Human spermatozoa exhibit a capacity to generate ROS and initiate peroxidation of the unsaturated fatty acids in the sperm plasma membrane, which plays a key role in the etiology of male infertility. The short half-life and limited diffusion of these molecules is consistent with their physiologic role in key biological events such as acrosome reaction and hyperactivation. The intrinsic reactivity of these metabolites in peroxidative damage induced by ROS, particularly $H_2O_2$ and the superoxide anion, has been proposed as a major cause of defective sperm function in cases of male infertility. The number of antioxidants known to attack different stages of peroxidative damage is growing, and it will be of interest to compare alpha-tocopherol and ascorbic acid with these for their therapeutic potential in vitro and in vivo. Both spermatozoa and leukocytes generate ROS, although leukocytes produce much higher levels. The clinical significance of leukocyte presence in semen is controversial. Seminal plasma confers some protection against ROS damage because it contains enzymes that scavenge ROS, such as catalase and superoxide dismutase. A variety of defense mechanisms comprising a number of antioxidants can be employed to reduce or overcome oxidative stress caused by excessive ROS. Determination of male infertility etiology is important, as it will help us develop effective therapies to overcome excessive ROS generation. ROS can have both beneficial and detrimental effects on the spermatozoa and the balancing between the amounts of ROS produced and the amounts scavenged at any moment will determine whether a given sperm function will be promoted or jeopardized. Accurate assessment of ROS levels and, subsequently, OS is Vital, as this will help clinicians both elucidate the fertility status and identify the subgroups of patients that respond or do not respond to these therapeutic strategies. The overt commercial claims of antioxidant benefits and supplements for fertility purposes must be cautiously looked into, until proper multicentered clinical trials are studied. From the current data it appears that no Single adjuvant will be able to enhance the fertilizing capacity of sperm in infertile men, and a combination of the possible strategies that are not toxic at the dosage used would be a feasible approach.
Objective: Since Ulmus davidiana Planch (Ulmaceae) has been known to have anti-inflammatory and protective effects on damaged tissue, inflammation and bone among other functions, this study was undertaken to address whether the water extract of the bark of Ulmus davidiana Planch (Ulmaceae) (UD) could modulate the expression of inducible inflammatory cytokines in mice. The present study was also done in order to assess the therapeutic effects of UD in collagen-induced arthritis (CIA) in mice. Methods : DBA/1 mice were immunized with bovine type II collagen. After a second collagen immunization, mice were treated with UD orally at 100 mg/kg once a day for 3 weeks. Paws were evaluated macroscopically for redness, swelling and deformities. The levels of $TNF-{\alpha}\;and\;IL-1{\beta}$ in the ankle were examined. The severity of arthritis within the knee joints was evaluated by histological assessment of cartilage destruction and pannus formation. Results : Administration of UD significantly suppressed the progression of CIA and inhibited the production of $TNF-{\alpha}\;and\;IL-1{\beta}$ in the paws. The erosion of cartilage was dramatically reduced in mouse knees after treatment with UD. In the serum of UD-treated mice, the levels of IL-4 and IL-10, anti-inflammatory cytokines, were increased. Conclusion : From the results, it was concluded that administration of UD has therapeutic effects on CIA including protection of cartilage and RA for a potential therapy.
Wan-Mohtar, Wan Abd Al Qadr Imad;Young, Louise;Abbott, Grainne M.;Clements, Carol;Harvey, Linda M.;McNeil, Brian
Journal of Microbiology and Biotechnology
/
v.26
no.6
/
pp.999-1010
/
2016
Ganoderma lucidum BCCM 31549 has a long established role for its therapeutic activities. In this context, much interest has focused on the possible functions of the (1,3)-β-D-glucan (G) produced by these cultures in a stirred-tank bioreactor and extracted from their underutilized mycelium. In the existing study, we report on the systematic production of G, and its sulfated derivative (GS). The aim of this study was to investigate G and its GS from G. lucidum in terms of their antibacterial properties and cytotoxicity spectrum against human prostate cells (PN2TA) and human caucasian histiocytic lymphoma cells (U937). 1H NMR for both G and GS compounds showed β-glycosidic linkages and structural similarities when compared with two standards (laminarin and fucoidan). The existence of characteristic absorptions at 1,170 and 867 cm-1 in the FTIR (Fourier Transform Infrared Spectroscopy) for GS demonstrated the successful sulfation of G. Only GS exhibited antimicrobial activity against a varied range of test bacteria of relevance to foodstuffs and human health. Moreover, both G and GS did not show any cytotoxic effects on PN2TA cells, thus helping demonstrate the safety of these polymers. Moreover, GS showed 40% antiproliferation against cancerous U937 cells at the low concentration (60 μg/ ml) applied in this study compared with G (10%). Together, this demonstrates that sulfation clearly improved the solubility and therapeutic activities of G. The water-soluble GS demonstrates the potential multifunctional effects of these materials in foodstuffs.
The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
/
v.30
no.1
/
pp.74-86
/
2017
Objectives : This study aimed to assess the scientific evidence for the use of Hwanglyeonhaedok-tang, a traditional herbal formula, in the treatment of rhinitis, and prepare the basis for the investigational new drug application by analyzing the experimental studies. Methods : Ten electronic databases were searched up to December, 2016 without language limitation. Experimental studies on the anti-inflammatory and anti-allergic effects of Hwanglyeonhaedok-tang against rhinitis were included. We extracted data about study design, characteristics of intervention, outcomes, and pharmacological effects from the included studies and summarized them. Results : Eight hundred and thirty-three potentially relevant studies were identified, of which 18 experimental studies met our inclusion criteria. Of 18 included studies, 5 had conducted cell viability test, and all studies had reported that Hwanglyeonhaedok-tang was non-cytotoxic. Hwanglyeonhaedok-tang exhibits anti-inflammatory effect by regulating the inflammation-related cytokines including nitric oxide(NO), prostaglandin $E_2(PGE_2)$, interleukin-6(IL-6), and tumor necrosis $factor-{\alpha}(TNF-{\alpha})$ in vitro and in vivo. Hwanglyeonhaedok-tang exhibits anti-allergic effect by suppressing eosinophil, and histamine levels. Hwanglyeonhaedok-tang helps in the recovery of nasal mucous membrane by supressing goblet cells, heat shock protein 70, and substance P. Conclusions : This study suggests that Hwanglyeonhaedok-tang has the potential to be developed as therapeutic agent for rhinitis. Further experimental and clinical studies needed to be performed to prove the safety and efficacy.
Kim, Seong-Il;Raffi Mikaelian;Kwak, Jin-Hwan;Kim, In-Chull;Lee, Chang-Ho
Biomolecules & Therapeutics
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v.3
no.4
/
pp.316-321
/
1995
All the pharmacological studies of LB17522 described here were carried out with high doses (fifteen to sixty times of the therapeutic dose) to determine an indication of potential side effects in clinical use in terms of the acute clinical signs, cardiovascular and central nervous system. LB10522 does not produce any observable clinical signs except for the symptoms such as moist eye, skin rash, slight salivation, vomitting, and slightly reduced activity. The effects of LB10522 on the hemodynamics and cardiac function of anesthetized beagle dogs are as follows; heart rates and mean arterial blood pressure had a tendency to increase mildly, which is a normal finding in anesthetized dogs. All the animals except for one showed relatively stable respiratory rates throughout the observation period. Each animal treated with LB10522 showed slight increase in the left cardiac work and left ventricular stroke work which are mainly related to corresponding increases in cardiac output. Femoral blood flow were shown to be increased in some animals treated with LB10522. The epileptogenic activities of various cephalosporins were assessed by a direct intracerebral injection of appropriate concentration of test articles. The CD$_{50}$ values (nmol) obtained from the analysis of the dose-response data are as follows; 78.2, 175.3, 156.3, and 53.5 for cefazolin, cephaloridine, ceftazidime, and LB 10522, respectively. LB10522 seems to be equipotent with cefazolin or to be three times more potent than cephaloridine and ceftazidime in causing adverse CNS stimulation. Taken into consideration all the information obtained, LB10522 is not supposed to induce much changes in the functions examined in these studies in man at therapeutic doses.s.
In recent years, inhibition of HDACs has emerged as a potential strategy to reverse aberrant epigenetic changes associated with cancer, and several classes of HDAC inhibitors have been found to have potent and specific anticancer activities in preclinical studies. But their precise mechanism of action has not been elucidated. In this study, a novel synthetic inhibitor of HDAC, 3-(4-dimethylamino phenyl)-N-hydroxy-2-propenamide [IN-2001] was examined for its antitumor activity and the underlying molecular mechanisms of any such activity on human breast cancer cell lines. IN-2001 effectively inhibited cellular HDAC activity ($IC_{50}$ = 0.585 nM) inMDA-MB-231 human breast cancer cells. IN-2001 caused a significant dose-dependent inhibition of cell proliferation in estrogen receptor (ER) negative MDA-MB-231human breast cancer cells. Cell cycle analysis revealed that the growth inhibitory effects of IN-2001 might be attributed to cell cycle arrest at $G_0/G_1$ and/or $G_2$/Mphase and subsequent apoptosis in human breast cancer cells. These events are accompanied by modulating several cell cycle and apoptosis regulatory genes such as CDK inhibitors $p21^{WAF1}$ and $p27^{KIP1}$ cyclin D1, and other tumor suppressor genes such as cyclin D2. Collectively, IN-2001 inhibited cell proliferation and induced apoptosis in human breast cancer cells and these findings may provide new therapeutic approaches, combination of antiestrogen together with a HDAC inhibitor, in the hormonal therapy-resistant ER-negative breast cancers. In summary, our data suggest that this histone deacetylase inhibitor, IN-2001, is a novel promising therapeutic agent with potent antitumor effects against human breast cancers.
Hyperlipidemia, which is closely associated with a fatty diet and aging, is commonly observed in the western and aged society. Therefore, a novel therapeutic approach for this disease is critical, and an immunological view has been suggested as a novel strategy, because hyperlipidemia is closely associated with inflammation and immune dysfunction. In this study, the effects of an aqueous extract of Rubus occidentalis (RO) in obese mice were investigated using immunological indexes. The mice were fed a high-fat diet (HFD) to induce hyperlipidemia, which was confirmed by biochemical analysis and examination of the mouse physiology. Two different doses of RO and rosuvastatin, a cholesterol synthesis inhibitor used as a control, were orally administered. Disturbances in immune cellularity as well as lymphocyte proliferation and cytokine production were significantly normalized by oral administration of RO, which also decreased the elevated serum tumor necrosis factor $(TNF)-{\alpha}$ level and total cholesterol. The specific immune-related actions of RO comprised considerable improvement in cytotoxic T cell killing functions and regulation of antibody production to within the normal range. The immunological evidence confirms the significant cholesterol-lowering effect of RO, suggesting its potential as a novel therapeutic agent for hyperlipidemia and associated immune decline.
Hernandez, Rosa;Jimenez-Luna, Cristina;Perales-Adan, Jesus;Perazzoli, Gloria;Melguizo, Consolacion;Prados, Jose
Biomolecules & Therapeutics
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v.28
no.1
/
pp.34-44
/
2020
Mesenchymal stem cells (MSCs) have been proposed as an alternative therapy to be applied into several pathologies of the nervous system. These cells can be obtained from adipose tissue, umbilical cord blood and bone marrow, among other tissues, and have remarkable therapeutic properties. MSCs can be isolated with high yield, which adds to their ability to differentiate into non-mesodermal cell types including neuronal lineage both in vivo and in vitro. They are able to restore damaged neural tissue, thus being suitable for the treatment of neural injuries, and possess immunosuppressive activity, which may be useful for the treatment of neurological disorders of inflammatory etiology. Although the long-term safety of MSC-based therapies remains unclear, a large amount of both pre-clinical and clinical trials have shown functional improvements in animal models of nervous system diseases following transplantation of MSCs. In fact, there are several ongoing clinical trials evaluating the possible benefits this cell-based therapy could provide to patients with neurological damage, as well as their clinical limitations. In this review we focus on the potential of MSCs as a therapeutic tool to treat neurological disorders, summarizing the state of the art of this topic and the most recent clinical studies.
Morishita, Masayo;Mevius, Damiaan;Shen, Yunpeng;Di Luccio, Eric
Current Research on Agriculture and Life Sciences
/
v.31
no.3
/
pp.157-164
/
2013
Chromatin remodelers that include histone methyl transferases (HMTases) are becoming a focal point in cancer drug development. The NSD family of three HMTases, NSD1, NSD2/MMSET/WHSC1, and NSD3/WHSC1L are bona fide oncogenes found aberrantly expressed in several cancers, suggesting their potential role for novel therapeutic strategies. Several histone modifiers including HMTase have clear roles in human carcinogenesis but the extent of their functions and regulations are not well understood, especially in pathological conditions. The extents of the NSDs biological roles in normal and pathological conditions remain unclear. In particular, the substrate specificity of the NSDs remains unsettled and discrepant data has been reported. NSD2/MMSET is a focal point for therapeutic interventions against multiple myeloma and especially for t(4;14) myeloma, which is associated with a significantly worse prognosis than other biological subgroups. Multiple myeloma is the second most common hematological malignancy in the United States, after non-Hodgkin lymphoma. Herein, as a first step before entering a pipeline for protein x-ray crystallography, we cloned, recombinantly expressed and purified the catalytic SET domain of NSD2. Next, we demonstrated the catalytic activities, in vitro, of the recombinantly expressed NSD2-SET on H3K36 and H4K20, its biological targets at the chromatin.
Lim, Yun-Sook;Nguyen, Lap P.;Lee, Gun-Hee;Lee, Sung-Geun;Lyoo, Kwang-Soo;Kim, Bumseok;Hwang, Soon B.
Molecules and Cells
/
v.44
no.9
/
pp.688-695
/
2021
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has become a global health concern. Various SARS-CoV-2 vaccines have been developed and are being used for vaccination worldwide. However, no therapeutic agents against coronavirus disease 2019 (COVID-19) have been developed so far; therefore, new therapeutic agents are urgently needed. In the present study, we evaluated several hepatitis C virus direct-acting antivirals as potential candidates for drug repurposing against COVID-19. Theses include asunaprevir (a protease inhibitor), daclatasvir (an NS5A inhibitor), and sofosbuvir (an RNA polymerase inhibitor). We found that asunaprevir, but not sofosbuvir and daclatasvir, markedly inhibited SARS-CoV-2-induced cytopathic effects in Vero E6 cells. Both RNA and protein levels of SARS-CoV-2 were significantly decreased by treatment with asunaprevir. Moreover, asunaprevir profoundly decreased virion release from SARS-CoV-2-infected cells. A pseudoparticle entry assay revealed that asunaprevir blocked SARS-CoV-2 infection at the binding step of the viral life cycle. Furthermore, asunaprevir inhibited SARS-CoV-2 propagation in human lung Calu-3 cells. Collectively, we found that asunaprevir displays broad-spectrum antiviral activity and therefore might be worth developing as a new drug repurposing candidate for COVID-19.
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