scholarly journals Blocking of inflammatory heparan sulfate domains by specific antibodies is not protective in experimental glomerulonephritis

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0261722
Author(s):  
Jasper J. van Gemst ◽  
Nathalie J. H. G. Passmann ◽  
Angelique L. W. M. M. Rops ◽  
Toin H. van Kuppevelt ◽  
Jo H. Berden ◽  
...  
Keyword(s):  
Renal Function ◽  
Heparan Sulfate ◽  
Therapeutic Potential ◽  
Inflammatory Cells ◽  
Renal Outcome ◽  
Future Research ◽  
Transient Effects ◽  
Fibrin Deposition ◽  
Single Chain ◽  
Experimental Glomerulonephritis

Glomerulonephritis is an acquired serious glomerular disease, which involves the interplay of many factors such as cytokines, chemokines, inflammatory cells, and heparan sulfate (HS). We previously showed that blocking of inflammatory heparan sulfate domains on cultured glomerular endothelium by specific anti-HS single chain antibodies reduced polymorphonuclear cell (PMN) adhesion and chemokine binding. We hypothesized that injection of anti-HS antibodies in PMN-driven experimental glomerulonephritis should reduce glomerular influx of PMNs and thereby lead to a better renal outcome. In contrast to our hypothesis, co-injection of anti-HS antibodies did not alter the final outcome of anti-glomerular basement membrane (anti-GBM)-induced glomerulonephritis. Glomerular PMN influx, normally peaking 2 hours after induction of glomerulonephritis with anti-GBM IgG was not reduced by co-injection of anti-HS antibodies. Four days after induction of glomerulonephritis, albuminuria, renal function, glomerular hyalinosis and fibrin deposition were similar in mice treated and not treated with anti-HS antibodies. Interestingly, we observed transient effects in mice co-injected with anti-HS antibodies compared to mice that did not receive anti-HS antibodies: (i) a decreased renal function 2 hours and 1 day after induction of glomerulonephritis; (ii) an increased albuminuria after 2 hours and 1 day; (iii) an increased glomerular fibrin deposition after 1 day; (iv) a reduced glomerular macrophage influx after 1 day; (v) a sustained glomerular presence of PMNs at day 1 and 4, accompanied by an increased renal expression of IL-6, CXCL1, ICAM-1, L-selectin, CD11b and NF-κB. The mechanism underlying these observations induced by anti-HS antibodies remains unclear, but may be explained by a temporarily altered glycocalyx and/or altered function of PMNs due to the binding of anti-HS antibodies. Nevertheless, the evaluated anti-HS antibodies do not show therapeutic potential in anti-GBM-induced glomerulonephritis. Future research should evaluate other strategies to target HS domains involved in inflammatory processes during glomerulonephritis.

Phytochemical, Pharmacological Activities and Ayurvedic Significances of Magical Plant Mimosa pudica Linn

2020 ◽  
Vol 17 ◽  
Author(s):  
Vijay Kumar
Keyword(s):  
Therapeutic Potential ◽  
Wide Spectrum ◽  
Chemical Constituents ◽  
Future Research ◽  
Mimosa Pudica ◽  
Pharmacological Activities ◽  
Medicinal Uses ◽  
Traditional Medicines ◽  
Crude Extracts ◽  
Anti Cancer

: Mimosa pudica Linn is an integrated part of Traditional Medicines Systems of India, China, Africa, Korea and America. It has been used from centuries in traditional medicines to cure different diseases like fever, diabetes, constipation, jaundice, ulcers, biliousness, and dyspepsia. It is an important ingredient of wide class of herbal formulations. To assess the scientific evidence for therapeutic potential of Mimosa pudica Linn and to identify the gaps for future research. The available information on the ethno-medicinal uses, phytochemistry, pharmacology and toxicology of Mimosa pudica Linn was collected via a library and electronic searches in Sci-Finder, Pub-Med, Science Direct, Google Scholar for the period, 1990 to 2020. In traditional medicinal systems, variety of ethno-medicinal applications of Mimosa pudica Linn has been noticed. Phytochemical investigation has resulted in identification of 40 well known chemical constituents, among which alkaloids, phenols and flavionoids are the predominant groups. The crude extracts and isolates have exhibited a wide spectrum of in vitro and in vivo pharmacological activities including anti-cancer, anti-inflammation, osteoporosis, neurological disorders, hypertension etc.. To quantify the Mimosa pudica Linn and its formulations, analytical techniques like HPLC and HPTLC has shown dominancy with good range of recovery and detection limit. Mimosa pudica Linn is the well-known herb since an ancient time. The pharmacological results supported some of the applications of Mimosa pudica Linn in traditional medicine systems. Perhaps, the predominance of alkaloids, phenols and flavionoids are responsible for the pharmacological activities the crude extracts and isolates of Mimosa pudica Linn. Further, there is need to isolate and evaluate the active chemical constituents of Mimosa pudica Linn having significant medicinal values. In future, it is important to study the exact mechanism associated with the phytochemicals of Mimosa pudica Linn especially on anti-cancer activities. Notably, toxicity studies on Mimosa pudica Linn are limited which are to be explored in future for the safe application of Mimosa pudica Linn and its formulations.

scholarly journals Efficacy of Phytocannabinoids in Epilepsy Treatment: Novel Approaches and Recent Advances

2021 ◽  
Vol 18 (8) ◽  
pp. 3993
Author(s):  
Aaron M. Farrelly ◽  
Styliani Vlachou ◽  
Konstantinos Grintzalis
Keyword(s):  
Therapeutic Potential ◽  
Significant Proportion ◽  
Future Research ◽  
Specific Reference ◽  
Undesirable Side Effect ◽  
Treatment Resistant ◽  
Current Review ◽  
Epilepsy Treatment ◽  
Clinical Environments

Epilepsy is a neurological disorder mainly characterised by recurrent seizures that affect the entire population diagnosed with the condition. Currently, there is no cure for the disease and a significant proportion of patients have been deemed to have treatment-resistant epilepsy (TRE). A patient is deemed to have TRE if two or more antiepileptic drugs (AEDs) fail to bring about seizure remission. This inefficacy of traditional AEDs, coupled with their undesirable side effect profile, has led to researchers considering alternative forms of treatment. Phytocannabinoids have long served as therapeutics with delta-9-THC (Δ9-THC) receiving extensive focus to determine its therapeutic potential. This focus on Δ9-THC has been to the detriment of analysing the plethora of other phytocannabinoids found in the cannabis plant. The overall aim of this review is to explore other novel phytocannabinoids and their place in epilepsy treatment. The current review intends to achieve this aim via an exploration of the molecular targets underlying the anticonvulsant capabilities of cannabidiol (CBD), cannabidavarin (CBDV), delta-9-tetrahydrocannabivarin (Δ9-THCV) and cannabigerol (CBG). Further, this review will provide an exploration of current pre-clinical and clinical data as it relates to the aforementioned phytocannabinoids and the treatment of epilepsy symptoms. With specific reference to epilepsy in young adult and adolescent populations, the exploration of CBD, CBDV, Δ9-THCV and CBG in both preclinical and clinical environments can guide future research and aid in the further understanding of the role of phytocannabinoids in epilepsy treatment. Currently, much more research is warranted in this area to be conclusive.

scholarly journals Structural and Functional Remodeling of Mitochondria in Cardiac Diseases

2021 ◽  
Vol 22 (8) ◽  
pp. 4167
Author(s):  
Xiaonan Sun ◽  
Jalen Alford ◽  
Hongyu Qiu
Keyword(s):  
Regulatory Network ◽  
Molecular Basis ◽  
Therapeutic Potential ◽  
Research Direction ◽  
Future Research ◽  
Cardiac Diseases ◽  
Functional Remodeling ◽  
Underlying Mechanisms ◽  
Mitochondrial Remodeling ◽  
Normal Cellular Function

Mitochondria undergo structural and functional remodeling to meet the cell demand in response to the intracellular and extracellular stimulations, playing an essential role in maintaining normal cellular function. Merging evidence demonstrated that dysregulation of mitochondrial remodeling is a fundamental driving force of complex human diseases, highlighting its crucial pathophysiological roles and therapeutic potential. In this review, we outlined the progress of the molecular basis of mitochondrial structural and functional remodeling and their regulatory network. In particular, we summarized the latest evidence of the fundamental association of impaired mitochondrial remodeling in developing diverse cardiac diseases and the underlying mechanisms. We also explored the therapeutic potential related to mitochondrial remodeling and future research direction. This updated information would improve our knowledge of mitochondrial biology and cardiac diseases’ pathogenesis, which would inspire new potential strategies for treating these diseases by targeting mitochondria remodeling.

scholarly journals Inhibitory Effects of Breast Milk-Derived Lactobacillus rhamnosus Probio-M9 on Colitis-Associated Carcinogenesis by Restoration of the Gut Microbiota in a Mouse Model

Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1143
Author(s):  
Haiyan Xu ◽  
Keizo Hiraishi ◽  
Lin-Hai Kurahara ◽  
Yuko Nakano-Narusawa ◽  
Xiaodong Li ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Lactobacillus Rhamnosus ◽  
Tumor Model ◽  
Intestinal Bacteria ◽  
Inflammatory Cells ◽  
Shannon Index ◽  
Tumor Formation ◽  
Intestinal Bacterium ◽  
Α Diversity ◽  
Inflammatory Bowel

Chronic inflammation is a risk factor for colorectal cancer, and inflammatory cytokines secreted from inflammatory cells and active oxygen facilitate tumorigenesis. Intestinal bacteria are thought to regulate tumorigenesis. The longer the breastfeeding period, the lower is the risk of inflammatory bowel disease. Here, we investigated preventive effects of the probiotic Lactobacillus rhamnosus M9 (Probio-M9) on colitis-associated tumorigenesis. An inflammatory colorectal tumor model was established using a 6-week-old male C57BL/6NCrSlc mouse, which was intraperitoneally administered with azoxymethane (AOM: 12 mg/kg body weight). On weeks 2 and 4, 2% dextran sulfate sodium (DSS) was administered to mice for 7 days through drinking water. On weeks 8 and 10, Probio-M9 (2 × 109/day) was orally administered for 7 days. Animals were sacrificed at 20 weeks after AOM administration and immunohistochemical staining and Western blotting was performed. The α-diversity of microflora (Shannon index), principal coordinate analysis, and distribution of intestinal bacterium genera and metabolic pathways were compared. The AOM/DSS group showed weight loss, diarrhea, intestinal shortening, increased number of colon tumors, proliferating tumorigenesis, increased inflammation score, fibrosis, increased CD68+, or CD163+ macrophage cells in the subserosal layer of non-tumor areas. Inflammation and tumorigenesis ameliorated after Probio-M9 treatment. Fecal microbial functions were altered by AOM/DSS treatment. Probio-M9 significantly upregulated the fecal microbial diversity and reversed fecal microbial functions. Thus, Probio-M9 could suppress tumor formation in the large intestine by regulating the intestinal environment and ameliorating inflammation, suggesting its therapeutic potential for treatment of inflammation and colitis-associated tumorigenesis.

scholarly journals Liposomal Ellagic Acid Alleviates Cyclophosphamide-Induced Toxicity and Eliminates the Systemic Cryptococcus neoformans Infection in Leukopenic Mice

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 882
Author(s):  
Masood Alam Khan ◽  
Arif Khan ◽  
Mohd Azam ◽  
Khaled S. Allemailem ◽  
Faris Alrumaihi ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Renal Function ◽  
Survival Rate ◽  
Cryptococcus Neoformans ◽  
Ellagic Acid ◽  
Histological Analysis ◽  
Reduced Glutathione ◽  
Inflammatory Cells ◽  
Fungal Burden ◽  
Fungal Load

Cryptococcus neoformans infections rose sharply due to rapid increase in the numbers of immunocompromised individuals in recent years. Treatment of Cryptococcosis in immunocompromised persons is largely very challenging and hopeless. Hence, this study aimed to determine the activity of ellagic acid (EA) in the treatment of C. neoformans in cyclophosphamide injected leukopenic mice. A liposomal formulation of ellagic acid (Lip-EA) was prepared and characterized, and its antifungal activity was assessed in comparison to fluconazole (FLZ). The efficacy of the drug treatment was tested by assessing survival rate, fungal burden, and histological analysis in lung tissues. The safety of the drug formulations was tested by investigating hepatic, renal function, and antioxidant levels. The results of the present work demonstrated that Lip-EA, not FLZ, effectively eliminated C. neoformans infection in the leukopenic mice. Mice treated with Lip-EA (40 mg/kg) showed 70% survival rate and highly reduced fungal burden in their lung tissues, whereas the mice treated with FLZ (40 mg/kg) had 20% survival rate and greater fungal load in their lungs. Noteworthy, Lip-EA treatment alleviated cyclophosphamide-induced toxicity and restored hepatic and renal function parameters. Moreover, Lip-EA treatment restored the levels of superoxide dismutase and reduced glutathione and catalase in the lung tissues. The effect of FLZ or EA or Lip-EA against C. neoformans infection was assessed by the histological analysis of lung tissues. Lip-EA effectively reduced influx of inflammatory cells, thickening of alveolar walls, congestion, and hemorrhage. The findings of the present study suggest that Lip-EA may prove to be a promising therapeutic formulation against C. neoformans in immunocompromised persons.

scholarly journals Specific heparan sulfate modifications stabilize the synaptic organizer MADD-4/Punctin at C. elegans neuromuscular junctions

Genetics ◽  
2021 ◽  
Author(s):  
Mélissa Cizeron ◽  
Laure Granger ◽  
Hannes E BÜlow ◽  
Jean-Louis Bessereau
Keyword(s):  
Heparan Sulfate ◽  
Matrix Protein ◽  
Neuromuscular Junctions ◽  
Core Protein ◽  
Extracellular Matrix Protein ◽  
Inhibitory Synapses ◽  
Single Chain ◽  
C Elegans ◽  
Sugar Chains

Abstract Heparan sulfate proteoglycans contribute to the structural organization of various neurochemical synapses. Depending on the system, their role involves either the core protein or the glycosaminoglycan chains. These linear sugar chains are extensively modified by heparan sulfate modification enzymes, resulting in highly diverse molecules. Specific modifications of glycosaminoglycan chains may thus contribute to a sugar code involved in synapse specificity. Caenorhabditis elegans is particularly useful to address this question because of the low level of genomic redundancy of these enzymes, as opposed to mammals. Here, we systematically mutated the genes encoding heparan sulfate modification enzymes in C. elegans and analyzed their impact on excitatory and inhibitory neuromuscular junctions. Using single chain antibodies that recognize different heparan sulfate modification patterns, we show in vivo that these two heparan sulfate epitopes are carried by the SDN-1 core protein, the unique C. elegans syndecan orthologue, at neuromuscular junctions. Intriguingly, these antibodies differentially bind to excitatory and inhibitory synapses, implying unique heparan sulfate modification patterns at different neuromuscular junctions. Moreover, while most enzymes are individually dispensable for proper organization of neuromuscular junctions, we show that 3-O-sulfation of SDN-1 is required to maintain wild-type levels of the extracellular matrix protein MADD-4/Punctin, a central synaptic organizer that defines the identity of excitatory and inhibitory synaptic domains at the plasma membrane of muscle cells.

scholarly journals Heparan Sulfate Mimetics in Cancer Therapy: The Challenge to Define Structural Determinants and the Relevance of Targets for Optimal Activity

Molecules ◽  
2018 ◽  
Vol 23 (11) ◽  
pp. 2915 ◽  
Author(s):  
Cinzia Lanzi ◽  
Giuliana Cassinelli
Keyword(s):  
Heparan Sulfate ◽  
Therapeutic Potential ◽  
Anticoagulant Activity ◽  
Growth Factor Receptor ◽  
Biological Behavior ◽  
Antitumor Action ◽  
Structural Determinants ◽  
Antitumor Effects ◽  
Combination Treatments ◽  
Heparin Derivatives

Beyond anticoagulation, the therapeutic potential of heparin derivatives and heparan sulfate (HS) mimetics (functionally defined HS mimetics) in oncology is related to their ability to bind and modulate the function of a vast array of HS-binding proteins with pivotal roles in cancer growth and progression. The definition of structural/functional determinants and the introduction of chemical modifications enabled heparin derivatives to be identified with greatly reduced or absent anticoagulant activity, but conserved/enhanced anticancer activity. These studies paved the way for the disclosure of structural requirements for the inhibitory effects of HS mimetics on heparanase, selectins, and growth factor receptor signaling, as well as for the limitation of side effects. Actually, HS mimetics affect the tumor biological behavior via a multi-target mechanism of action based on their effects on tumor cells and various components of the tumor microenvironment. Emerging evidence indicates that immunomodulation can participate in the antitumor activity of these agents. Significant ability to enhance the antitumor effects of combination treatments with standard therapies was shown in several tumor models. While the first HS mimetics are undergoing early clinical evaluation, an improved understanding of the molecular contexts favoring the antitumor action in certain malignancies or subgroups is needed to fully exploit their potential.

scholarly journals Bioactive Agent-Loaded Electrospun Nanofiber Membranes for Accelerating Healing Process: A Review

Membranes ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 702
Author(s):  
Seyyed-Mojtaba Mousavi ◽  
Zohre Mousavi Nejad ◽  
Seyyed Alireza Hashemi ◽  
Marjan Salari ◽  
Ahmad Gholami ◽  
...  
Keyword(s):  
Wound Healing ◽  
Chronic Wounds ◽  
Therapeutic Potential ◽  
Healing Process ◽  
Wound Dressings ◽  
Future Research ◽  
Wound Healing Process ◽  
Nanofiber Membranes ◽  
Bioactive Agents ◽  
Bioactive Agent

Despite the advances that have been achieved in developing wound dressings to date, wound healing still remains a challenge in the healthcare system. None of the wound dressings currently used clinically can mimic all the properties of normal and healthy skin. Electrospinning has gained remarkable attention in wound healing applications because of its excellent ability to form nanostructures similar to natural extracellular matrix (ECM). Electrospun dressing accelerates the wound healing process by transferring drugs or active agents to the wound site sooner. This review provides a concise overview of the recent developments in bioactive electrospun dressings, which are effective in treating acute and chronic wounds and can successfully heal the wound. We also discuss bioactive agents used to incorporate electrospun wound dressings to improve their therapeutic potential in wound healing. In addition, here we present commercial dressings loaded with bioactive agents with a comparison between their features and capabilities. Furthermore, we discuss challenges and promises and offer suggestions for future research on bioactive agent-loaded nanofiber membranes to guide future researchers in designing more effective dressing for wound healing and skin regeneration.

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