Quantum evaluation and therapeutic activity of (E)-N-(4-methoxyphenyl)-2-(4-(3-oxo-3-phenylprop-1-en-1-yl) phenoxy)acetamide and its modified derivatives against EGFR and VEGFR-2 in the treatment of triple-negative cancer via in silico approach.

The most dangerous subtype of breast cancer, triple-negative breast cancer (TNBC), accounts for 25% of all breast cancer-related deaths and 15% of all breast cancer cases. TNBC is distinguished by the lack of immunohistochemical expression of HER2, progesterone receptors, or oestrogen receptors. Although it has been reported that upregulation of EGFR and VEGFR-2 is associated with TNBC progression, no proven effective targeted therapy exists at this time. We used structural bioinformatics methods, including density functional theory, molecular docking, molecular dynamic simulation, pharmacokinetic and drug-likeness models, to identify promising EGFR/VEGFR-2 inhibitors from N-(4-methoxyphenyl)-2-[4-(3-oxo-3-phenylprop-1-en-1-yl) phenoxy] acetamide and six of its modified derivatives in light of the lack of effective targets inhibitor Version 14 of Spartan software was used to analyse density functional theory. The Schrodinger software suite 2018's Maestro interface was used for the molecular docking analysis, and the admetSAR and swissADME servers were used for drug-likeness and absorption, distribution, metabolism, excretion, and toxicity. All of the compounds showed strong electronic characteristics. Additionally, all of the tested compounds met the ADMET and drug-likeness requirements without a single instance of Lipinski's rule of five violations. Additionally, the molecules' levels of affinity for the target proteins varied. The highest binding affinities were demonstrated by the MOLb-VEGFR-2 complex (- 9.925 kcal/mol) and the MOLg-EGFR complex (- 5.032 kcal/mol). The interaction of the molecules in the domain of the EGFR and VEGFR-2 receptors was also better understood through molecular dynamic simulation of the complex.

Discovery of Potential Phytochemicals from Carica papaya Targeting BRCA-1 in Breast Cancer Treatment.

The BRCA1 and BRCA2 are genes that encode a protein that ensures the integrity of DNA and prevents the unregulated cells from proliferating. Mutations in the sequence of these genes are associated with the birth of inherited breast cancers. The research for possible human breast cancer treatment remains a vital step in the drug development process. In this study, in silico investigations involving a computational method for the discovery of active phytochemicals from Carica papaya against the BRCA-1 gene were carried out. The in silico studies for these phytochemicals datasets as BRCA-1 breast cancer therapeutic agents showed promising results through pharmacokinetics and pharmacodynamics studies. The Carica papaya compounds were found to follow the rule of five and have good bioavailability. The ADMET and drug-likeness screening score of the identified ligands also recognized their potential as a promising drug candidate against BRCA-1 while the DFT also confirm better biological and chemical reactivity of Carica papaya compounds with excellent intra-molecular charge transfer between electron donor and electron acceptor site. The results of the molecular docking provided useful information on possible target-lead interactions, demonstrating that the newly developed leads showed a high affinity for BRCA-1 targets and might be investigated for further research.

Discovery of Small Molecule PARKIN Activator from Antipsychotic/Anti-neuropsychiatric Drugs as Therapeutics for PD: an In Silico Repurposing Approach.

Although there is presently no cure for Parkinson's disease (PD), the available therapies are only able to lessen symptoms and preserve the quality of life. Around 10 million people globally had PD as of 2020. The widely used standard drug has recently been revealed to have several negative effects. Additionally, there is a dearth of innovative compounds entering the market as a result of subpar ADMET characteristics. Drug repurposing provides a chance to reenergize the sluggish drug discovery process by identifying new applications for already-approved medications. As this strategy offers a practical way to speed up the process of developing alternative medications for PD. This study used a computer-aided technique to select therapeutic agent(s) from FDA-approved neuropsychiatric/psychotic drugs that can be adopted in the treatment of Parkinson's disease. In the current work, a computational approach via molecular docking, density functional theory (DFT), and pharmacokinetics were used to identify possible (anti)neuropsychiatric/psychotic medications for the treatment of PD. By using molecular docking, about eight (anti)neuropsychiatric/psychotic medications were tested against PARKIN, a key protein in PD. Based on the docking score, the best ligand in the trial was determined. The top hits were compared to the reference ligand levodopa (L-DOPA). A large proportion of the drugs displayed binding affinity that was relatively higher than L-DOPA. Also, DFT analysis confirms the ligand-receptor interactions and the molecular charge transfer. All the compounds were found to obey Lipinski's rule with acceptable pharmacokinetic properties. The current study has revealed the effectiveness of antineuropsychiatric/antipsychotic drugs against PARKIN in the treatment of PD and lumateperone was revealed to be the most promising candidate interacting with PARKIN.

A Meta-analysis on the Effectiveness of Extracellular Vesicles as Nanosystems for Targeted Delivery of Anticancer Drugs.

While the efficacy of anticancer drugs is hampered by low bioavailability and systemic toxicity, the uncertainty remains whether encapsulation of these drugs into natural nanovesicles such as extracellular vesicles (EVs) could improve controlled drug release and efficacy for targeted tumor therapy. Thus, we performed a meta-analysis for studies reporting the efficacy of EVs as nanosystems to deliver drugs and nucleic acid, protein, and virus (NPV) to tumors using the random-effects model. The electronic search of articles was conducted through Cochrane, PubMed, Scopus, Science Direct, and Clinical Trials Registry from inception up till September 2022. The pooled summary estimate and 95% confidence interval of tumor growth inhibition, survival, and tumor targeting were obtained to assess the efficacy. The search yielded a total of 119 studies that met the inclusion criteria having only 1 clinical study. It was observed that the drug-loaded EV was more efficacious than the free drug in reducing tumor volume and weight with the standardized mean difference (SMD) of -1.99 (95% CI: -2.36, -1.63; p < 0.00001) and -2.12 (95% CI: -2.48, -1.77; p < 0.00001). Similarly, the mean estimate of tumor volume and weight for NPV were the following: SMD: -2.30, 95% CI: -3.03, -1.58; p < 0.00001 and SMD: -2.05, 95% CI: -2.79, -1.30; p < 0.00001. Treatment of tumors with EV-loaded anticancer agents also prolonged survival (HR: 0.15, 95% CI: 0.10, 0.22, p < 0.00001). Furthermore, EVs significantly delivered drugs to tumors as revealed by the higher concentration at the tumor site (SMD: -2.73, 95% CI: -3.77, -1.69; p < 0.00001). This meta-analysis revealed that EV-loaded drugs and NPV performed significantly better in tumor growth inhibition with improved survival than the free anticancer agents, suggesting EVs as safe nanoplatforms for targeted tumor therapy.

Exosomes as Delivery Systems for Targeted Tumour Therapy: A Systematic Review and Meta-analysis of In vitro Studies.

BACKGROUND: Delivery systems with low immunogenicity and toxicity are believed to enhance the efficacy of specific targeted drug delivery to cancer cells. Exosomes are potential natural nanosystems that can enhance the delivery of therapeutic agents for targeted cancer therapy. OBJECTIVE: This study provides a precise effect size of exosomes as nanovesicles for in vitro delivery of anticancer agents. METHODS: In this systematic review and meta-analysis, the efficacy of exosomes as nanocarriers for the delivery of therapeutic molecules was investigated using the random-effects model. We did comprehensive literature searches through CINAHL, Cochrane, PubMed, Scopus, and Science Direct of in vitro studies that reported exosomes as delivery systems for cancer therapy. RESULTS: After the screening of eligible articles, a total of 50 studies were enrolled for the metaanalysis. The results showed that cancer cells treated with exosome-loaded anticancer agents for at least 6 h significantly decreased cell viability and increased cytotoxicity with the standardized mean difference (SMD) of -1.47 (-2.18, -0.76; (p<0.0001) and -1.66 (-2.71, -0.61; p<0.002). Exosomes effectively delivered drugs and exogenous miRNAs, siRNAs, viruses, and enzymes to cancer cells in vitro. CONCLUSION: This meta-analysis provides evidence of exosomes as efficient nanocarriers for the delivery of anticancer drugs.

Antioxidant-Rich Nutraceutical as a Therapeutic Strategy for Sickle Cell Disease.

Sickle cell disease (SCD) is a genetically inherited disease in which the "SS" individual possesses two copies of the abnormal beta-globin gene. This disease is one of the most dominant genetic diseases in the world. SCD is marked by the propensity of red cell hemoglobin to polymerize and distort the red cell from a biconcave disk shape into a sickle shape, resulting in a typical vaso-occlusive episode and accelerated hemolysis. Plants are rich sources of bioactive compounds that are promising anti-sickling agents to scavenge free radicals, thereby ensuring oxidative balance. The current review highlights the potential therapeutic benefits of antioxidant-rich nutraceutical in the treatment and management of sickle cell disease. The anti-sickling potential of nutraceutical is attributed to the presence of antioxidant bioactive chemicals such as alkaloids, polyphenols, vitamins, and minerals, which acts as scavengers of free radicals that prevent oxidative damage of the hemoglobin and prevent hemolysis, facilitating longer erythrocyte lifespan. The challenges of current therapies for SCD and future directions are also discussed.KEY TEACHING POINTSSickle cell disease is a genetically inherited disease in which SS individuals possess two copies of the abnormal beta-globin gene.Oxidative stress contributes to the pathophysiology of secondary dysfunction in sickle cell patients.Antioxidants can play a vital role in maintaining a balance between oxidant and antioxidant defense systems.Nutraceutical rich in antioxidants such as alkaloids, polyphenols, vitamins, and minerals is potential therapeutic agents for sickle cell disease.An antioxidant-rich nutraceutical may act to reduce vaso-occlusive crises.

Efficacy of stem cell secretome in the treatment of traumatic brain injury: A systematic review and meta-analysis of preclinical studies.

Traumatic brain injury (TBI) remains a public health challenge and represents one of the major contributors to disability and mortality worldwide among all trauma-related injuries. This study aimed to determine a precise effect size of secretome intervention in TBI. We performed a systematic literature search through Cochrane, MEDLINE Complete, PubMed and Scopus databases for articles published until June 2021. The search terms used include cells OR stem cells OR mesenchymal stem cells AND secretome OR conditioned medium OR extracellular vesicles OR exosomes OR microvesicles AND traumatic brain injury OR head injury. Neurological deficits and neuroinflammation were the outcome measures assessed after the intervention. Thirty-one (31) studies involving mouse, rat and swine were enrolled for the meta-analysis. Secretome significantly improved structural and functional recovery when compared with control. The mean effect sizes were as follows: modified neurological severity score (mNSS) (-2.65, 95% CI: -3.42, -1.87, p < 0.00001), impact size (-3.02 mm3, 95% CI: -4.97, -1.08, p = 0.002) and latency to platform (-17.20 s, 95% CI: -23.91, -10.50, p < 0.00001). Similarly, intervention with secretome reduced neuroinflammation after TBI. The results of meta-regression showed that the source of secretome, TBI models and duration of follow-up did not influence the mNSS. Furthermore, the methodological quality of the studies was moderate as shown by the risk of bias assessment. Publication bias was observed for the mNSS. This meta-analysis provides preclinical evidence of secretome intervention in TBI, suggesting that it can be explored as a therapeutic agent for TBI and other neurological disorders in humans.

Early marriage and teenage pregnancy: The unspoken consequences of COVID-19 pandemic in Nigeria.

Early marriage and its sad consequences to the girl child and socio-economic development of the nation has been an age-long issue being advocated against in many parts of Nigeria. At the onset of COVID-19, the teeming efforts to curb this issue almost got jeopardized with harsh economic situations in many households due to the lockdown and the willingness to marry off their girls to reduce this burden. Closure of schools and cases of sexual gender based violence also impacted the prevalence of early marriage during the pandemic in Nigeria. We also argue in this commentary that the pandemic has so much impacted on programs aimed at ending early marriage in the nation. Therefore, if serious and concerted efforts are not taken by relevant stakeholders, more girls will be at risk of early marriage and teenage pregnancy with their related health consequences. They will also be left behind in fulfilling their potentials and their aspirations cut off with early marriage, thus sustainable development cannot be achieved.

A systematic review with meta-analysis on the antihypertensive efficacy of Nigerian medicinal plants.

ETHNOPHARMACOLOGICAL RELEVANCE: Despite the promising effects of herbal preparations in lowering blood pressure (BP), hypertension remains a major clinical challenge in Nigeria. The BP-lowering effects of medicinal plants are due to the presence of bioactive compounds. AIM OF THE STUDY: This meta-analysis presents a precise estimate of the therapeutic benefits of medicinal plants utilized in Nigeria for the management of hypertension in animals and humans. METHODS: A systematic literature search was performed through Cochrane, PubMed, Science Direct and Scopus databases from inception until February 28, 2021 using search terms related to randomized controlled trials of Nigerian medicinal plants for hypertension. Additional studies were identified through manual search. BP was the main outcome that was measured after the intervention. Meta-analysis was performed using the Review Manager and Meta-Essential. RESULTS: Nineteen trials comprising of 16 preclinical and 3 clinical studies were enrolled for the meta-analysis. A total number of 16 plants was identified of which H. sabdariffa was the highest reported plant. The plant extracts significantly lowered the systolic blood pressure (SBP) and diastolic blood pressure (DBP) of the hypertensive subjects compared to control. Weighted mean difference (WMD) for SBP (-43.60 mmHg, 95% CI: -63.18, -24.01; p<0.0001) and DBP (-29.50 mmHg, 95 CI: -43.66, -15.34; p<0.0001) was observed for the preclinical studies. For clinical trials, the WMD was -13.98 mmHg, 95 CI: -19.08, -8.88; p<0.00001 for SBP and -10.00 mmHg, 95 CI: -12.22, -7.78; p<0.00001 for DBP. High heterogeneity was observed for the outcome measures of preclinical studies, but not for the clinical studies. The observed substantial heterogeneity in preclinical studies may be linked to methodological shortcomings as evidenced by the results of the risk of bias assessment. There was no evidence of publication bias in animal trials for BP using the funnel plot and Egger's regression test (SBP, p=0.239 and DBP, p=0.112). CONCLUSIONS: This study provides evidence of medicinal preparations for the treatment of hypertension. A well-conducted trial with methodological rigour and a longer duration of follow-up is required for their effective clinical utilization.

Optimization of Protocol for Isolation of Chondrocytes from Human Articular Cartilage.

OBJECTIVE: Cartilage tissue engineering has evolved as one of the therapeutic strategies for cartilage defect, which relies on a large number of viable chondrocytes. Because of limited availability of cartilage and low chondrocytes yield from cartilage, the need for an improve isolation protocol for maximum yield of viable cells is a key to achieving successful clinical constructs. This study optimizes and compares different protocols for isolation of chondrocytes from cartilage. DESIGN: We employed enzymatic digestion of cartilage using collagenase II and trypsin. The chondrocytes yield, growth kinetics, aggrecan, and collagen type 2 (COL2) expression were evaluated. Collagen type 1 (COL1) mRNA expression was assessed to monitor the possibility of chondrocytes dedifferentiation. RESULTS: Chondrocyte yield per gram of cartilage was significantly higher (P < 0.05) using collagenase II in Hank's balanced salt solution (HBSS) compared with 0.25% trypsin. The number of chondrocyte yield per gram was higher in cartilage digested with collagenase in HBSS compared with Dulbecco's modified Eagle medium/F12; however, the difference was not statistically significant. Chondrocytes seeded at lower densities had shorter population doubling time compared to those seeded at higher density. Protein and gene expression of chondrocyte phenotype indicates the expression of aggrecan and COL2. The expression of COL1 was significantly increased (P < 0.05) in passage 3 compared with primary chondrocytes. The mRNA expression of chondrocyte phenotype was similar in primary and passaged one cells. CONCLUSIONS: Collagenase in HBSS yield the highest number of viable chondrocytes and the isolated cells expressed chondrocyte phenotype. This protocol can be employed to generate large number of viable chondrocytes, particularly with limited cartilage biopsies.

Effect of natron administration on the antioxidant status and lipid profile of rats.

Natron consumption has been implicated in the pathogenesis of peripartum cardiomyopathy. This work evaluates the effect of natron on the antioxidant status and lipid profile of postpartum rats administered graded doses of natron for four consecutive weeks. After treatment, the rats were assessed for antioxidant status, malondialdehyde level, and lipid profile. The results revealed that natron caused a significant decrease (P Ë‚ 0.05) in the activity of catalase in rats administered with 300 mg/kg of natron compared to control. The activities of superoxide dismutase and glutathione peroxidase decreased in a dose-dependent manner; however, the difference was not statistically significant when compared with control. Serum levels of antioxidant minerals were also significantly decreased (P Ë‚ 0.05) at higher doses of natron in comparison to control. There was a significant increase (P < 0.05) in the malondialdehyde level in rats administered with 200 and 300 mg/kg of natron when compared with control. Natron at higher doses caused a significant increase (P Ë‚ 0.05) in the level of the lipid profile parameters except for high-density lipoprotein-cholesterol that decrease significantly (P Ë‚ 0.05). This study demonstrated that the administration of natron at high doses induced dyslipidemia and oxidative stress in postpartum rats. PRACTICAL APPLICATION: This research reports the implication of a high intake of natron to health and to establish the relationship between natron intake and peripartum cardiomyopathy (PPCM) using an animal model. Natron has health benefits; however, its consumption at high doses should be discouraged as it can lead to oxidative stress (OS) and dyslipidemia. The results suggest that OS due to natron may contribute to the pathogenesis of PPCM. A high concentration of natron can be used to induce an animal model of PPCM, which would be of practical application in studying the molecular basis and possible discovery of therapeutics for the disease.

Protective effects of stem cells from human exfoliated deciduous teeth derived conditioned medium on osteoarthritic chondrocytes.

Treatment of osteoarthritis (OA) is still a major clinical challenge due to the limited inherent healing capacity of cartilage. Recent studies utilising stem cells suggest that the therapeutic benefits of these cells are mediated through the paracrine mechanism of bioactive molecules. The present study evaluates the regenerative effect of stem cells from human exfoliated deciduous teeth (SHED) conditioned medium (CM) on OA chondrocytes. The CM was collected after the SHED were cultured in serum-free medium (SFM) for 48 or 72 h and the cells were characterised by the expression of MSC and pluripotency markers. Chondrocytes were stimulated with interleukin-1ß and treated with the CM. Subsequently, the expression of aggrecan, collagen type 2 (COL 2), matrix metalloproteinase-13 (MMP-13), nuclear factor-kB (NF-kB) and the level of inflammatory and anti-inflammatory markers were evaluated. SHED expressed mesenchymal stromal cell surface proteins but were negative for haematopoietic markers. SHED also showed protein expression of NANOG, OCT4 and SOX2 with differential subcellular localisation. Treatment of OA chondrocytes with CM enhanced anti-inflammation compared to control cells treated with SFM. Furthermore, the expression of MMP-13 and NF-kB was significantly downregulated in stimulated chondrocytes incubated in CM. The study also revealed that CM increased the expression of aggrecan and COL 2 in OA chondrocytes compared to SFM control. Both CM regenerate extracellular matrix proteins and mitigate increased MMP-13 expression through inhibition of NF-kB in OA chondrocytes due to the presence of bioactive molecules. The study underscores the potential of CM for OA treatment.

Therapeutic efficacy of mesenchymal stromal cells and secretome in pulmonary arterial hypertension: A systematic review and meta-analysis.

Mesenchymal stromal cells (MSCs) and secretome are promising therapies for pulmonary arterial hypertension (PAH). This meta-analysis aimed to provide a precise estimate and compare the therapeutic efficacy of MSC and secretome in PAH. We searched six databases (CINAHL, Cochrane, Ovid Medline, PubMed, Science Direct and Scopus) until December 2018 using search terms related to MSCs, secretome and PAH. Twenty-three studies were included for the meta-analysis. The effect size of pulmonary hemodynamics and right ventricular hypertrophy markers was estimated using random effects model. MSCs and secretome significantly improved pulmonary hemodynamics and right ventricular hypertrophy compared to control. Comparison between MSCs and secretome indicate no significant difference in reducing right ventricular systolic pressure (RVSP) and medial wall thickening (MWT). However, treatment of PAH with secretome significantly improved mean pulmonary arterial pressure (mPAP) (p = 0.018) and right ventricular/left ventricular + septum (RV/LV+S) (p = 0.017) better than MSCs. Meta-regression shows that cell type (p = 0.034) is a predictor of MSCs to reduce RVSP in PAH. Similarly, the effect of secretome on MWT was significantly (p = 0.011) better at 4 weeks compared to 2 weeks of intervention. The overall risk of bias ranges from low to moderate; however, some of the essential elements required in reports of animal trials were not reported. There was evidence of publication bias for RV/LV+S and MWT, but not RVSP. This meta-analysis provides evidence of the therapeutic benefits of MSCs and secretome in PAH and the effect of secretome was similar or superior to MSCs.

Mesenchymal stromal cell secretome as a therapeutic strategy for traumatic brain injury.

Traumatic brain injury (TBI) is a global health problem that is a common cause of disability and mortality. Despite the availability of many treatment options, none is capable of restoring functional and structural recovery of the damaged brain. Both the results of preclinical and clinical studies suggest the use of mesenchymal stromal cells (MSCs) as a therapeutic strategy for structural and functional recovery in TBI. However, recent evidence shows that the neuroprotective potential of MSCs is due to multiple secretions of bioactive molecules that modulate tissue microenvironment for tissue repair and regeneration. The results of preclinical studies indicate the therapeutic benefits of MSC secretome in TBI. Soluble bioactive molecules and extracellular vesicles are the various factors secreted by MSCs that can induce neurogenesis, angiogenesis, neovascularization, and anti-inflammatory activities. This review highlights the neuroprotective effect of MSC secretome for the treatment of TBI. In addition, the possible challenges of secretome as biotherapeutics are identified and how some of the issues raised could be overcome for effective clinical application are also discussed.

Effect of protocatechuic acid-layered double hydroxide nanoparticles on diethylnitrosamine/phenobarbital-induced hepatocellular carcinoma in mice.

Researchers investigating cancer chemotherapy and management continue to search for agents that selectively kill malignant cells and leave healthy neighboring cells intact. Natural products provide relevant resources for anti-cancer drug discovery. However, the physicochemical properties of these compounds limit their efficient uptake and bioavailability. We introduced a nanocarrier system, namely, zinc-aluminum-layered double hydroxide (ZnAl-LDH) intercalated with protocatechuic acid. In this study, the efficacy and toxicity of protocatechuic acid intercalated in zinc aluminum-layered double hydroxide nanoparticles (PCA-ZnAl) against diethylnitrosamine/phenobarbital (DEN/PB)-induced hepatocellular carcinoma (HCC) in BALB/c mice was evaluated. HCC in male mice was induced by a single-dose intraperitoneal administration of DEN and was promoted by the introduction of PB via drinking water for 12 weeks. HCC induction was confirmed after the DEN/PB introduction period by measurement of the elevated level of serum α-feto protein (AFP). The results showed that the level of α-fetoprotein was significantly reduced in PCA-ZnAl (350±43.90 ng/mL), doxorubicin (DOX) (290±20.52 ng/mL) and ZnAl-LDH (390±19.65 ng/mL) treated animals compared to HCC mice treated with normal saline (580.4± 52.04 ng/mL). Superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) levels were significantly increased, whereas the level of lipid peroxidation was significantly decreased in HCC mice treated with DOX, PCA-ZnAl and ZnAl-LDH compared with those in HCC mice treated with saline. Restoration of hepatocyte morphology was observed following treatment that was comparable to that in the normal control group. Deterioration of hepatic cells and a significant increase of aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP) were observed in the cancer-induced untreated group compared with that in the groups treated with nanoparticles. The histopathological features of the liver obtained from PCA-ZnAl-treated mice showed a uniform size with a similar distribution of the nuclear-cytoplasmic ratio and nucleus centrally located in the cytoplasm, similar to the normal liver cells. The results underscored the potential of PCA-ZnAl for the treatment of hepatocellular carcinoma.

Comparative efficacy of stem cells and secretome in articular cartilage regeneration: a systematic review and meta-analysis.

Articular cartilage defect remains the most challenging joint disease due to limited intrinsic healing capacity of the cartilage that most often progresses to osteoarthritis. In recent years, stem cell therapy has evolved as therapeutic strategies for articular cartilage regeneration. However, a number of studies have shown that therapeutic efficacy of stem cell transplantation is attributed to multiple secreted factors that modulate the surrounding milieu to evoke reparative processes. This systematic review and meta-analysis aim to evaluate and compare the therapeutic efficacy of stem cell and secretome in articular cartilage regeneration in animal models. We systematically searched the PubMed, CINAHL, Cochrane Library, Ovid Medline and Scopus databases until August 2017 using search terms related to stem cells, cartilage regeneration and animals. A random effect meta-analysis of the included studies was performed to assess the treatment effects on new cartilage formation on an absolute score of 0-100% scale. Subgroup analyses were also performed by sorting studies independently based on similar characteristics. The pooled analysis of 59 studies that utilized stem cells significantly improved new cartilage formation by 25.99% as compared with control. Similarly, the secretome also significantly increased cartilage regeneration by 26.08% in comparison to the control. Subgroup analyses revealed no significant difference in the effect of stem cells in new cartilage formation. However, there was a significant decline in the effect of stem cells in articular cartilage regeneration during long-term follow-up, suggesting that the duration of follow-up is a predictor of new cartilage formation. Secretome has shown a similar effect to stem cells in new cartilage formation. The risk of bias assessment showed poor reporting for most studies thereby limiting the actual risk of bias assessment. The present study suggests that both stem cells and secretome interventions improve cartilage regeneration in animal trials. Graphical abstract ᅟ.

Biochemical and histological changes in the heart of post-partum rats exposed to Natron.

BACKGROUND: The customary puerperal practice of Natron consumption has been identified as one of the predisposing factors in the etiology of peripartum cardiomyopathy (PPCM). This study was designed to investigate the effect of Natron in postpartum Wistar albino rats. METHODS: A total of 30 postpartum Wistar rats were exposed to different doses (50mg/kg, 100mg/kg, 200mg/kg and 300mg/kg) of Natron for 28days. After the treatment, we carried out biochemical analyses and histological evaluations of kidney, liver and heart. RESULTS: The study revealed that the exposure of postpartum rats to 100mg/kg of Natron and above significantly (p<0.05) increase the cardiac markers; myoglobin, creatine kinase-MB, troponin I and T as compared with control. The result of liver function indicated no significant difference in alanine aminotransferase, aspartate aminotransferase, gamma-glutamyltransferase, albumin and total protein of the Natron treated groups as compared with control. However, at higher doses, the levels of total protein, globulin and alkaline phosphatase activity were significantly increased in comparison to the control. There was no significant difference in the kidney function markers of the treatment groups as compared with control. Histological examinations revealed no changes in the kidney of the treated groups. Mild portal triaditis was observed in the liver of the treated rats. The heart of the rats administered ≥100mg/kg of Natron showed myocyte hypertrophy. CONCLUSION: The study demonstrated that the administration of Natron for 28days caused changes in the heart of postpartum rats and thus may contribute to the pathogenesis of PPCM.

Computational investigation of TGF-ß receptor inhibitors for treatment of idiopathic pulmonary fibrosis: Field-based QSAR model and molecular dynamics simulation.

The discovery of drugs relevant to transforming growth factor ß (TGF-ß) receptor inhibitors have been considered as a considerable challenge during therapy idiopathic pulmonary fibrosis diseases. For the first time, herein we illustrate a field-based quantitative structure-activity relationship (QSAR) model and molecular dynamics (MD) simulations for novel 7-substituted-pyrazolo [4, 3-b] pyridine derivatives with biological activity for the TGF-ß receptor, with an attempt of elucidating the 3D structural features that are essential for the activity. Results demonstrate that the field-based model (Q2 = 0.548, R2training = 0.840, R2test = 0.750) are acceptable with good predictive capabilities. In addition, MD studies were also carried out on the training set with the aim of exploring their binding modes in the active pocket of TGF-ß receptor, resulting in some of the crucial structural fragments which are responsible for inhibitory activity. Therefore, we summarized the following features required for TGF-ß receptor inhibition: electronegative in region1, bulky groups in region2 and smaller groups in region3. Based on the model and related information, we hope the above information provides an important insight for understanding the interactions of the inhibitors and TGF-ß receptor, which may be useful in discovering novel potent inhibitors.

Regenerative potential of secretome from dental stem cells: a systematic review of preclinical studies.

Injury to tissues is a major clinical challenge due to the limited regenerative capacity of endogenous cells. Stem cell therapy is evolving rapidly as an alternative for tissue regeneration. However, increasing evidence suggests that the regenerative ability of stem cells is mainly mediated by paracrine actions of secretome that are generally secreted by the cells. We aimed to systematically evaluate the efficacy of dental stem cell (DSC)-conditioned medium in in vivo animal models of various tissue defects. A total of 15 eligible studies was included by searching Pubmed, Scopus and Medline databases up to August 2017. The risk of bias was assessed using the Systematic Review Centre for Laboratory Animal Experimentation risk of bias tool. Of 15 studies, seven reported the therapeutic benefit of the conditioned medium on neurological diseases and three reported on joint/bone-related defects. Two interventions were on liver diseases, whereas the remaining three addressed myocardial infarction and reperfusion, lung injury and diabetes. Nine studies were performed using mouse models and the remaining six studies used rat models. The methodological quality of the studies was low, as most of the key elements required in reports of preclinical studies were not reported. The findings of this review suggested that conditioned medium from DSCs improved tissue regeneration and functional recovery. This current review strengthens the therapeutic benefit of cell-free product for tissue repair in animal models. A well-planned study utilizing validated outcome measures and long-term safety studies are required for possible translation to clinical trials.

Circulating miR-92a, miR-143 and miR-342 in Plasma are Novel Potential Biomarkers for Acute Myeloid Leukemia.

MicroRNAs (miRNAs) are small non-coding RNAs that function as post-transcriptional gene expression regulators. The expression profiling of miRNAs has already entered into cancer clinics as diagnostic and prognostic biomarkers to assess tumor initiation, progression and response to treatment in cancer patients. Recent studies have opened the way for the use of circulating miRNAs as non-invasive diagnosis and prognosis of Acute myeloid leukemia (AML). The aim of this study was to identify plasma miR-92a, miR-143 and miR-342 expression signatures in AML patients to introduce new markers for establishing AML diagnosis and prognosis. Blood samples were collected from 65 AML patients and 50 controls. The expression of three target miRNAs (miR-92a, miR-143 and miR-342) was measured using quantitative real-time PCR method. Plasma levels of miR-92a, miR-143 and miR-342 were significantly lower in AML patients in comparison with control group. Receiver operator characteristic (ROC) analysis revealed that the sensitivity and specificity values of miR-92a were 81.5% and 94%, respectively, with a cut-off value of 0.704. The sensitivity and specificity values of miR-143 were 87.7% and 80%, respectively, with a cut-off value of 0.65. The sensitivity and specificity values of miR-342 were 75.4% and 90%, respectively, with a cut-off value of 0.479. Our findings suggest that plasma miR-92a, miR-143 and miR-342 could be promising novel circulating biomarkers in clinical detection of AML.