKL(secreted KL)and heparin were cross:linked to the acellular small intestinal submucosa(SIS).Based on this,small-diameter tissue engineered blood vessels(TEVs)were constructed.The role of SKL on improving the patency of TEVs through promoting cell adherence was investigated.The SIS membrane was cross linked with heparin and SKL,respectively,to prepare heparin group and SKL group artificial blood vessels.The CCK8 assay showed that SKL treatment promoted endothelial cells proliferation.Western blot showed that SKL upregulated the levels of FAK and RHOA.展开更多
The presence of endometrial tissue outside of the uterine cavity is named endometriosis and is the most common gynecologic disorder in women. Determining the inhibitory effect of a Deforolimus on angiogenesis in a thr...The presence of endometrial tissue outside of the uterine cavity is named endometriosis and is the most common gynecologic disorder in women. Determining the inhibitory effect of a Deforolimus on angiogenesis in a three-dimensional (3-D) culture of human endometrial stromal cells (hEnCs) in vitro. The important mechanism in the pathogenesis of endometriosis is angiogenesis, and deforolimus has been shown to have anti-angiogenic activity. This was an in vitro study of human endometrial stromal cells in 3-D culture of fibrin matrix. Endometrial stromal cells isolated and placed in a 3-D fibrin matrix culture system for angiogenesis with VEGF and inhibit angiogenesis by deforolimus. Finally these cells analyzed by CD31 antibodies. After 3 weeks, in cells treated with VEGF, endothelial cell branching was observed and rudimentary capillary-like structures formed. In the presence of 5μM of deforolimus, angiogenesis was reduced. The deforolimus were shown to be effective in inhibiting the mechanisms of angiogenesis.展开更多
SARS-CoV-2 is a novel RNA coronavirus responsible of a deadly pandemic: the clinical illness COVID-19. With only one authorized drug for emergency use in critically ill patients: Remdesivir, there is not any other app...SARS-CoV-2 is a novel RNA coronavirus responsible of a deadly pandemic: the clinical illness COVID-19. With only one authorized drug for emergency use in critically ill patients: Remdesivir, there is not any other approved drug or vaccine yet with proven potential to overcome this infection. We exposed here many scientific evidences to support our novel idea that a macrolide, basically Clarithromycin, could be effective as a single agent for treatment and prophylaxis of COVID-19. Clarithromycin could change the history of this pandemic. It could reduce the costs of treatment and the potential adverse effects when combining more than one drug such as with Hydroxychloroquine. Clarithromycin treatment and prophylaxis as a single agent could be much more simple, safe and cheaper as giving Chloroquine or Hydroxychloroquine alone or in combination with Azithromycin as well as other therapeutic options.展开更多
Human stromal stem cells derived from endometrium (hESCs) are a type of multipotent stromal cells of the proven ability to differentiate into osteogenic lineage. Thus, it was suggested that these cells may be used to ...Human stromal stem cells derived from endometrium (hESCs) are a type of multipotent stromal cells of the proven ability to differentiate into osteogenic lineage. Thus, it was suggested that these cells may be used to repair skeletal defects. In this study, Human ESCs were extracted from female endometrium and harvested. Biomimetic gelatin/apatite (Gel/Ap) scaffolds with and without harvested cells were implanted in a Critical size calvarial defects in the cranial bone of adult male rat. To CT-Scan and Histological studies were performed to investigate the level of bone formation after 8 weeks of surgery. Results confirmed that the treated defects with the bare and hESCs grafted Gel/Ap scaffold showed significant bone formation and maturation in comparison with the control group.展开更多
基金financially supported by grants from Royan In-stitute(grant No.400000200)Bahar Tashkhis Teb Co.(BTT,9703,9809,and 9903)。
文摘Background: Despite considerable advancements in identifying factors contributing to the development of hepatocellular carcinoma(HCC), the pathogenesis of HCC remains unclear. In many cases, HCC is a consequence of prolonged liver fibrosis, resulting in the formation of an intricate premalignant microenvironment. The accumulation of extracellular matrix(ECM) is a hallmark of premalignant microenvironment. Given the critical role of different matrix components in regulating cell phenotype and function, this study aimed to elucidate the interplay between the fibrotic matrix and malignant features in HCC. Methods: Liver tissues from both control(normal) and carbon tetrachloride(CCl_(4))-induced fibrotic rats were decellularized using sodium dodecyl sulfate(SDS) and Triton X-100. The resulting hydrogel from decellularized ECM was processed into micro-particles via the water-in-oil emulsion method. Microparticles were subsequently incorporated into three-dimensional liver biomimetic micro-tissues(MTs) comprising Huh-7 cells, human umbilical vein endothelial cells(HUVECs), and LX-2 cells. The MTs were evaluated using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium(MTS) assay at day 11, immunofluorescence staining, immunoblotting, and spheroid migration assay at day 14 after co-culture. Results: Fibrotic matrix from CCl4-treated rat livers significantly enhanced the growth rate of the MTs and their expression of CCND1 as compared to the normal one. Fibrotic matrix, also induced the expression of epithelial-to-mesenchymal transition(EMT)-associated genes such as TWIST1, ACTA2, MMP9, CDH2, and VIMENTIN in the MTs as compared to the normal matrix. Conversely, the expression of CDH1 and hepatic maturation genes HNF4A, ALB, CYP3A4 was decreased in the MTs when the fibrotic matrix was used. Furthermore, the fibrotic matrix increased the migration of the MTs and their secretion of alpha-fetoprotein. Conclusions: Our findings suggest a regulatory role for the fibrotic matrix in promoting cancerous phenotype, which could potentially accelerate the progression of malignancy in the liver.
基金funded by Department of Medical Nanotechnology,Faculty of Advanced Medical Sciences,Tabriz University of Medical Sciences (Grant NO:62379).
文摘Electrospun nanofibers combined with a wide range of functional additives can be used for a various tissue engineering applications due to their desired biomimetic and physicochemical properties.Therefore,the present study was conducted to obtain a highly efficient nanocomposite electrospun scaffold with appropriate physicochemical performance and biological properties based on Polycaprolactone/Polyurethane(PCL/PU)mixed with gold nanoparticles(GNPs)and soybean oil(SO).In the present study,the desired nanofibers were fabricated by electrospinning PCL/PU mixed solution with GNPs and SO.The nanocomposite electrospun PU/PCL/SO/GNP nanofibers were characterized in terms of chemical composition by attenuated total reflectance-Fourier transform infrared spectroscopy(ATR-FTIR),morphological structure by field-emission scanning electron microscopy(FE-SEM),and mechanical and biological properties.The surface topography and wettability were determined by atomic force microscopy(AFM)and water contact angle measurements,respectively.It was found that the presence of GNPs along with SO in the structure of PCL/PU nanofiber created a smoother surface in terms of surface roughness and also a more homogeneous fibrous structure.In addition,it was observed that both SO and GNPs caused an increase in the electrical conductivity of the fibrous mats.In the biocompatibility evaluations by measuring cell viability and cell adherence to the scaffold's surfaces,it was found that adding of SO and GNPs supports fibroblasts.Taken together,the fabricated nanocomposite fibrous scaffolds can be a potential candidate for various tissue engineering purposes.
基金supported by Grants from Royan Institute(No.96000165)to MV and HBBahar Tashkhis Teb Co.(Nos.BTT,9702,and 9802)+1 种基金Iran National Science Foundation(No.97014445)to MVthe Ministry of Health and Medical Education(No.56700/147)to HB.
文摘Multicellular microtissues of primary human hepatocytes(PHHs)co-cultured with other supporting cell types are a promis-ing model for drug screening and toxicological studies.However,these liver microtissues(LMs)rapidly lose their functions during ex vivo culture.Here,in order to mimic the cellular and structural hepatic microenvironment,we co-cultured PHHs with human mesenchymal stromal cells(MSCs)and human umbilical vein endothelial cells(HUVECs)in the presence of cell-sized microparticles(MPs)derived from liver extracellular matrix(LEMPs).The microwell culture platform enabled biofabrication of size-controlled multicellular microtissues(PHH:HUVEC:MSC=3:2:1)with efficient LEMP incorporation(about 70%at a 2:1 ratio of cells:MP).The biofabricated liver microtissues(BLMs)were cultured ex vivo for 14 days and compared to the cell-only LM in terms of gene and protein expression,functional activity,cytochrome P450(CYP450)enzyme inducibility,and drug sensitivity.The results supported superior hepatic-related gene expression,functional activity,and polarity for PHH in BLM compared to LM.CYP450 enzyme inducibility and dose-responsive sensitivity to toxic drugs were significantly higher in the BLM group.In conclusion,microtissue engineering by incorporation of tissue-specific microparticles within a multicellular microtissue can offer some advantages for drug discovery studies and cell transplantation applications.In the near future,this approach could generate a scalable platform of several functional biofabricated microtissues representing different organs.
文摘Objective:Menstrual blood-derived stem cells from endometriosis patients(E-MenSCs)have different gene expression patterns than those from healthy nonendometriotic females(NE-MenSCs).Exosomes extracted from mesenchymal stem cells and plants are considered for the treatment of various diseases.This study aimed to compare the effects of exosomes derived from NE-MenSCs(C-exos)and those from the roots of ginger(P-exos)on E-MenSCs.Methods:E-MenSCs at the third passage were used,and after evaluating the effective dosage with MTT,C-exos(200µg/mL)or P-exos(100µg/mL)were added to treat them.Following a 72-h incubation,the cells were analyzed with annexin V/PI test to evaluate the apoptosis rate.Also,genes related to inflammation(IL-6,IL-8,IL-1β,NF-κB,COX2),cell cycle(Cyclin D1),the steroid pathway(ESR1),migration and invasion(MMP-2,MMP-9,VEGF),and the apoptosis pathway(BAX,BCL2)were detected by real-time PCR.Results:Apoptosis was increased in both the P-and C-exos groups.The expression levels of IL-6 and IL-1βwere significantly lower in the P-exos group than in the E-MenSCs group.The expression levels of IL-8,NF-κB,COX-2,and MMP-9 were significantly decreased in both the P-exos group and the C-exos group.The expression level of VEGF was significantly lower in the P-exos group than in the E-MenSCs group.The BAX/BCL2 ratio was much lower in the P-exos group than in the E-MenSCs group.Conclusion:In this study,we established the feasibility of using a novel natural nontoxic material to target endometriotic mesenchymal stem cells to modify their gene expression and function toward healthy cells.Both C-exos and P-exos showed positive effects on the gene expression and function of endometriotic cells.Considering that plant exosomes are easier to access and less expensive,they can be considered for clinical use in improving the symptoms of endometriosis patients.
基金supported by Tonekabon Branch,Islamic Azad University,Tonekabon,Iran,No.73/442453
文摘Our previous studies have histomorphologically confirmed that nanofibrous poly（3-hydroxybutyrate- co-3-hydroxyvalerate） conduit can be used to repair 30-mm-long sciatic nerve defects. However, the repair effects on rat behaviors remain poorly understood. In this study, we used nanofibrous poly（3-hydroxybutyrate-co-3-hydroxyvalerate） conduit and autologous sciatic nerve to bridge 30-ram-long rat sciatic nerve gaps. Within 4 months after surgery, rat sciatic nerve functional re- covery was evaluated per month by behavioral analyses, including toe out angle, toe spread anal- ysis, walking track analysis, extensor postural thrust, swimming test, open-field analysis and no- ciceptive function. Results showed that rat sciatic nerve functional recovery was similar after nanofibrous poly（3-hydroxybutyrate-co-3-hydroxyvalerate） conduit and autologous nerve grafting. These findings suggest that nanofibrous poly（3-hydroxybutyrate-co-3-hydroxyvalerate） conduit is suitable in use for repair of long-segment sciatic nerve defects.
基金funded by the Research Center for Science and Technology in Medicine(RCSTiM),Tehran University of Medical Sciences,Tehran(TUMS),Tehran,Iran
文摘Several studies have demonstrated that selective serotonin reuptake inhibitor antidepressants can promote neuronal cell proliferation and enhance neuroplasticity both in vitro and in vivo. It is hypothesized that citalopram, a selective serotonin reuptake inhibitor, can promote the neuronal differentiation of adult bone marrow mesenchymal stem cells. Citalopram strongly enhanced neuronal characteristics of the cells derived from bone marrow mesenchymal stem cells. The rate of cell death was decreased in citalopram-treated bone marrow mesenchymal stem cells than in control cells in neurobasal medium. In addition, the cumulative population doubling level of the citalopram-treated cells was signiifcantly increased compared to that of control cells. Also BrdU incorporation was elevated in citalopram-treated cells. These ifndings suggest that citalopram can improve the neuronal-like cell differentiation of bone marrow mesenchymal stem cells by increasing cell proliferation and survival while maintaining their neuronal characteristics.
文摘Functionalized hydrogels stimulate the migration and morphogenesis of endothelial cells(ECs)and are useful substrates for wound healing.The present study investigates the feasibility of covalent conjugation of taurine(Tau)on a gelatin-based hydrogel.This hydrogel is expected to maintain positive charged growth factors such as basic fibroblast growth factor(bFGF)and vascular endothelial growth factors(VEGFs)near ECs within the hydrogel microenvironment.The gelatin was conjugated with hydroxyl phenol(Ph)and Tau moieties,and in following that Ph residues were crosslinked through a horseradish peroxidase-catalyzed reaction.The migration characteristics of ECs were analyzed by scratch migration assay and microparticle-based cell migration assay.Cellular morphology and amounts of angiopoietin 1(Ang 1),bFGF,and VEGF proteins were evaluated for encapsulated cells.The potential of synthesized hydrogels in wound healing was assessed by the percentage of reduction from the original wound size and histopathological analyses of rat skin.The incorporated Tau molecules within the hydrogel remained stable through covalent bonds during incubation.During extended incubation,the gelatin-based hydrogel conjugated with Tau improved the migration distance and number of existing migrated ECs.Immobilized Tau within the gelatin-based hydrogel induced high motility of ECs,accompanied by robust cytoskeleton extension and a cell subpopulation that expressed CD44 and CD31 receptors as well as enhancement of Ang 1,bFGF,and VEGF.We found that injectable Gel-Ph-Tau effectively improves wound-healing parameters.
文摘The utilization of biomarkers for in vivo and in vitro research is growing rapidly. This is mainly due to the enormous potential of biomarkers in evaluating molecular and cellular abnormalities in cell models and in tissue, and evaluating drug responses and the effectiveness of therapeutic intervention strategies. An important way to analyze the development of the human body is to assess molecular markers in embryonic specialized cells, which include the ectoderm, mesoderm, and endoderm. Neuronal development is controlled through the gene networks in the neural crest and neural tube, both components of the ectoderm. The neural crest differentiates into several different tissues including, but not limited to, the peripheral nervous system, enteric nervous system, melanocyte, and the dental pulp. The neural tube eventually converts to the central nervous system. This review provides an overview of the differentiation of the ectoderm to a fully functioning nervous system, focusing on molecular biomarkers that emerge at each stage of the cellular specialization from multipotent stem cells to completely differentiated cells. Particularly, the otic placode is the origin of most of the inner ear cell types such as neurons, sensory hair cells, and supporting cells. During the development, different auditory cell types can be distinguished by the expression of the neurogenin differentiation factor1 (Neuro D1), Brn3a, and transcription factor GATA3. However, the mature auditory neurons express other markers including bIII tubulin, the vesicular glutamate transporter (VGLUT1), the tyrosine receptor kinase B and C (Trk B, C), BDNF, neurotrophin 3 (NT3), Calretinin, etc.
基金supported by Tonekabon Branch, Islamic Azad University, Tonekabon, Iran,No. 73/442453
文摘It has been confirmed that nanofibrous poly（3-hydroxybutyrate-co-3-hydroxyvalerate） nerve conduit can promote peripheral nerve regeneration in rats. However, its efficiency in repair of over 30-mm-long sciatic nerve defects needs to be assessed. In this study, we used a nanofibrous poly（3-hydroxybutyrate-co-3-hydroxyvalerate） nerve conduit to bridge a 30-mm-long gap in the rat sciatic nerve. At 4 months after nerve conduit implantation, regenerated nerves were macroscopi- cally observed and histologically assessed. In the nanofibrous graft, the rat sciatic nerve trunk had been reconstructed by restoration of nerve continuity and formation of myelinated nerve fiber. There were Schwann cells and glial cells in the regenerated nerves. Masson＇s trichrome staining showed that there were no pathological changes in the size and structure of gastrocnemius muscle cells on the operated side of rats. These findings suggest that nanofibrous poly（3-hydroxybutyrate-co-3- hydroxyvalerate） nerve conduit is suitable for repair of long-segment sciatic nerve defects.
文摘Objective: To evaluate the impact of Olea (O.) europaea extract on markers of oxidative stress and apoptosis of ovarian tissues in a rat model of torsion/detorsion-induced ovarian damage. Methods: A total of 28 Wistar female rats were randomly assigned into 4 groups, with 7 rats in each group. The sham group received a 2.5 cm longitudinal incision in the midline part of the abdomen which was then sutured with 5-0 nylon thread;the torsion/detorsion group underwent torsion induction for 3 h followed by reperfusion for 10 days;the torsion/detorsion+O. europaea group received 300 mg/kg hydro-alcoholic extract of O. europaea 30 min before detorsion, followed by reperfusion for 10 days;and the O. europaea group only received 300 mg/kg hydro-alcoholic extract of O. europaea for 10 days. After the treatment period, blood samples were taken;the levels of estrogen, glutathione peroxidase, superoxide dismutase, and malondialdehyde were assayed. The histological changes, as well as the rate of apoptosis in ovarian tissues, were also carried out by histomorphometric analysis at day 10 post-procedure. Results: Histological comparisons demonstrated a significant detrimental change in the torsion/detorsion group as compared with other groups. The number of pre-antral and antral follicles and corpus luteum was significantly decreased in the torsion/detorsion group compared with the sham group, while treatment with O. europaea could enhance their numbers (P<0.05). The index of apoptosis and the number of atretic body in the ovarian tissue were significantly higher in the torsion/detorsion group compared with the sham group (P<0.05). The concentrations of glutathione peroxidase, estrogen, and superoxide dismutase as well as the mRNA expression of Bcl-2 were considerably diminished in the torsion/detorsion group while they were elevated in the torsion/detorsion+O. europaea group (P<0.05) compared with the torsion/detorsion group. The serum malondialdehyde level and the mRNA expression of Bax were markedly increased during ischemia, while treatment with O. europaea significantly diminished the increased concentrations of malondialdehyde and Bax level in the torsion/detorsion+O. europaea group (P<0.05). Conclusions: O. europaea extract can reduce the degree of tissue damage induced by oxidative stress and apoptosis in the ovary following ovarian ischemia/reperfusion.
基金supported by the National Natural Science Foundation of China,No.81771351the National Key R&D Program of China,No.2017YFA0105802+1 种基金the Joint Research Fund Liaoning-Shenyang National Laboratory for Materials Science,No.2019JH3/30100022the National Science Foundation for Post-doctoral Scientists of China,No.2018M641732(all to QA and LLW)。
文摘The functional properties of endogenous Schwann cells(SCs)during nerve repair are dynamic.Optimizing the functional properties of SCs at different stages of nerve repair may have therapeutic benefit in improving the repair of damaged nerves.Previous studies showed that miR-221-3p promotes the proliferation and migration of SCs,and miR-338-3p promotes the myelination of SCs.In this study,we established rat models of sciatic nerve injury by bridging the transected sciatic nerve with a silicone tube.We injected a miR-221 lentiviral vector system together with a doxycycline-inducible Tet-On miR-338 lentiviral vector system into the cavity of nerve conduits of nerve stumps to sequentially regulate the biological function of endogenous SCs at different stages of nerve regeneration.We found that the biological function of SCs was sequentially regulated,the diameter and density of myelinated axons were increased,the expression levels of NF200 and myelin basic protein were increased,and the function of injured peripheral nerve was improved using this system.miRNA Target Prediction Database prediction,Nanopore whole transcriptome sequencing,quantitative PCR,and dual luciferase reporter gene assay results predicted and verified Cdkn1b and Nrp1 as target genes of miR-221-3p and miR-338-3p,respectively,and their regulatory effects on SCs were confirmed in vitro.In conclusion,here we established a new method to enhance nerve regeneration through sequential regulation of biological functions of endogenous SCs,which establishes a new concept and model for the treatment of peripheral nerve injury.The findings from this study will provide direct guiding significance for clinical treatment of sciatic nerve injury.
基金funded by a grant provided from Endocrinology and Metabolism Research Center,Tehran University of Medical Sciences.
文摘The ultimate goal of tissue engineering is to design and fabricate functional human tissues that are similar to natural cells and are capable of regeneration.Preparation of cell aggregates is one of the important steps in 3D tissue engineering technology,particularly in organ printing.Two simple methods,hanging drop(HD)and conical tube(CT)were utilized to prepare cell aggregates.The size and viability of the aggregates obtained at different initial cell densities and pre-culture duration were compared.The proliferative ability of the cell aggregates and their ability to spread in culture plates were also investigated.In both methods,the optimum average size of the aggregates was less than 500μm.CT aggregates were smaller than HD aggregates.5,000 cells per drop HD aggregates showed a marked ability to attach and spread on the culture surface.The proliferative ability reduced when the initial cell density was increased.Comparing these methods,we found that the HD method having better size controlling ability as well as enhanced ability to maintain higher rates of viability,spreading,and proliferation.In conclusion,smaller HD aggregates might be a suitable choice as building blocks for making bioink particles in bioprinting technique.
基金funded by the National High Technology Research and Development Program of China ("863" Program,No.2012AA020905)the National Natural Science Foundation of China (No.81360194)the National Basic Research Program of China (973 program,No.2014CB542200)
文摘Given the anatomic complexity at the bifurcation point of a nerve trunk,enforced suturing between stumps can lead to misdirection of nerve axons,thereby resulting in adverse consequences.We assumed that Y-tube conduits injected with human umbilical cord stem cells could be an effective method to solve such problems,but studies focused on the best type of Y-tube conduit remain controversial.Therefore,the present study evaluated the applicability and efficacy of various types of Y-tube conduits containing human umbilical cord stem cells for treating rat femoral nerve defects on their bifurcation points.At 12 weeks after the bridging surgery that included treatment with different types of Y-tube conduits,there were no differences in quadriceps femoris muscle weight or femoral nerve ultrastructure.However,the Y-tube conduit group with longer branches and a short trunk resulted in a better outcome according to retrograde labeling and electrophysiological analysis.It can be concluded from the study that repairing a mixed nerve defect at its bifurcation point with Y-tube conduits,in particular those with long branches and a short trunk,is effective and results in good outcomes.
基金the grant of Science and Technology Bureau of Liaoning Province,No. 20041033
文摘Lead exposure induces decreased hippocampal N-methyI-D-aspartic acid （NMDA） receptor gene and protein expressions, which influences the molecular mechanisms of learning and memory. However, lead poisoning-induced differences in NMDA subunit expression, and the correlation of lead poisoning with learning and memory, remain poorly understood. The present study measured differences in expression of NMDA receptor subunits NR1, NR2A, and NR2B in memory-related brain regions of rats who underwent different doses of lead exposure. Results demonstrated decreased NR1, NR2A, and NR2B subunit expressions in some memory-related brain areas. The inhibitory effect of 4.8 mmol/L lead exposure on hippocampal NR2B was most significant, although NR2A expression also significantly decreased following 14.4 mmol/L lead exposure. There was no difference in NR1 expression following exposure to 〈 4.8 mmol/L lead, although the inhibitory effect of 19.6 mmol/L lead exposure was strongest for NR1 expression in the hippocampus. Inhibitory avoidance test results revealed that greater concentrations of lead exposure resulted in decreased learning and memory. Therefore, lead toxicity was dependent on NMDA receptor subunit composition, and NR1, NR2A, and NR2B expressions were associated with time and concentration of lead exposure.
基金supported by Universidad La Salle México and the Faculty of Engineering,Grant No.EC388-IMC-13/18CONACYT,Grant No.CB16RF_287927.
文摘This article presents the construction of scaffolds composed of polylactic acid(PLA)with different concentrations of hydroxyapatite(HA)by electrospinning,which were superficially modified with polypyrrole(PPy/I)by plasma polymerization.A preliminary study was conducted of the biological and mechanical behavior of the scaffolds when they were implanted in the back of rabbits for 30 days;bone cells differentiated from mesenchymal stem cells(MSCs)were used.The bone cell and scaffold structures were characterized by histological,immunohistochemical,and mechanical stress tests.Hematoxylin–eosin staining showed good tissue conformation.The immunohistochemical tests highlighted the presence of the main bone tissue proteins,such as collagen,osteocalcin,and osteopontin.The PLA/HA scaffolds were observed to exhibit cell adhesion and proliferation properties;however,the response was much better in the scaffolds that had a higher concentration of HA and that were coated with PPy/I.The results of the mechanical tests of the scaffolds indicated that the plasma treatment improved the adhesion and cell proliferation properties and contributed to the mechanical support,allowing the formation of neotissues with good viability of cell growth.
文摘The Klotho.(KL)gene is related to aging.In this study,SKL(secreted KL)and heparin were cross:linked to the acellular small intestinal submucosa(SIS).Based on this,small-diameter tissue engineered blood vessels(TEVs)were constructed.The role of SKL on improving the patency of TEVs through promoting cell adherence was investigated.The SIS membrane was cross linked with heparin and SKL,respectively,to prepare heparin group and SKL group artificial blood vessels.The CCK8 assay showed that SKL treatment promoted endothelial cells proliferation.Western blot showed that SKL upregulated the levels of FAK and RHOA.
文摘The presence of endometrial tissue outside of the uterine cavity is named endometriosis and is the most common gynecologic disorder in women. Determining the inhibitory effect of a Deforolimus on angiogenesis in a three-dimensional (3-D) culture of human endometrial stromal cells (hEnCs) in vitro. The important mechanism in the pathogenesis of endometriosis is angiogenesis, and deforolimus has been shown to have anti-angiogenic activity. This was an in vitro study of human endometrial stromal cells in 3-D culture of fibrin matrix. Endometrial stromal cells isolated and placed in a 3-D fibrin matrix culture system for angiogenesis with VEGF and inhibit angiogenesis by deforolimus. Finally these cells analyzed by CD31 antibodies. After 3 weeks, in cells treated with VEGF, endothelial cell branching was observed and rudimentary capillary-like structures formed. In the presence of 5μM of deforolimus, angiogenesis was reduced. The deforolimus were shown to be effective in inhibiting the mechanisms of angiogenesis.
文摘SARS-CoV-2 is a novel RNA coronavirus responsible of a deadly pandemic: the clinical illness COVID-19. With only one authorized drug for emergency use in critically ill patients: Remdesivir, there is not any other approved drug or vaccine yet with proven potential to overcome this infection. We exposed here many scientific evidences to support our novel idea that a macrolide, basically Clarithromycin, could be effective as a single agent for treatment and prophylaxis of COVID-19. Clarithromycin could change the history of this pandemic. It could reduce the costs of treatment and the potential adverse effects when combining more than one drug such as with Hydroxychloroquine. Clarithromycin treatment and prophylaxis as a single agent could be much more simple, safe and cheaper as giving Chloroquine or Hydroxychloroquine alone or in combination with Azithromycin as well as other therapeutic options.
文摘Human stromal stem cells derived from endometrium (hESCs) are a type of multipotent stromal cells of the proven ability to differentiate into osteogenic lineage. Thus, it was suggested that these cells may be used to repair skeletal defects. In this study, Human ESCs were extracted from female endometrium and harvested. Biomimetic gelatin/apatite (Gel/Ap) scaffolds with and without harvested cells were implanted in a Critical size calvarial defects in the cranial bone of adult male rat. To CT-Scan and Histological studies were performed to investigate the level of bone formation after 8 weeks of surgery. Results confirmed that the treated defects with the bare and hESCs grafted Gel/Ap scaffold showed significant bone formation and maturation in comparison with the control group.
