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Jun 2017 DOI 10.14302/issn.2474-7785.jarh-17-1578
Frailty describes a medical syndrome that confers increased vulnerability to disproportionate changes in health status following minor stressors. With loss of homeostatic reserve in multiple physiological systems, frailty conveys an increased risk of adverse health outcomes. Despite the lack of a clear universal definition, the utilisation of two landmark operational models has allowed a rapid expansion in frailty-centred research. The pathophysiology of frailty is yet to be elucidated in the literature, but a critical role for a heightened inflammatory state is hypothesised. Raised levels of pro-inflammatory cytokines are associated with frailty, with emerging evidence relating their biochemical action with development of the frailty phenotype. Dysregulation of both the innate and adaptive immune system are key components of the frailty syndrome. Remodelling of the T cell compartment and upregulated inflammatory pathways are theorised to propagate the heightened inflammatory state critical in the frailty syndrome. Increased neutrophil counts, in conjunction with ineffective neutrophil migration associated with age, is theorised to produce tissue damage and secondary inflammation conducive of the inflammatory picture in frailty. Beyond the gold standard of the comprehensive geriatric assessment, management of frailty is a fast-evolving area of research. Exercise interventions have shown promising results, improving functional ability and showing beneficial immunomodulation. Vitamin D supplementation, with proposed anti-inflammatory effects, nutritional support and pharmacological treatments all provide promising areas for future therapeutic intervention.
Mar 2025 DOI 10.14302/issn.2693-1176.ijgh-25-5429
Malaria and bacteraemia are significant public health concerns and economic threats. In Africa, the intensity for simultaneous transmission and co-infection of Plasmodium spp and other bacteria pathogens are extremely high. It is believed that malaria suppress the immune system and enable the translocation of bacteria in the gastrointestinal tract to other cellular compartments in the body. Some of the factors that contributed to the co-emergence of these pathogens are poor access to clean water, sanitation and hygiene (WASH), poor infection control measures, inefficient health care systems. In addition, the similarities in the clinical signs and symptoms of these febrile diseases and the fact that the etiologic diagnostic testing can be complex, costly, and limited are the reasons why clinicians in resource-constrained setting often prescribe antibiotics empirically prior to or without laboratory testing to prevent severe outcomes in any patient hospitalized with malaria. However, this indiscriminate use of antibiotics has been identified as the driving force for antibiotic resistance, which is already at alarming rate in malaria endemic nations. In developed countries where malaria had been previously eradicated, there are increasing reports of imported malaria with concurrent bacteraemia. In this review, we emphasized the role of malaria in the indiscriminate use of antibiotics and the fact that eliminating malaria in Africa is one of the best strategies to address the emergence and the global spread of multi-drug resistance organisms.
Jun 2024 DOI 10.14302/issn.2374-9431.jbd-24-5077
Dengue is a global arbovirus disease primarily carried by Aedes aegypti and Aedes albopictus mosquitoes. It has four serotypes (DENV1, DENV2, DENV3, and DENV4) and is classified into distinct genotypes. The epidemic is complicated by immunological interactions and viral lineage turnover. Neurological problems are commonly associated with DENV2 and DENV3, with DENV2 displaying the most severe symptoms. Direct viral invasion, host-mediated immune system reactions, or host-mediated metabolic alterations can all result in dengue-related neurological issues. The three dengue vaccinations and the significance of meta-analyses for genetic data will also be covered. Finally, establish a connection with the microRNAs associated with dengue fever, creating new opportunities for the creation of dengue treatment regimens involving microRNAs.
Jan 2024
Drug-resistant tuberculosis (DR-TB) is the most urgent public health problem to solve in Peru, according to the Ministry of Health 1. In the WHO Global TB Report 2021, Peru has the highest burden of DR-TB in the Americas (Table 1), with 38% of TB cases either RR or MDR. In addition, the Ministry reports an estimated prevalence rate of DR-TB of 5.7% in new cases and 24.2% in previously treated cases. A total of 2493 new cases of DR-TB were reported in 2022, with 18.5% treatment dropout in 2019 believed to have increased by at least 52% in 2022 1. The post-pandemic context has created additional challenges for the control of DR-TB in Peru. A complex multiplicity of factors connects this disease to groups with high vulnerability, such as populations in extreme poverty and overcrowding or deprived of freedom; those who have immune system disorders, such as HIV and diabetes; and isolated indigenous populations.
Jun 2022 DOI 10.14302/issn.2328-0182.japst-22-4193
The strategy for safe drug discovery and development has limited clinical success as compared to wasted time and resources annually. This is due to the fact that the results of multiphase preclinical trials are less likely to make an accurate early prediction on the safety of test compounds to progress into the clinic as a valuable therapeutic agent. A lot of time and resources has been wasted in the multistage processes of drug discovery and development that does not work at the end of the procedure every year. During pre-marketing stage, for instance, the number of unsuccessful clinical trials are greater than the successful one because of safety issues. A toxicity study at different stages of preclinical and clinical trials is a routine procedure to investigate the undesirable side effects of test compounds being manifested on the natural processes of living things. It deals with the effect and mechanism of toxicity of test compounds that triggers different biological responses on different organ systems. The biological responses that would be manifested as a result of interaction between the receptors and active molecules of a test compound could be desirable pharmacological effect or undesirable side effect or both responses are manifested simultaneously depending on the selectivity or specificity of the molecule of a test compound for its receptor subtype which makes safe drug discovery and development very challenging. The response efficiency of the body (the net outcome of the body’s biological reaction against the side effect) would determine the potency of a test compound to manifest undesirable pharmacologic effect. In other words, the amount of a drug required to cause a biological harm or injury depends on the magnitude of the body’s biological reaction in which the immune response plays a great pharmacological role by neutralizing and harmonizing xenobiotics with the biological molecules. The dose of a test compound at 100 mg/kg body weight, for instance, could be lethal to some of the study animals while it is still non-lethal to some other study animals depending on the response efficiency of the body. The immune system is well connected to each and every biological systems of the body which allows it to detect undesirable side effects being manifested through immunoglobulins signalling and activation mechanisms. This complex communication network helps to localize the diverse side effects of a test compound being manifested on different organ systems into the immune system which makes a toxicity study relatively simple to monitor. The cellular immune system becomes active following the molecule-receptor interaction and start producing antibodies which is also known as immunoglobulins to protect bodily harm and destruction. Under normal biological circumstances, the amount of immunoglobulins produced by the cellular immune system following exposure to a test compound is proportional to the number of harmful molecules interacted with its receptor subtype. Thus, with the reference to the changes in the immune response against the administered dose, it would be able to deal with the diverse undesirable side effects of a test compound being manifested on treated study animals using computational systemic biology.
Jan 2022 DOI 10.14302/issn.2372-6601.jhor-22-4061
Background Human malignant cell models which reflect the structural and physiological complexity of tumor tissue are of great importance for preclinical research in oncology. Spheroids/tumoroids derived from solid tumors are of great interest as cellular models mimicking the first vascular-free growth phase of a tumor node. The fact of the identity between artificially created tumor multicellular aggregates and the real tumor tissue, however, needs to be specified, described and validated in order to see how closely the spheroids are biologically similar to the malignized tissues in vivo compared to the monolayer cell cultures traditionally used. We present here a comparison study of the characteristics of solid tumor cells of different histogenesis (melanomas, soft tissue sarcomas and bone sarcomas, epithelial tumors) cultured in two dimensions (monolayer culture) and three dimensional space (spheroid), namely: spatial organization, multiplication, metabolic activity. Patients and Methods For the creation of 2 D and 3D cell models the cells isolated from the patient's solid tumor fragments obtained intraoperatively were used. 15 samples of skin melanoma, 20 samples of soft tissue and osteogenic sarcomas (STBS), and 9 samples of epithelial tumors (ET). The tumor cells were all cultivated for at least 10 passages. We used phase contrast, confocal microscopy, and immunohistochemistry to investigate spheroids and monolayer cultures. The supernatants of tumor cells grown in 2D and 3D cultures were studied using ELISA and multiplex analysis for the production of a spectrum of chemokines and cytokines supporting the immunosuppression, invasion and metastasis processes. Results Tumor specimens received were predominantly of metastatic origin (75%). In 100% of cases 2D cultures were received, in 88.6% of cases (39 out of 44) we succeeded in obtaining spheroids. There was no direct correlation between the efficiency of tumoroid formation and the tumor's histogenetic origin and the stage of the cancer process (primary tumor, recurrence, metastasis). The median size of spheroids by 4-5 days of cultivation with a starting concentration of 10000 cells per well was 657.14 μm for melanoma (min 400 - max 1000 μm), 571.42 μm (min 400 - max 700 μm), 507.14 μm (min 300 - max 600 μm) for soft tissue sarcomas, 650.0 μm (min 400 - max 900 μm) for osteogenic sarcomas. Immunochemical analysis of Ki-67, GLUT1, and Ecadherin markers was carried out for tumor tissue samples, single-layer tumor cultures, and tumoroids of every patient. The distribution of the stained groups in the spheroids was distinct from the monolayer cultures and more in accordance with the distribution of such in the tissue tumor, the number of Ki-67+ cells was increasing in the spheroids. We detected no dependence of Ki-67+ and GLUT1+ cell localization grade on spheroid size. We identified E-cadherin in tumor tissue and tumoroids of breast carcinoma and one melanoma culture. Monolayer cultures did not express it. The increase in secretory cell activity of the solid tumor cells from 2D to 3D system was observed when CCL2, CCL3, CXCL1, CXCL16, MIF, IL10, MICA (p<0.01) were investigated. Conclusion The presence of patient-specific cells of solid tumors in a 3D environment causes activation of the proliferative and metabolic processes as compared to monolayer cultures, which makes these models approximate the real world clinical picture. The production of chemokines that can attract to the tumor various types of immune system cells, to include their immature versions, as well as production of cytokines and Immunosuppression factors that, when present in the tumor microenvironment in the high concentrations, contribute to the formation of immune cells having suppressive capacities occurs in the 3D cell system. Three-dimensional model of the initial tumor nodule formation stage thus demonstrates the forming process of tumor cells favorable for them microenvironment. Construction of three-dimensional models - spheroids of tumor cells of differing histogenesis demands individual approach and more thorough investigation.
Nov 2021 DOI 10.14302/issn.2690-4837.ijip-21-4015
Copper (Cu) has a strong impact on the function of the immune system through several different pathways. These impacts include helping the function of monocytes, neutrophils, and macrophages, and enhancing Natural Killer cells’ activities. Cu also has a role in antimicrobial properties and inflammatory response. It is also important for IL-2 production and response, which is a component of adaptive immune cells. Additionally, Cu has multiple roles in both proliferation and differentiation of T cells and is involved in the production of antibodies. Cu deficiency can even lead to "increased viral virulence"1. Copper has a long history of use in medicine, and has continued to be used for purification of water, including use in hospitals to prevent legionnaires disease. The CDC pre released information on a study completed in March 2020 on the lifespan of COVID-19 on different surfaces which included its lifespan on copper, where it was completely dead within 4 hours. In addition, "Several reports demonstrated that Cu deficiency weakens the human immune response" 2. Given the multiple avenues of impact, it has been suggested that Cu supplementation, within recommended levels, be given to individuals who are low in Cu to help them fight off COVID-19. It is also possible that Cu supplementation, within recommended levels, may help prevent COVID-19 infection, or help individuals who are not low in Cu to fight off COVID-19 infection. However, dosage would have to be carefully managed, as excess levels of Cu can lead to both neurodegenerative and neurodevelopmental diseases.
Mar 2021 DOI 10.14302/issn.2575-1212.jvhc-21-3767
Antibodies and antibody fragments, especially single-domain antibodies known as nanobodies, are important tools in diagnostics, research, and therapeutics. In a conventional antibody, light and heavy chains contribute to the formation of the antigen binding site. In addition to conventional antibodies, old and new world camels also have heavy-chain antibodies (hcAbs), which lack the light-chain antibodies that usually bind to the antigen, as well as single domain antibodies, the VHH domain, which are the smallest antigen-binding fragments and have high solubility, stability, and specificity. A VHH library against E. coli lipopolysaccharide (LPS) was produced using the camel immune system. E. coli strains from dead camel calves were isolated to extract the LPS and used to immunize a 2-year-old female camel. After isolating mononuclear lymphocytes for RNA extraction and amplification of the VHH gene, the PCR product was cloned into the pF1AT7 Flexi vector and transformed into JM109 E. coli competent cells by heat shock, resulting in a comprehensive VHHs library with 6.9 × 104 cfu/µg. The VHHs were expressed and screened with ELISA and PCR. Eleven colonies were positive by PCR, six of which were sequenced and submitted to Genbank compared with GenBank data to confirm the production of nanobodies with a similarity >90%.
Sep 2020 DOI 10.14302/issn.2694-2283.jsem-20-3539
The following document provides important information that everybody know about physical exercise as a means of managing COVID-19. It addresses the health benefits of physical exercise on our body’s immune system, and stress reduction. Already today in the entire world, coronavirus is now the leading causes of morbidity and mortality. It kills thousands of peoples per day worldwide and continues its impact on the governments and the society. Nowadays it is the greatest public health problem in most countries in the world. Since its identification on Jan, 7 by the chines scientists named the pathogen as a novel coronavirus. In the current situation COVID-19 is rapidly spreading worldwide and the number of cases and deaths are rising up speedily. The spread of the virus is a headache to the government in general and the society in particular. The nature of the virus disallowed contacting with one another, working together, meeting, and other activities the majority of government and private business organizations are enforced to discontinue their work. The growing burden of the virus would place millions of jobs at risk an additional 8.8 million people in working poverty around the world. The danger of the disease and loss of employment leads the majority at stress. A chronically stressed person impairs the organism’s ability to mount a strong immune response with a resultant increase in morbidity and mortality.
Aug 2020 DOI 10.14302/issn.2691-8862.jvat-20-3513
This paper explores the trends, issues and challenges confronting the successful vaccine development for the novel Coronavirus disease (COVID-19). Right from the commencement of the COVID-19 pandemic, no drugs or vaccine has been developed nor approved for treating those down with COVID-19. This year, the scientific community and the vaccine industry have been asked to respond urgently to SARS-COVID-2 pandemic. Presently numerous vaccine development platforms are under process and DNA- and RNA-based platforms showing great potential followed by recombinant-subunit vaccines. Through explorative research, it was established that companies involved in COVID-19 vaccine development are facing big challenges in the scientific, economic and logistical perspectives. Amongst these challenges are distrust, misinformation, and about understanding the immune system interaction with the vaccine being developed, as well as with the pathogen itself. Adjudged as insurmountable may be too early a conclusion. The race is on and progresses are being made. Proper understanding of trends, metrics and dynamics revolving around COVID-19 vaccine development is crucial in expanding possibilities for positive results from ongoing vaccine research. In this review, we spotlight on the most recent developments in COVID-19 vaccine, including top 10 early candidates that may hit the market in next few months.
Jun 2020 DOI 10.14302/issn.2372-6601.jhor-20-3372
Immune thrombocytopenia currently called under its’ new name, immune thrombocytopenic purpura (ITP) is a disease characterized by thrombocytopenia, in which the body attacks its own platelets due to the disorders in immune system. The pathophysiology of this disease includes increased platelet destruction and most megakaryocyte production in bone marrow. The most common clinical manifestation of ITP is mild or severe progressive bleeding that could result in death. ITP is generally named as primary or secondary ITP according to thrombocytopenia severity, disease duration, bleeding status and secondary occurrence of the disease. Currently for diagnosis, despite the blood count, antiglobulin test and laboratory tests that can detect platelet-bound antibodies, they are not enough for definitive diagnosis. Like the difficulty in diagnosis, ITP treatment is quite complicated which varies depending on age, characteristics and risk of the patient. It is classified as first, second and third-line treatment options. Also, depending on the condition of patients, combined treatment might be an option which increases the complexity of the treatment. Unfortunately, discussions related to different clinical applications in diagnosis and treatments continue recently. For this reason, we considered that preparation of a review containing recent updates in diagnostic approaches and treatment options in ITP will be remarkable and beneficial for physicians interested in this subject.
May 2020 DOI 10.14302/issn.2641-7669.ject-20-3313
Industrial effluents containing heavy metals may reach aquatic systems either through direct discharge or surface runoff and cause damage to aquatic organisms affecting their immune system and health. Hence the present study has been undertaken to observe the effects of hexavalent chromium on the WBCs of the fresh water fish, Labeorohita. WBCs play a major role in the immune response of the fish. For acute toxicity determination, healthy fish were subjected to static bioassays. The 24, 48, 72, and 96hr LC50 values were 50.88, 42.03, 28.09 and 10.87 ppm respectively. The fish were exposed to 0.5, 1, 1.5 and 2 ppm for 20 days. Differential count of WBCs and total WBC count were determined after every five days for twenty days. Lymphocytes exhibited a decline while the other cells and total WBC count exhibited an increase due to hexavalent chromium exposure. The results were subjected to two way analysis of variance.
May 2020 DOI 10.14302/issn.2692-1537.ijcv-20-3345
While the COVID-19 pandemic has raised concerns about the future of people worldwide, it has made it necessary to take measures with high economic costs, including quarantine. We consider it is more logical for some scientists to investigate time-saving treatment options until vaccination studies, which are started to be studied rapidly, are accomplished or specific antiviral agents are found. In this context, treatment combinations of one or more of the immune modulators known as cytokines, which can stimulate or accelerate the immune system, should be tried. In our opinion, although such options are not as effective as specific treatments such as vaccines, such options will offer highly effective alternatives in times of emergency. For this reason, we found it appropriate to make a reminder by preparing a broad review about interferon gamma, which is an antivirus and is an immunomodulator and which plays a critical role in humoral and cellular immunity.
Jun 2019 DOI 10.14302/issn.2690-0904.ijoe-19-2792
In deaths and diseases attributed to tobacco smoke cardiovascular events exceed cancer and respiratory diseases. Second hand smoke promotes the development of arteriosclerosis and can trigger acute changes of endothelial function and blood coagulability. Indoor smoking bans reduced coronary syndrome and myocardial infarction 10-20% within one year and were followed by sustainable decreases of stroke and diabetes. With a smoke-free hospitality industry people recognized tobacco smoke as an air pollutant, smoking in public was denormalized and social acceptance of smoking in front of children and pregnant women decreased also in homes and cars. Combined effects with ambient air pollution are proven for active smoking and suspected for SHS. Contamination with third hand smoke (THS) persists for months in homes and cars, creating secondary pollutants that in some cases are more toxic (e.g. nitrosamines). Remnants found in air, dust, and on surfaces (carpets, wallpapers, upholstery, soft toys) were associated with their metabolites in saliva of children and in urine of nonsmokers residing in homes previously occupied by smokers. In animal experiments effects of THS were found on thrombogenesis, insulin resistance through oxidative stress, on the developing immune system, lipid metabolism and alterations in liver, lung, skin and behavior. Much less is known about health effects for bystanders from the aerosols exhaled during “vaping” of e-cigarettes, but nicotine and other toxins from e-cigarettes are certainly a hazard, which should be prevented by the use of dermal and oral nicotine products, which are safer for nicotine replacement and without risk for bystanders.
May 2019 DOI 10.14302/issn.2324-7339.jcrhap-19-2746
Human immunodeficiency viruses causes HIV infection in humans belongs to two species of Lentivirus. It damages the cells of immune system which leads to weak immune system and the ability to fight from infections and diseases. This study was conducted to investigate the prevalence rate of HIV infection among pregnant women of different age groups attending Ajiko medical clinic, Damaturu, Nigeria. The prevalence rate was maximum (12.5%) in 36-45 age group and minimum (5%) in 26-35 age group but their was no HIV infection in 15-25 age group. The overall prevalence rate among pregnant women was 4%. General knowledge , training and campaigns of HIV prevention need to be tailored towards older women of age group 36-45 because of high prevalence rate.
Mar 2019 DOI 10.14302/issn.2641-5518.jcci-19-2664
Lenalidomide is a second generation immunomodulatory agent and a potent analogue of thalidomide that is FDA approved mainly for the treatment of multiple myeloma (MM) and transfusion-dependent anemia due to low or intermediate-1- risk myelodysplastic syndromes (MDS) associated with 5q deletion among other indications. Through its action on the immune system, lenalidomide alters the production of different cytokines ultimately resulting in immune activation against tumors. This immune activation may lead to collateral immune toxicities like fever, angioedema, Stevens-Johnson syndrome, tumor flare and others. Here we report a case of lenalidomide-induced high grade fever in a patient with MM and we summarize the literature about the physiology of such reaction and how to mitigate this adverse event.
Jan 2019 DOI 10.14302/issn.2572-3030.jcgb-18-2527
As remarkable advances have been made in immunotherapies, the overall goal of immunotherapy has become the selection of patients and evaluating the benefits of treatment. One of the major obstacles to develop immunotherapies is the lack of effective immune monitoring. Monitoring of key changes in the immune system during immunotherapy (immunomonitoring) provides important insights into efficacy as well as the immune mechanisms of response at the molecular and cellular levels. Immunomonitoring techniques include traditional immunoassays that use specific antibodies to recognize the analytes of interest, new high-throughput immunoassays that target immune cells and nucleic acids, and less classical immunogenomic approaches that rely on genome-wide profiling and computational analysis on various types of clinical samples. Substantial progress has been made in the application of immunomonitoring strategies to pre-clinical and clinical studies, especially for patients with cancer and infectious diseases. Current and emerging immunoassays performed in clinical practice will be examined herein, and immunogenomic approaches that complement these techniques will be highlighted and compared with traditional methods. Finally, we will discuss several new computational methods for analyzing gene signatures for immunomonitoring, including gene expression data profiling by microarray, the nCounter technique, regular RNA-seq, and single-cell RNA-seq. Novel immunomonitoring techniques, especially immunogenomic approaches, will continue to be developed to facilitate assessment of immunotherapeutic response and predict patient outcomes in cancer and infectious disease.
Dec 2018 DOI 10.14302/issn.2576-6694.jbbs-18-2489
Essential oils, called volatile oils or ethereal oils, are natural metabolic secretions of plants, the role of which is not yet fully understood by science. Some specialists consider them to be true plant hormones, fluid manifestations of the immune system of plants, in the sense that they contribute to the removal of pests, attracting, instead, pollinating agents, which are some insects and birds. Small, light–colored spherical structures, is, in fact, modified filaments, which behave like some secretory glands of essential volatile oils. They are the ones who give the fragrance of the aromatic plant and have, in the case of salvation, medicinal curative properties, such as fever reduction, blood cleansing, and relieving pain. Essential oils are products isolated from plants or organs through a physical process that have a certain volatility (higher or lower) and possesses an agreeable odour characteristic of the source from which they originate. They are also known as volatile or essential oils and their name are usually given by the popular name of the plant from which they are extracted. The most important characteristic of these mixtures, which also gives the special economic value, is the specific smell. This is the basis for their use in perfumery, cosmetics and the food industry. Many essential oils have special therapeutic qualities, some of which have been known and used since antiquity.
Oct 2018 DOI 10.14302/issn.2372-6601.jhor-18-2396
Although surgery is the main treatment for solid tumors, it could enhance the growth and metastasis of minimal residual cancer. In this review article we have discussed the perioperative changes in cancer cells and surrounding environment as well as the alterations in the immune system. Several trials are ongoing to develop new diagnostic and therapeutic options for minimal residual cancer after surgery.
Mar 2018
The crusade against cancer has a new army: immunotherapy. The rational design is very simple, but brilliant at the same time. Extract the patients T-cells, reprogram them in vitro for the expression of highly specific receptors against cancer, perfuse them back to the patient. As a result, T-cells are now instructed to selectively kill circulating tumor cells, while avoiding potential side effects. This ‘Fairy Tale’ however does not lack of drawbacks and limitations. First, malignant progression can be accompanied by profound immune suppression, which counteracts the immune system-mediated tumor elimination. Second, the immune cells modification does not match high standards in terms of safety for humans. Here, nanotech can fill these gaps, and help immunotherapy to be safer and more effective.
Aug 2017 DOI 10.14302/issn.2690-4721.ijcm-17-1676
Malaria is a mosquito-transmitted infectious disease caused by intracellular protozoan parasites of the genus Plasmodium. In the absence of prompt and appropriate treatment contraction of primary infection by a human being often represents a medical emergency since it may progress rapidly to life-threatening complications. Exposure to parasites activates the immune system resulting in, among other effects, the release of reactive oxygen intermediates (ROI). This has the potential to induce oxidative damage, thereby causing cellular destruction, and hence to have a severe effect on vital organs of the body. Overexpression of ROI leads to immunosuppression and is a causal factor in the development of malaria-related disease symptoms. However, the body possesses various defence mechanisms, notably including the production of antioxidants, which are capable of reducing the cellular effects of ROI. Antioxidants are either sourced exogenously from the diet or synthesized through different intracellular mechanisms. Antioxidants that include glutathione peroxidase, catalase, EDTA and vitamin C suppress the initial production of ROI. Others such as uric acid, superoxide dismutase and vitamin E may also inhibit potentially damaging products of ROI metabolism. Current anti-malarial drugs often have damaging side-effects, as exemplified by memory impairment following treatment for cerebral malaria. Recent studies have explored the potential use of antioxidants alone or in combination with anti-malarials as a therapeutic means to negate Plasmodium-induced oxidative stress and its associated metabolic complications. It is indicated that when utilized in an adjuvant capacity antioxidants of natural and synthetic origin may improve anti-malarial therapy by causing less damage to the host during malaria infection.
Jul 2017 DOI 10.14302/issn.2639-1716.jn-17-1495
Diets high in unsaturated fatty acids, especially those containing high levels of linoleic acid, e.g., corn oil, enhance mammary gland tumorigenesis in experimental animals. In contrast, diets high in long-chain polyunsaturated fatty acids such as eicosapentaenoic (EPA) and docosahexaenoic (DHA), e.g. menhaden oil, appear to have a suppressive effect on this tumorigenic process. Many mechanisms have been proposed to explain the tumor inhibitory action exerted by menhaden oil and other fish oils, e.g., differences in prostaglandin metabolism, energy efficiency, alterations of the immune system, changes in lipid peroxidation, etc. Fundamental to a mechanistic understanding of this phenomenon, however, is an understanding as to whether or not the tumor inhibitory activities of dietary fish oil is mediated via an inhibition of tumor cell proliferation or mediated via an enhancement of tumor cell loss. Whether the amount of dietary fat or the type of fat effects mammary tumorigenic processes, via an effect on tumor cell proliferation or tumor cell loss, has not been clearly established. In the studies described in this communication, three methods were utilized to study tumor cell proliferation, i.e., H3-thymidine autoradiographic analysis, 5-bromo 2'-deoxyuridine (Brdu) flow cytometric analysis, and proliferative cell nuclear antigen (PCNA) flow cytometric analysis. Two methods were used to study tumor cell loss, i.e., a determination of the I125Urd tumor emission rate and a determination of a cell loss factor from the formulas of Steel and Begg. The tumor examined was the human breast carcinoma cell line MDA- MB231 maintained in athymic nude mouse. No significant difference in cell proliferation between carcinomas of mice fed a high corn oil diet (20% w/w) and a diet high in fish oil (19% menhaden oil, 1% corn oil). In contrast, a significant (p<0.05) increase in the rate of I125Urd emission rate and cell loss factor from the carcinomas in the fish oil fed mice compared to the corn oil fed mice was observed. In summary, the decreased tumor volume in the human breast carcinomas maintained in athymic nude mice fed a fish oil diet as compared to those fed a corn oil diet, appears to be due, at least in part, to an increased rate of carcinoma cell loss rather than a decreased rate of carcinoma cell proliferation.
Jul 2016 DOI 10.14302/issn.2576-2818.jfb-16-1035
Female fertility is an economically important trait in the dairy industry, and the fertility selection index has been developed as a method of including female fertility in the breeding goals of this industry. This index considers a combination of factors, including days open, number of inseminations per lactation, success after first insemination, and pregnancy within 70 d, 90 d, and 110 d after parity. Based on a genome-wide association study of the fertility selection index using 442 Holsteins, we found that the index is influenced by a variation in the thioredoxin fold region of the family with the sequence similarity 213, member A (FAM213A) protein. FAM213A is a CXXC motif-containing peroxiredoxin 2-like protein that regulates cellular redox status. A replacement of isoleucine with valine in FAM213A was associated with poor fertility in cows. The overexpression of FAM213AVal in bovine endometrial epithelial cells reduced reactive oxygen species to a lesser extent relative to the overexpression of FAM213AIle and caused a decrease in cyclooxygenase-2 expression. Downregulation of cyclooxygenase-2 led to a decline in prostaglandin E2, which is critical for implantation because it protects the conceptus from the maternal immune system. Cows with FAM213AVal showed lower levels of prostaglandin E2 than did cows with FAM213AIle, suggesting that cows with FAM213AVal are less fertile than cows with FAM213AIle because of their reduced uterine environment. Thus, the present study found that FAM213A unexpectedly modulates female fertility in cattle.
Dec 2015 DOI 10.14302/issn.2324-7339.jcrhap-13-264
Phytochemicals (PHT) are a large group of biologically active plant chemicals that may have positive effects on human health such as immune system stimulation, down regulation of inflammatory responses, radical scavenging activities, cell repair function, and antibacterial and antiviral activity. In this proof of principle 6 months study, the effects of supplementing a PHT mix, Phyto V7, to HIV-1 seropositive individuals and AIDS patients were examined. Individuals with CD4+ T-cells below 350 counts/mm3were assigned to one of the following treatments: CG1 - no treatment, CG2 - only highly active antiretroviral treatment (HAART), TG1 - only Phyto V7, and TG2- both Phyto V7 and HAART. After 3 months of treatment there were approximately (-)1%, 1%, 2% and 4% increase in the mean weight of the CG1, CG2, TG1 and TG2 groups, respectively. The tendency for the body mass index (BMI) was similar. The CD4+ counts increased by 13%, 39%, 53% and 35%, respectively. Similar trends were noted after 6 months with 2%, 79%, 53% and 69% increases in the CD4+ counts, respectively. There was a significant reduction in viremia only in groups receiving HAART. Overall better results were obtained in the group of patients receiving both HAART and Phyto V7, in which the mean weight increased by 5.7% and the CD4+ T-cell counts increased by 69% after 6 months. This study indicates that providing Phyto V7 to HIV-1 seropositive individuals and AIDS patients, receiving or not receiving HAART, improves their physical wellbeing and CD4+ counts, enabling them to cope better with the viral infection.