Biology
Human Umbilical Cord Mesenchymal Stem Cells Alleviate Chronic Salpingitis by Modulating Macrophage-Associated Inflammatory Factors
Introduction: Mesenchymal stem cells (MSCs) have been widely studied because of their established anti-inflammatory properties. During chronic salpingitis (CS) infiltrated macrophages have vital roles in inflammation and tissue remodeling. Methods: We employed the type of MSCs human umbilical cord (huc) MSCs in an experimental CS model and therapeutic efficacy was assessed. hucMSCs exerted this therapeutic effect by regulating macrophage function. To verify the regulatory effects of hucMSCs on the macrophage macrophage line RAW264.7 markers were analyzed under LPS stimulation with or without co-culturing with hucMSCs for 12h and 24h. In addition flow cytometry analysis was applied to reveal the interaction of co-culture. For animal studies CS was induced by the MoPn strain Chlamydia trachomatis (CT) hucMSCs were intravaginally injected in the CS and we analyzed the infiltrated macrophage by immunofluorescence. Results: We found the markers IL-10 was markedly increased and IL-1β caspase-1 was notably downregulated after co-culturing with hucMSCs by RT-PCR. hucMSCs promote macrophage line RAW264.7 apoptosis. We also found that hucMSCs treatment can alleviate CS by decreasing the mRNA expression of IL-1β caspase-1 and MCP-1 in the tubal tissue by RT-PCR and decreasing the protein expression of IL-1β caspase-1 and TGF-β by western blotting. Conclusion: These results suggest that macrophage function may be related to the immune-modulating characteristics of hucMSCs that contribute to CS.
Enhancing the Regenerative Potential of Adipose-Derived Mesenchymal Stem Cells Through TLR4-Mediated Signaling
Introduction: Toll-like receptor 4 (TLR4) is a receptor that traditionally plays an important role in immunomodulation (regulation of the immune system) and the initiation of proinflammatory responses. TLR4 is used in the body to recognize molecular patterns of pathogens or damaged cells from outside. However in recent years it has also become clear that TLR4 can affect the immune system and the function of stem cells especially mesenchymal stem cells. Therefore understanding how TLR4 signaling works at the cellular and molecular level and using this knowledge in regenerative medicine could be potentially useful especially in the treatment of adipose- derived mesenchymal stem cells (ADMSCs). How these cells can use TLR4 signaling when used to increase their regenerative potential and repair tissues is an area of research. Aims: This study aims to elucidate the multifaceted role of TLR4-mediated signaling in ADMSCs. Methods: Employing a comprehensive set of assays including MTT for cell viability flow cytometry for surface marker expression and gene expression analysis we demonstrate that TLR4 activation significantly modulates key aspects of ADMSC biology. Specifically TLR4 signaling was found to regulate ADMSCs proliferation surface marker expression and regenerative capacity in a dose- and time-dependent manner. Furthermore TLR4 activation conferred cytoprotective effects against Doxorubicin (DOX)-induced cellular apoptosis. Results: These findings suggest that TLR4 signaling could be used to enhance the regenerative abilities of ADMSCs and enable ADMSC-based therapies to be used more effectively for tissue engineering and therapeutic purposes. Conclusion: However it is important to note that research in this area needs more details and clinical studies.
Enhancing Spermatogenesis in Non-obstructive Azoospermia Through Mesenchymal Stem Cell Therapy22
Stem cells hold great promise as novel and encouraging therapeutic tools in the treatment of degenerative disorders due to their differentiation potential while maintaining the capability to self-renewal and their unlimited ability to divide and regenerate tissue. A variety of different types of stem cells can be used in cell therapy. Among these mesenchymal stem cell (MSC) therapy has gradually established itself as a novel method for treating damaged tissues that need restoration and renewal. Male infertility is an important health challenge affecting approximately 8-12% of people around the world. This abnormality can be caused by primary congenital acquired or idiopathic reasons. Men with no sperm in their semen have a condition called azoospermia caused by non-obstructive (NOA) causes and post-testicular obstructive causes. Accumulating evidence has shown that various types of MSCs can differentiate into germ cells and improve spermatogenesis in the seminiferous tubules of animal models. In addition recent studies in animal models have exhibited that extracellular vesicles derived from MSCs can stimulate the progression of spermatogenesis and germ cell regeneration in the recipient testes. In spite of the fact that various improvements have been made in the treatment of azoospermia disorder in animal models by MSC or their extracellular vesicles no clinical trials have been carried out to test their therapeutic effect on the NOA. In this review we summarize the potential of MSC transplantation for treating infertility caused by NOA.
Evaluation of Pancreatic β-cell Differentiation Efficiency of Human iPSC Lines for Clinical Use2212
Background: Transplantation of pancreatic β-cells generated from human induced pluripotent stem cells (hiPSCs) has great potential as a root treatment for type 1 diabetes. However their current level of efficiency to differentiate into β-cells is still not at par for clinical use. Previous research has shown that differentiation efficiency varies among human embryonic stem cells and mouse-induced pluripotent stem cell lines. Therefore selecting a suitable cell line for efficient induction into desired tissues and organs is crucial. Methods: In this study we have evaluated the efficiency of 15 hiPSC lines available for clinical use to differentiate into pancreatic β-cells. Results: Our investigation has revealed induction efficiency to differ among the hiPSC lines even when derived from the same donor. Among the hiPSC lines tested the 16A01 cell line exhibited the highest Insulin expression and low Glucagon expression suggesting that this cell line is suitable for differentiation into β-cells. Conclusion: Our study has demonstrated the importance of selecting a suitable hiPSC line for effective differentiation into β-cells.
Mechanisms of Stem Cells and Their Secreted Exosomes in the Treatment of Autoimmune Diseases
Stem cells play a therapeutic role in many diseases by virtue of their strong self-renewal and differentiation abilities especially in the treatment of autoimmune diseases. At present the mechanism of the stem cell treatment of autoimmune diseases mainly relies on their immune regulation ability regulating the number and function of auxiliary cells anti-inflammatory factors and proinflammatory factors in patients to reduce inflammation. On the other hand the stem cell- derived secretory body has weak immunogenicity and low molecular weight can target the site of injury and can extend the length of its active time in the patient after combining it with the composite material. Therefore the role of secretory bodies in the stem cell treatment of autoimmune diseases is increasingly important.
Acknowledgements to Reviewers
Human Adipose-derived Stem Cells Upregulate IGF-1 and Alleviate Osteoarthritis in a Two-stage Rabbit Osteoarthritis Model
Objective: In recent times it has been recognized that mesenchymal stem cells (MSCs) possess the capability to address osteoarthritis (OA). The objective of this research was to examine the impact of injecting human adipose-derived stem cells (hADSCs) into a novel rabbit osteoarthritis model with dual damage. Methods: The OA model was established surgically first by medial collateral ligament and anterior cruciate ligament transection and medial meniscectomy then by articular cartilage full-thickness defect. Enhanced Green Fluorescence Protein expressing lentivirus FG12 was used to label hADSCs which were then injected into the knee joints. Every single rabbit was sacrificed after 4 and 8 weeks following the surgical procedure. Macroscopic examination immunohistochemistry staining magnetic resonance imaging qRT-PCR and ELISA analysis were utilized for the assessments. Results: After 4 and 8 weeks the injection of hADSCs resulted in reduced cartilage loss minimal fissures and cracks and a decrease in the volume of joint effusion and cartilage defect as measured by MRI. Moreover the application of ELISA and qRT-PCR techniques revealed that the administration of hADSCs resulted in an elevation in the IGF-1 concentration. Conclusions: Based on our findings it can be inferred that the transplantation of hADSCs facilitates the healing of articular cartilage in the osteoarthritis model of rabbits with double damage. The upregulated IGF-1 may play a crucial part in the process of cartilage repair using hADSCs. The use of hADSC transplantation could potentially be appropriate for clinical implementation in managing osteoarthritis.
Bone Marrow Mesenchymal Stem Cell-derived Exosomal microRNA-99b-5p Promotes Cell Growth of High Glucose-treated Human Umbilical Vein Endothelial Cells by Modulating THAP Domain Containing 2 Expression
Introduction: Bone marrow mesenchymal stem cell-derived exosomes (BMSC-exos) may function as novel candidates for treating diabetic wounds due to their ability to promote angiogenesis. Materials and Methods: This study investigated the effects of BMSC-exos on the growth and metastasis of human umbilical vein endothelial cells (HUVECs) treated with high glucose (HG). The exosomes were separated from BMSCs and identified. The cell phenotype was detected by 3-(45- dimethylthiazol-2-yl)-25-diphenyl tetrazolium bromide and 5-ethynyl-2’-deoxyuridine wound healing and transwell assays while the number of tubes was measured via tube formation assay. Result: The RNA and protein expression levels were studied using reverse transcription-quantitative polymerase chain reaction and western blotting whereas integration of microRNA-99b-5p (miR-99b-5p) with THAP domain containing 2 (THAP2) was confirmed via dual-luciferase reporter and RNA pull-down assays. Results of transmission electron microscopy nanoparticle tracking analysis and laser scanning confocal microscopy revealed that exosomes were successfully separated from BMSCs and endocytosed into the cytoplasm by HUVECs. Similarly BMSC-exos were found to promote the growth of HG-treated HUVECs while their growth was inhibited by suppressing miR-99b-5p. THAP2 was found to bind to miR-99b-5p where THAP2 inhibition reversed the miR-99b-5p-induced effects on cell growth migration and tube numbers. Conclusion: In conclusion miR-99b-5p in BMSC-exo protects HUVECs by negatively regulating THAP2 expression.
Distinctive Expression of MetastamiRs in Breast Cancer Mesenchymal Stem Cells Isolated from Solid Tumor
Background: MSCs are a part of the tumor microenvironment which secrete cytokines and chemokines. They can affect metastasis and the growth of tumors. metastamiRs are newly recognized regulatory elements of the metastasis pathway which are involved in epithelial-to-mesenchymal transition (EMT). Objective: In the present study we aimed to assess the expression profile of metastamiRs in the context of MSCs in correlation with their invasion and migration power. Methods: Tumor-isolated BC-MSCs and normal human mammary epithelial cells (HMECs) along with MCF-7 MDA-MB231 and MCF-10A cells were prepared and confirmed for their identity. The cells were assessed for CD44+CD24¯ percentage Oct-4 and Survivin expression. GEO KEGG and TCGA databases were investigated to detect differential miR-expressions. Real- time PCR for 13 miRs was performed using LNA primers. Ultimately Transwell-Matrigel assays as used to assess the level of migration and invasion. Results: Our results indicated that some oncomiRs like miR-10b were upregulated in BC-MSCs while the levels of miR-373 and miR-520c were similar to the MCF-10A. Generally miR-200 family members were on lower levels compared to the other miR-suppressor (miR-146a 146b and 335). miR-31 and 193b were up-regulated in MCF-10A. The most invasiveness was observed in the MDA-MB231 cell line. Conclusion: We have demonstrated that the miR-expression levels of BC-MSCs are somewhat in between MCF-7 and MDA-MB231 miR-expression levels. This could be the logic behind the moderate level of invasion in BC-MSCs. Therefore miR-therapy approaches such as miR-mimic or antagomiRs could be used for BC-MSCs in clinical cancer therapy.
Bioinformatics-based Study on the Effects of Umbilical Cord Mesenchymal Stem Cells on the Aging Retina
Background: Retinal aging is one of the common public health problems caused by population aging and has become an important cause of acquired vision loss in adults. The aim of this study was to determine the role of human umbilical cord mesenchymal stem cells (hUCMSCs) in delaying retinal ganglion cell (RGC) aging and part of the network of molecular mechanisms involved. Methods: A retinal ganglion cell senescence model was established in vitro and treated with UCMSC. Successful establishment of the senescence system was demonstrated using β- galactosidase staining. The ameliorative effect of MSC on senescence was demonstrated using CCK8 cell viability and Annexin V-PI apoptosis staining. The relevant targets of RGC MSC and senescence were mainly obtained by searching the GeneCards database. The protein interaction network among the relevant targets was constructed using the String database and Cytoscape and 10 key target genes were calculated based on the MCC algorithm based on which Gene ontologies (GO) enrichment and the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment were performed. Changes in relevant target genes were detected using real-time fluorescence quantitative PCR and the mechanism of action of UCMSC was determined by RNA interference. Results: β-galactosidase staining showed that UCMSC significantly reduced the positive results of RGC. The retinal aging process was alleviated. The bioinformatics screen yielded 201 shared genes. 10 key genes were selected by the MCC algorithm including vascular endothelial growth factor A (VEGFA) glyceraldehyde-3-phosphate dehydrogenase (GAPDH) albumin (ALB) interleukin- 6 (IL6) tumor necrosis factor (TNF) tumor protein P53 (TP53) insulin (INS) matrix metalloproteinase 9 (MMP9) epidermal growth factor (EGF) interleukin-1β (IL1B) and enrichment to related transferase activity and kinase activity regulated biological processes involved in oxidative stress and inflammation related pathways. In addition PCR results showed that all the above molecules were altered in expression after UCMSC involvement. Conclusion: This experiment demonstrated the role of UCMSC in delaying retinal ganglion cell senescence and further elucidated that UCMSC may be associated with the activation of VEGFA TP53 ALB GAPDH IL6 IL1B MMP9 genes and the inhibition of INS EGF and TNF in delaying retinal senescence.
Fucoxanthin Enhances the Antifibrotic Potential of Placenta-derived Mesenchymal Stem Cells in a CCl4-induced Mouse Model of Liver
Background: The effectiveness of fucoxanthin (Fx) in liver diseases has been reported due to its anti-inflammatory and antifibrotic effects. Mesenchymal stem cells (MSCs)-based therapy has also been proposed as a promising strategy for liver fibrosis treatment. Recent studies have shown that the co-administration of MSCs and drugs demonstrates a pronounced effect on liver fibrosis. Aim: This study aimed to determine the therapeutic potential of placenta-derived MSCs (PD-MSCs) in combination with Fx to treat liver fibrosis and evaluate their impact on the main links of liver fibrosis pathogenesis. Methods: After PD-MSCs isolation and identification outbred ICR/CD1 mice were divided into five groups: Control group CCl4group (CCl4) Fx group (CCl4+Fx) PD-MSCs group (CCl4+MSCs) and cotreatment group (CCl4+MSCs+Fx). Biochemical histopathological investigations were performed. Semiquantitative analysis of the alpha-smooth muscle actin (α-SMA+) matrix metalloproteinases (MMP-9+ MMP-13+) tissue inhibitor of matrix metalloproteinases-1 (TIMP-1+) areas and the number of positive cells in them were studied by immunohistochemical staining. Transforming growth factor-beta (TGF-β) hepatic growth factor (HGF) procollagen-1 (COL1α1) in liver homogenate and proinflammatory cytokines in blood serum were determined using an enzyme immunoassay. Results: Compared to the single treatment with PD-MSCs or Fx their combined administration significantly reduced liver enzyme activity the severity of liver fibrosis the proinflammatory cytokine levels TGF-β level α-SMA+ TIMP-1+ areas and the number of positive cells in them and increased HGF level MMP-13+ and MMP-9+ areas. Conclusion: Fx enhanced the therapeutic potential of PD-MSCs in CCl4-induced liver fibrosis but more investigations are necessary to understand the mutual impact of PD-MSCs and Fx.
In Vitro and in-silico Anti-diabetic Evaluation of the Combination of Annona squamosa Linn., Leaf Extract and Oleanolic Acid
Diabetes mellitus (DM) is a metabolic disorder caused by insufficient insulin production from pancreatic β-cells or insulin resistance; its prevalence rapidly increases worldwide. Increasing reports indicate that most plant bioactive agents exhibited alternative and safe effects in managing DM.
The study aims to evaluate the in vitro antioxidant and anti-diabetic efficacy of the combination of Annona squamosa Linn. (AS) leaf extract and Oleanolic acid (OA) using in vitro and in-silico approaches.
The leaf of AS was extracted by soxhlet extraction using n-hexane and methanol. The methanol extract of AS (MEAS) was subjected to GC-MS analysis. Quantification of total phenolic and flavonoid content and OA were carried out by HPLC and HPTLC analysis respectively. In vitro antioxidant (DPPH NO and H2O2) and anti-diabetic (α-amylase and α-glucosidase) potentials of MEAS OA and a combination of MEAS and OA (MEAS + OA) were studied at different concentrations using ascorbic acid and acarbose as standard respectively. An in-silico study determined their binding interactions with α-amylase (PDB ID-1B2Y) and α-glucosidase (PDB ID-3W37).
GC-MS analysis of MEAS revealed three major bioactives like bicyclo[7.2.0]undec-4-ene 41111-trimethyl-8-methylene-[1R-(1R*4Z9S*)]- germacrene D and undecane. The highest amount of phenolic (tannic acid and gallic acid) (150 μg/ml) and flavonoid (rutin and quercetin) (40 μg/ml) compounds were found in MEAS. OA was quantified as 356.74 ng/ml in MEAS by HPTLC. The significant inhibitory effects of MEAS OA and (MEAS + OA) on free radicals and α-amylase and α-glucosidase were observed concentration-dependent. However MEAS + OA exhibited a greater percentage of inhibition than MEAS and OA alone. The in-silico analysis revealed highest docking-score of OA (-9.8 & -8.8) Germacrene D (-7.5 & -6.5) and Bicyclo[7.2.0]undec-4-ene 41111-trimethyl-8-methylene-[1R-(1R*4Z9S*)]- (-7.0 & -6.4) against IB2Y and 3W37 proteins respectively.
We found that the combination of MEAS + OA exhibited the highest in vitro antioxidant and anti-diabetic activities compared to MEAS and OA. It concluded that OA has a significant role in potentiating the anti-diabetic effect of A. squamosa.
Environment-friendly Simple, and Straight forward Approach Towards the C-4 functionalization of (2S)-5-oxoproline Methyl Ester
4-Substituted- 5-oxo-prolinates (pyroglutamates) are important components in various natural products e.g. (-)-bulgecinine (-)-anatoxin salinosporamide as well as ACE inhibitors.
These also act as important intermediates in the synthesis of many of the bioactive molecules. Due to these reasons the synthesis of 4-substituted-(2S)-5-oxo-prolinates has received much attention over the globe in the last three decades. However most of the synthetic strategies available in the literature describe either the use of expensive lithium enolate-derived low-temperature chemistry or the rigorous reaction conditions and therefore a simple environment-friendly and cost-effective approach was truly demanding.
In our ongoing research program we required different 4-substituted pyroglutamates as intermediates and with that very basic objective we were looking for an alternate strategy which should be simple requiring cheap reagents and consequently in the process it was thought to attempt proline catalyzed aldol/alkylation reactions on pyroglutamates and the idea provided excellent outcome.
Herein we wish to report the L-proline catalyzed asymmetric functionalization at C-4 of (2S)-5-oxoproline methyl ester which furnished desired products at room temperature at the same time not requiring expensive reagents and therefore in turn cost-effective.
This new strategy explored for synthesizing 4-substituted pyroglutamates could be useful for researchers across the globe working in the area and requiring substitution at C-4 of pyroglutamates for synthesizing bioactive molecules/natural products.
A Convenient and Practical Synthesis of Novel Pyrimidine Derivatives and its Therapeutic Potential
A new series of 2-(2-(substituted aldehyde)hydrazinyl)-4-(2-chlorophenyl)-1-methyl-6-oxo-16-dihydropyrimidine-5-carbonitrile analogs (1–19) was prepared by using the Biginelli reaction.
TLC was employed to ensure the progress and confirmation of the reactions. Silica gel G was employed as the stationary phase and mobile phases such as chloroform: toluene and acetone: n-hexane were used for the synthesized compounds. NMR.MS IR CHN spectral techniques used for the characterization of synthesized compound.
The prepared derivatives were evaluated in vitro for antimicrobial activity against various bacteria and fungi using the tube dilution technique. Notably compounds 2-(2-(3-Ethoxy-4-hydroxybenzylidene)hydrazinyl)-4-(2-chlorophenyl)-1-methyl-6-oxo-16-dihydropyrimidine-5-carbonitrile T1 2-(2-(2-Hydroxybenzylidene)hydrazinyl)-4-(2-chlorophenyl)-1-methyl-6-oxo-16-dihydropyrimidine-5 carbonitrile T6 and 2-(2-(4-Hydroxybenzylidene)hydrazinyl)-4-(2-chlorophenyl)-1-methyl-6-oxo-16-dihydropyrimidine-5-carbonitrile T16 displayed significant antibacterial activity surpassing the standard drug Ampicillin. In the antifungal category compounds 2-(2-(3-Ethoxy-4-hydroxybenzylidene)hydrazinyl)-4-(2-chlorophenyl)-1-methyl-6-oxo-16-dihydropyri midine-5-carbonitrile T1 2-(2-(34-Dimethoxybenzylidene)hydrazinyl)-4-(2-chlorophenyl)-1-methyl-6-oxo-16-dihydropyrimidine-5-carbonitrile T2 and 2-(2-(24-Dichlorobenzylidene)hydrazinyl)-4-(2-chlorophenyl)-1-methyl-6-oxo-16-dihydropyrimidine-5-carbonitrile T13 were very much effective against both fungal strains A. niger as well as C. albicans. Furthermore compounds 2-(2-(2-Hydroxybenzylidene)hydrazinyl)-4-(2-chlorophenyl)-1-methyl-6-oxo-16-dihydropyrimidine-5 carbonitrile T6 2-(2-(2-Nitrobenzylidene)hydrazinyl)-4-(2-chlorophenyl)-1-methyl-6-oxo-16-dihydropyri midine-5-carbonitrile T8 2-(2-(4-Chlorobenzylidene)hydrazinyl)-4-(2-chlorophenyl)-1-methyl-6-oxo-16-dihydropyrimidine-5-carbonitrile T12 and 2-(2-(4-Dimethylaminobenzylidene)hydrazinyl)-4-(2-chlorophenyl)-1-methyl-6-oxo-16-dihydropyrimidine-5-carbonitrile T14 demonstrated remarkable antioxidant properties because of their low IC50 values in the DPPH assay. In the realm of anticancer activity 2-(2-(substituted aldehyde)hydrazinyl)-4-(2-chlorophenyl)-1-methyl-6-oxo-16-dihydro pyrimidine-5-carbonitrile T9 outperformed the standard drug Adriamycin in terms of its effectiveness against human lung cancer cells (A-549) with a GI50 value of less than 10 according to the SRB assay. In addition the antidiabetic assessment highlighted the excellent performance of compounds 2-(2-(2-Nitrobenzylidene)hydrazinyl)-4-(2-chlorophenyl)-1-methyl-6-oxo-16-dihydropyrimidine-5-carbonitrile T8 2-(2-(4-Chlorobenzylidene)hydrazinyl)-4-(2-chlorophenyl)-1-methyl-6-oxo-16-dihydropyrimidine-5-carbonitrile T12 and 2-(2-(3-Nitrobenzylidene)hydrazinyl)-4-(2-chloro phenyl)-1-methyl-6-oxo-16-dihydropyrimidine-5-carbonitrile T15 with low IC50 values when tested for their inhibition of α-amylase enzyme activity.
The synthesized derivatives demonstrated strong antimicrobial antioxidant anticancer and antidiabetic properties when assessed using specific methods and compared to established drugs. Notably compounds 2-(2-(3-Ethoxy-4-hydroxybenzylidene)hydrazinyl)-4-(2-chloro phenyl)-1-methyl-6-oxo-16-dihydropyrimidine-5-carbonitrile T1 2-(2-(2-Hydroxybenzylidene) hydrazinyl)-4-(2-chlorophenyl)-1-methyl-6-oxo-16-dihydropyrimidine-5 carbonitrile T6 and 2-(2-(24-Dichlorobenzylidene)hydrazinyl)-4-(2-chlorophenyl)-1-methyl-6-oxo-16-dihydropyrimidine -5-carbonitrile T13 2-(2-(4-Chlorobenzylidene)hydrazinyl)-4-(2-chlorophenyl)-1-methyl-6-oxo-16-dihydropyrimidine-5-carbonitrile T12 and 2-(2-(substituted aldehyde)hydrazinyl)-4-(2-chloro phenyl)-1-methyl-6-oxo-16-dihydropyrimidine-5-carbonitrile T9 exhibited even higher activity levels than the standard medications. The presence of electron-releasing groups in the synthesized compounds enhanced their antibacterial and antioxidant effects particularly against B. subtilis. On the other hand electron-withdrawing groups improved their anticancer and antidiabetic properties.
Antibacterial Potential of Tetrahydrocarbazoles (THCZ): A Review
Antibiotic resistance has become a major public threat across the globe associated with human health. Some bacterial and fungal infections produce resistance such as methicillin-resistant Staphylococcus aureus (MRSA) vancomycin-resistant Enterococcus faecium (VRE) and multidrug-resistant (MDR) species Acinetobacter baumannii etc. Tetrahydrocarbazoles (THCz) are a sub-class of indole alkaloids profoundly present in natural products and biologically active compounds and have displayed potential biological activities in literature. THCz exhibit potential antibacterial activities through major bacterial pathways like cell wall synthesis inhibition and DNA gyrase enzyme inhibition with DNA sliding clamp inhibitors and MreB inhibitors. These THCZ also showed significant in vitro antibacterial activities against bacterial-resistant species such as MRSA VRE and Acinetobacter baumannii (MDR) in literature. MTDL (Multi Target Direct ligand) approach has been significantly used for the design of THC motif-based antibacterial agents. In this review article we collected literature on THCz as a potential antibacterial agent from 2014 to date. The review study of THC core-based derivatives found excellent in vitro antibacterial profiles and revealed that they can play a significant role in drug discovery and the development of new antibiotics against various infectious diseases.
Recent Progress in Isolating and Purifying Amide Alkaloids from their Natural Habitats: A Review
Alkaloids are nitrogen-containing chemical compounds found in nature. Many alkaloids are heterocyclic in nature. They are nitrogen-based organic compounds with the nitrogen atoms enclosed in a heterocyclic ring. The chemical “pro alkaloid” is derived from the alkyl amines in it. Many ancient people long before the advent of organic chemistry recognized that many of these substances have measurable effects on the body's physiological functions. Alkaloids are a type of natural substances that are classified as secondary metabolites. Many different types of organisms create alkaloids which are a class of natural products. Alkaloids showed antifungal local anesthetic anti-inflammatory anticancer analgesic neuropharmacologic antimicrobial and many other activities. Amines as opposed to alkaloids are the more common classification for naturally occurring compounds that contain nitrogen in the exocyclic position (such as mescaline serotonin and dopamine). An amide molecule has a nitrogen atom that is chemically bound to a carbon atom in the carbonyl group. The -oic acid ending of the corresponding carboxylic acid is converted to -amide to form the correct nomenclature for an amide. This article offers an overview of numerous techniques for extracting separating and purifying alkaloids for use in natural medicine.
In-vitro Interactions between Fluconazole and Diphenyl Diselenide against Various Candida Species
In the immunocompromised population Candida species are the most aetiologic agents causing severe nosocomial fungal infections. Candida species irrespective of being commensals in the human microbiome are the fourth most prevalent source of potentially fatal yeast infections. Monotherapy is frequently employed to treat invasive fungal infections but sometimes patients do not favor the monotherapy treatment regime. It may be because of the reduced susceptibility of the pathogen toward traditional antimycotic drugs. Antimycotic drug combination therapy could be a better choice in such specific circumstances. In our study we evaluated the interactions of fluconazole with diphenyl diselenide.
The antimycotic susceptibilities of Candida species for fluconazole and diphenyl diselenide were determined by broth microdilution assay and the in-vitro interactions of fluconazole with diphenyl diselenide were studied by using disc diffusion assay and chequerboard assay. The nature of the interactions was assessed by calculating the fractional inhibitory concentration index (FICI). The interactions were also analyzed by the response surface approach.
The minimum inhibitory concentrations (MICs) for fluconazole and diphenyl diselenide as determined by the broth microdilution assay against Candida species were 4 μg/ml-512 μg/ml and 1 μg/ml-32 μg/ml respectively. The FICI values varied from 0.375 to 2.
Our finding demonstrated that there is no antagonism interaction between fluconazole and diphenyl diselenide in Candida species. Thus this innovative combination should be explored in the future.
Endophytes: Untapped Source of Antifungal Agents
Screening for novel bioactive compounds has become more critical since drug-resistant fungal infections have emerged and ethno-medicinal plants have been embarked as antifungal agents. The emphasis on medicinal plants has recently switched to the study of endophytes and their interactions with the host plant and screening of their antifungal activity. Endophytes are an endosymbiotic group of microorganisms that thrive within plant tissues without causing any symptoms or marking their presence. Endophytes have been looked into as potential resources for producing distinctive bioactive substances. The quest for bioactive natural compounds of endophytes isolated from higher plants is receiving a lot of interest from researchers worldwide as seen by the recent surge in studies and publications on antifungal potential. This review aims to comprehend the role and applications of endophytes as a promising source of antifungal agents and enlighten on their most common mode of action.
Role of Rosmarinus officinalis Aqueous Extract in Relieving the Complications Associated with Ethylene Glycol-induced Urolithiasis in Male Rats
Rosmarinus officinalis is considered one of the famous plants from ancient times for its therapeutic ability in many diseases such as headache spasms brain disorders and some pathological conditions associated with toxicity cases in the liver and kidneys.
The current research has aimed for the first time to evaluate anti-urolithiatic effect of Rosmarinus officinalis aqueous extract (RMAE) on calcium oxalate stones formation in male rats and its possible therapeutic mechanisms of action. Evaluation of total phenolic and flavonoid contents in the extract was also performed.
A calcium oxalate nephrolithiasis case was established in rats by adding ethylene glycol (1%) to the rats' daily drinking water for a duration of one month. Treatment was achieved by oral co-administration of RMAE to rats administrated ethylene glycol.
Phytochemical results showed that LC/MS-MS analysis led to the identification of 37 compounds in the phytoconstituent profile of RMAE. The biochemical results revealed significant improvement in serum kidney functions (urea creatinine and uric acid) in addition to restoring the calcium x phosphorous product and parathyroid hormone (PTH) levels in the plant-treated group compared to the non-treated one. The data have been supported by the significant decrease in lactate dehydrogenase enzyme (LDH) expression in the liver tissues reflecting the decrease in oxalate synthesis in the liver compared to the non-treated group. Kidneys' histological examinations showed the absence of oxalate crystals in the treated group and the immunohistochemical findings of osteopontin (OPN) protein revealed the impact of RMAE on OPN expression in kidney tissues. Improvements in the femur bone fractures and the parathyroid gland in the treated group were also noticed during microscopic examinations.
The anti-lithiatic effect of the extract was attributed to its influence on serum phosphate serum PTH and OPN levels in kidney tissues and decreasing synthesis of LDH in liver tissues in addition to the prevention of secondary disease incidences such as secondary hyperparathyroidism and cardiovascular diseases. On the other hand the plant's considerable content of phenolics and flavonoids has been found to play a role in controlling kidney stone progression episodes.