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Apr 2023
Through T-cell engineering, researchers at the California South University (CSU) Cancer Research Institute (CRI) have shown that tumor growth can be stopped in a variety of cancers and prevented from spreading to other tissues. Findings from this study are the result of decades of research by Professor Ph.D. A. Heidari and our team of CSU, who discovered a protein called AH that can inhibit the growth and spread of cancer cells in several different ways. They become in the tissues of the body. The T cells were armed with MDA-7/AH to target cancer more widely. The engineering of T cells to produce MDA-7/AH causes cancer cells to be destroyed regardless of the expression of the target molecules. The tumor site is often very hostile to immune cells. It was found in the research that MDA-7/AH can help T cells proliferate and increase the number of cancer cells. The T cells were armed with MDA-7/ AH to target cancer more widely. The engineering of T cells to produce MDA-7/AH causes cancer cells to be destroyed regardless of the expression of the target molecules. The tumor site is often very hostile to immune cells. We discovered that MDA-7/AH can help T cells proliferate and increase the number of cancer cells.
Jun 2020 DOI 10.14302/issn.2691-8862.jvat-20-3417
Background Decreased antioxidant ability is one of the worsening conditions in AIDS.We aimed to evaluate total antioxidant ability among others, and their variation in HIV infected patients following their CD4+T cells count and viral load, in a context of new ART scarcity in most LMICs. Material and Methods We conducted a cross sectional study on 167 individuals (76 controls, 33 treatments naïve and 58 HIV-1 infected patients on ART). We assessed their plasma total antioxidant ability (FRAP), malondialdehyde (MDA) and thiol (SH) groups using standard spectrophotometric methods, then we calculated lipid peroxidation index (LPI). Statistical analysis was performed using GraphPad Prism 6. Data were analyzed by two-tailed unpaired t-test for two groups’ comparison and ANOVA for more than two groups. Pearson correlation between CD4+T cells count, viral load and the above markers was determined; P ≤ 0.05 was considered statistically significant. Results The following controls/naïve/treated subjects’ values for FRAP(mM) (1.907±0.074/1.77±0.05/1.695±0.03); MDA(μΜ) (0.781±0.081/1.115±0.118/ 1.342±0.109); SH (μΜ) (2.747±0.130/1.582±0.197/1.498 ±0.140)and LPI (0.43±0.61/ 0.61±0.7/2.59±0.83) were all obtained with P ≤ 0.05. The FRAP increased only with 3TC+TDF+EFV and 3TC+ABC+NVP cART while MDA decrease significantly with the later(p=0.027). MDA and LPI significantly increased in heavily treated patients with p<0.0014 and p=0.0001 respectively. overall, the patients showed an increase of viral loads following a decrease of CD4+T cells (r= -0.803, p=0.016) but 3TC+TDF+EFV seem to better manage the both. The only significant correlation was established between SH groups and CD4+Tcells count (r=0.447; p=0.0006); Conclusion Our study showed that thiol groups may be protective againstCD4+Tcells count depletion and that the cART 3TC+TDF+EFV, 3TC+ABC+NVP may be helpful in fighting against free radical generation and particularly 3TC+TDF+EFV as controlling CD4+Tcells count and viral load in long term treated patients. The study particularly showed the implication of cART in increasing lipid peroxidation index following the treatment duration in heavily treated patients, which aggravated their conditions in an area where drug options are limited, calling for new drugs availability and personalized medicine.
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.
Dec 2015 DOI 10.14302/issn.2471-2140.jaa-15-765
Reactive oxygen species (ROS) and reactive nitrogen species are believed to be one of the most important culprits in the pathogenesis of cardio/cerebrovascular diseases. Intensive researches have been conducted to target free radicals as potential treatment for cardio/cerebrovascular diseases. The 2-(((1,1-dimethylethyl) oxidoimino)-methyl)-3,5,6-trimethylpyrazine (TBN), a novel nitrone derivative of tetramethylpyrazine, has been demonstrated to exhibit significant therapeutic effects in ischemic stroke and Parkinson’s models due to its multiple functions, including calcium overload blockade and free radical-scavenging activity. In the present study, we found that TBN had significant radical trapping effect in cell-free assays. Additionally, TBN effectively blocked tert-butylhydroperoxide (t-BHP)-induced murine H9c2 cardiomyoblast cell death, suppressed H9c2 cell apoptosis and reversed the decrease in mitochondrial membrane potential. Furthermore, TBN markedly inhibited t-BHP-induced ROS generation and free radical NO and ONOO–.Taken together, these results suggest that TBN might be a potential candidate for the treatment of ischemic cardio/cerebrovascular diseases by targeting free radicals.
Feb 2026
Keratinocytes are pivotal in mediating cutaneous inflammation. Identifying anti-inflammatory factors within these cells holds promise for developing novel therapeutic strategies to manage skin inflammation. Transcription factor EB (TFEB) has recently emerged as a key regulator linking cellular energy metabolism to inflammatory processes, primarily through its influence on autophagy and NF-κB signaling. However, whether TFEB activation exerts anti-inflammatory effects in keratinocytes remains unclear. In vitro inflammation model was established in HaCat cells by incubation with proinflammatory mediators LPS and IL-1β. Cell viability and TFEB expression and phosphorylation were measured. The effect of TFEB activation by C1 and adenoviral TFEB overexpression on the expression of proinflammatory genes including COX-2, MCP-1 and IL-6 were detected. Also, IκBα protein level were determined. TFEB phosphorylation is increased while TFEB total protein expression is inhibited by treatment with LPS and IL-1β. Pharmacological activation of TFEB by compound C1 and TFEB overexpression suppressed the expression of COX-2, MCP-1 and TNF-α induced by LPS and IL-1β. TFEB overexpression increased basal IκBα expression and restored IκBα level under LPS treatment. TFEB knockdown reduced TFEB expression and lowered basal expression level of COX-2, MCP-1 and TNF-α. Our findings indicate that TFEB activation can mitigate inflammatory gene expression in keratinocytes triggered by LPS and IL-1β. This implicates TFEB as a significant novel modulator of cutaneous inflammation, highlighting its potential as a therapeutic target. Targeting TFEB could thus be a viable strategy for developing new treatments for chronic inflammatory skin conditions.
Jul 2023 DOI 10.14302/issn.2575-1212.jvhc-23-4510
Dermatophytosis affect companion animal’s skin and keratin appendages as cats and dogs, resulting in red, scaly, itchy, bald, and raised patches like ring. The three main groups are Microsporum, Trichophyton and Epidermophyton. This study collected samples of skin scrapping and hairs from 130 cats and 70 dogs, using common mycological approach samples were examined. Antifungal agar disc diffusion and broth microdilution assays were utilized on some of the isolates. Three groups of Guinea pigs (6 in each) were then infected with one isolate of M. canis or T. mentagrophytes fungi, another skin scrapping samples of virulent fungi was isolated on the 7th and 14th days, blood samples were collected at 14th day. Reverse transcription-PCR to detect 98 bp protease gene. Resulting in 45% of cats and dogs tested positive for Microsporum and Trichophyton species. Agar disc diffusion revealed that the antifungal medication griseofulvin was the most effective against tested isolates. The best results for MIC test were griseofulvin (0.98 µg/ml) followed by acetic acid (0.28 µg/ml). Differential leukocytic count of Guinea pigs showed that monocyte levels remained unchanged, while neutrophil and lymphocyte levels had increased. The active (isolates from Guinea pigs skin scrapping) and dormant cells (isolates from keratin free media) were distinguished by Reverse Transcriptase-PCR. Collectively, qPCR is a successive and feasible method for the diagnosis for Microsporum and Trichophyton species.
Nov 2022 DOI 10.14302/issn.2641-4538.jphi-22-4235
This study investigates the effect of Aqueous extract of abelmoschus esculentus on the microanatomy of the small, large intestine and stomach and the body weight of Wister rats. Twenty-one adults male wistar rats weighing between 100-120 grams were assigned into three groups consisting of seven rats each; Group A (control), Group B (low dose), and Group C (high dose). The rats in the control group were fed with fed with feed and water only while the rats in groups B and C were treated with 0.1mg/kg body weight and 3.0mg/kg body weight of abelmoschus esculentus respectively for 14 days. At the end of administration, the final weights of all rats were recorded before sacrifice using cervical dislocation and the small, large intestine and the stomach were harvested, processed and stained using H&E stain. The results were revealed as significant (p<0.05) increased in the mean body weight compared with the weight in the control groups and experimental groups. The treated animal groups revealed increased cellularity, focal metaplasia of the mucosal cells with villous disruption in the small intestine and dysplasia of the mucosal with loss of epithelial shape in large intestine. The stomach histology showed gastric pits with goblet cells smooth muscles layer and surface epithelium in the control group. Sections from the low dose treated group showed deep epithelical gastric pit areas with marked depletion of pits and goblet cells while the high dose treated group revealed dysplasia of gastric pits, goblet cells and smooth muscles appear mildly eroded.
Mar 2022 DOI 10.14302/issn.2641-5518.jcci-22-4096
Introduction Benign duodenocolic fistula (DCF), also known as a non-malignant fistula between the duodenum and colon, with or without cecum-involvement, is an unusual complication of different gastrointestinal (GI) diseases 12. Case This is a case of a 28-year-old Filipino female who presented with periumbilical pain for five months, with associated anorexia, fever, and weight loss. Biopsy showed chronic granulomatous inflammation with caseation necrosis and Langhan’s type giant cells consistent with tuberculous etiology (Figure 6 and Figure 7). Category I Anti-TB treatment for six months was started and the service planned to repeat both colonoscopy and CT-scan after the initial round of anti-TB treatment. Conclusion Benign duodenocolic fistula in the form of extrapulmonary TB is a rare GI finding that is triggered by inflammatory processes. Proper management in this case was to treat the underlying TB infection which is endemic in the Philippines.
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.
Jul 2021 DOI 10.14302/issn.2576-6694.jbbs-21-3819
The present study aimed to evaluate the effect of the Trivedi Effect®- Biofield Energy Treated/Blessed Test formulation/item (TI) composed of minerals (magnesium, zinc, copper, calcium, selenium, and iron), vitamins (ascorbic acid, pyridoxine HCl, alpha tocopherol, cyanocobalamin, and cholecalciferol), Panax ginseng extract, CBD isolates, and β-carotene on elasticity of skin, heart, muscle, and neuronal cells in the H9C2 (rat cardiomyocytes), C2C12 (mouse myoblast cells), HaCaT (human keratinocytes), and SH-SY5Y (human neuroblastoma cells) cell line in DMEM medium. The test formulation constituents were divided into two parts; one section was defined as untreated test formulation (UT), while the other portion of test formulation received Biofield Energy Healing/Blessing Treatment (BT) by a renowned Biofield Energy Healer, Mr. Mahendra Kumar Trivedi. The test items were treated with Biofield Energy Healing/Blessing Treatment and divided as Biofield Energy Treated/Blessed (BT) and untreated (UT) test items. MTT data showed that the test formulation in various concentrations was found as safe and nontoxic in the tested concentrations with viability range from 73% to 307%. Young’s modulus (YM) is a measure of cell stiffness, a decrease in YM value indicates increase elasticity of the cells and vice-versa. YM in H9C2 cells were decreased by 9.6% and 66.1% in the BT-DMEM + UT-TI group at 0.1 and 1 µg/mL respectively, as compared with untreated test group. However, C2C21 cells showed increased YM by 443.9% at 1 µg/mL in the UT-DMEM + BT-TI group, while 869.6% increased YM in the BT-DMEM + UT-TI group at 1 µg/mL as compared with untreated test group. However, 314% increased YM was reported in the BT-DMEM + BT-TI group at 1 µg/mL as compared with the untreated test group. However, the value of YM was significantly decreased in the HaCaT cell line by 247.7% (at 1 µg/mL), 225.8% (at 0.1 µg/mL), and 97.9% (at 1 µg/mL) in the UT-DMEM + BT-TI, BT-DMEM + UT-TI, and BT-DMEM + BT-TI group respectively, as compared with the untreated group. In addition, YM was significantly decreased in the SH-SY5Y cell line by 92.6%, 18.1%, and 26.6% at 1 µg/mL in the UT-DMEM + BT-TI, BT-DMEM + UT-TI, and BT-DMEM + BT-TI group respectively, as compared with the untreated group. Overall, the results showed the significant decreased YM among the SH-SY5Y, HaCaT, and H9C2 cells, while it was increased in the C2C21 cell line. Thus, the mechanical properties of cells such as cellular function, including shape, motility, differentiation, division, and adhesion to its surrounding extracellular matrix were improved. Overall, it can be useful in many disease progressions with improved cellular elasticity and its associated complications/symptoms.
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%.
Feb 2021 DOI 10.14302/issn.2372-6601.jhor-21-3733
Breast implant-associated anaplastic large cell lymphoma (ALCL) is a recently recognized type of T-cell lymphoma that can develop following breast implants, with morphologic and immunophenotypic features indistinguishable from those of ALK-negative ALCL. Here we report a case of a 58-year-old woman with a history of subglandular silicone implants placed for bilateral breast augmentation 25 years ago, who presented with bilateral breast pain and was found to have bilateral Baker Grade III capsular contracture, and heterogenous fluid collection centered near the left third costochondral articulation, a suspicious left chest wall lesion, and left axillary lymphadenopathy on imaging. A left axillary lymph node core biopsy and an aspiration of the fluid were performed, and no malignant cells were identified. The patient underwent bilateral removal of breast implants and total capsulectomies. Microscopic examination of the capsule surrounding the left breast implant revealed large pleomorphic tumor cells in a fibrinous exudate. By immunohistochemistry, the tumor cells were found to be positive for CD3 (subset), CD4, CD7, CD30 (strong and uniform), and CD43, and negative for CD2, CD5, CD8, and ALK1, supporting the diagnosis of breast implant-associated ALCL. No lymphoma cells were identified in the right breast capsule, confirmed by CD30 stain. Breast implant-associated ALCL is a very rare disease that can develop many years after breast implant placement. Proper evaluation with breast imaging and pathologic workup is essential to confirm the diagnosis in suspected cases. Our case highlights that adequate sampling is important in the investigation of patients with suspected breast implant-associated ALCL.
May 2020 DOI 10.14302/issn.2690-6759.jpar-20-3346
Coccidiosis in poultry is caused by protozoan parasites of the Eimeria species, which is responsible for worldwide economic losses. The aim of this study was to evaluated the therapeutic effect of NeemAzal® on Eimeria tenellain broiler Chickens as compared to Amprolium as a standard anticoccidial drug. A total of One Hundred and Sixty (160) broiler chicks were purchased, acclimatized and randomly divided into 4 groups (G1, G2, G3 & G4). G1 non-infected, non-treated (negative control), (G2) infected with 20000 E. tenella oocysts (positive control), (G3) infected and treated with Amprolium (Standard, 7 mg/kg b.w. for 5 days) and (G4) infected and treated with NeemAzal®200 mg/kg b.w. for 5 days). Evaluation was by clinical signs, performance data (weight gain, oocyst shed/gram faeces (OPG) and histopathology of the Caecum, Liver and Kidney. The data showed that birds infected with E. tenellahad an output of 1.3×105±3,333 oocysts per gram faeces on day 5 post inoculation. This output is significantly decreased to 0.37×105±3,111 oocysts in neem-treated birds. Infection with E. tenellainduced marked histopathological alterations in the caecum in the form of inflammation, vacuolation of the epithelium, and destruction of some villi. NeemAzal® decrease body weight loss of infected chickens. Moreover, the number of goblet cells stained with Hematoxylin and Eosin (H&E) within the infected villi was significantly lowered (P≤0.05). The results revealed that chicks of G1 had the best performance data compared to G2, G3& G4. In G3 & G4 there were a remarkable improvement in the data on performance, clinical signs, gross and microscopically caecal lesions compared to G2. Amprolium (G3) was shown to be superior to NeemAzal® (G4) compared to G2. NeemAzal® could be a good alternative for use as a coccidiostat to supplement the expensive anti-coccidiostats in the market.
Dec 2019 DOI 10.14302/issn.2372-6601.jhor-19-3092
Waldenström Macroglobulinemia (WM) is a B-cell lymphoproliferative disorder characterized mainly by uncontrolled accrual of M- immunoglobulin, secreted by malignant lymphoplasmatic cells. Mast cells interacting with malignant B-cells play an important role at the manifestation of the disease. Utilizing a previous xenotransplantation mouse model, this study evaluates long-term implant viability and quantifies distinct bone marrow mast cell populations along with their dynamics in non-WM and WM human bone implants. Non-WM bone implants were obtained from the femoral head of adult humans undergoing hip arthroplasty or hemiarthroplasty, whereas WM human bone implants originated from bone biopsies obtained from the posterior iliac crest of patients with active WM. All bone particles were implanted intramuscularly in twenty-four NOD/SCID mice. Following 3, 4 or 8 months postoperatively, xenografts were removed and studied using special histological techniques to identify mature and immature mast cells. Xenografts survived up to 8 months after implantation presenting normal cytoarchitecture (non-WM) or high-grade neoplastic infiltration and microresorption (WM bone biopsies). Statistical analysis of mast cell populations showed significant elevation regarding time progression and bone marrow microenvironment, thus suggesting the possible influence of malignant cells to the mast cell population in WM. This study presents the extended survival of intramuscular implantation of human adult bone xenografts into NOD/SCID mice and provides additional information on the interaction between mast cells and malignant B-cells.
Apr 2019 DOI 10.14302/issn.2578-8590.ipj-19-2772
Nociceptin/orphanin-FQ (NOCI) together with its receptor NOP are widely expressed in cortical and subcortical motor areas and it is known that NOCI acts as an anxiolytic attenuating the behavioral inhibition of animals acutely exposed to stressful/anxiogenic conditions. Influence of NOCI upon the dopaminergic system has been observed in the ventral tegmental area and in the nucleus accumbens as well as an inhibitory action of NOCI is described upon serotoninergic mechanisms at cells and terminal levels. In particular, it is known that serotoninergic fibers from the raphe system project to the substancia nigra (SN) and that this modulation is behaviourally relevant. In the present work, the effect of exogenous NOCI injected into the SN upon DA and 5-HT levels have been analyzed by means of differential pulse voltammetry and nafion-carbon fiber microelectrodes. Electrophysiological monitoring of multicell activity was concomitantly performed with the same microsensor. It appeared that both levels of these biogenic amines were specularly altered, with possibly a driving influence of the DA activity upon the serotoninergic function(s).
Nov 2018
Pre-adipocytes are the precursors with the potential to make new fat cells during adipose tissue expansion. Nevertheless, the pre-adipocytes behaviors, and their possible roles in energy homeostasis have long been overlooked. Our previous study implicates that interleukin-4 (IL-4) plays a positive metabolic role by promoting insulin sensitivity and inhibiting lipid accumulation. Besides, abundant evidence shows the involvement of matrix metalloproteinase-2 (MMP-2) in the process of adipose tissue expansion. The present study aimed at examining the cross talk among glucose, insulin and IL-4 on regulating MMP-2 expression and activity in 3T3-L1 pre-adipocytes. Effects of insulin and/or IL-4 on MMP-2 expression and activity were examined in pre-adipocytes under euglycemic or hyperglycemic environment by RT-PCR and gelatin zymography, respectively. Our results revealed that glucose level is a pre-requisite for pre-adipocytes responding to insulin and/or IL-4 treatment. In high glucose-containing environment, short-term acute insulin treatment (AI) and long-term chronic insulin exposure (CI) showed opposite regulation to MMP-2 expression and activity. Interestingly, the dominant MMPs regulatory role of CI under euglycemic condition was attenuated in cells exposed to high glucose concentration. Our results suggest pre-adipocytes may participate in the process of increasing adiposity, diabetic onset and diabetic complications through ECM alterations resulted from the insulin- and/or glucose- mediated changes of MMP-2 activity. The present study uncovers novel observations regarding pre-adipocytes behaviors.
Feb 2018 DOI 10.14302/issn.2639-1716.jn-18-1965
Lipomatous tumors are among the most common primary musculoskeletal neoplasms affecting both pediatric and adult patient populations. Patient age, tumor location, and imaging features all contribute to the differential diagnosis of musculoskeletal tumors. Tumors identified outside of common patient demographics or in unusual locations may lead to preoperative misdiagnosis. We present an uncommon adipocytic tumor occurring at an uncommon age which was proven at surgery to represent a preoperatively unexpected diagnosis. A 13 year old male presented with a fatty anterior proximal thigh mass; age and magnetic resonance findings suggested lipoblastoma. However, following complete surgical resection, histopathology confirmed hibernoma, a benign lipomatous tumor characterized by the presence of white and multivacuolated brown fat cells, the vast majority of which occur in adult patients.
Jan 2018 DOI 10.14302/issn.2575-1212.jvhc-17-1817
Chagas disease is zoonotic illness or an anthropozoonosis caused by flagellated protozoan parasite Trypanosoma cruzi. This infection presents alarming rates of incidence/prevalence, for this reason, is recognized worldwide as one of the 13 most neglected tropical diseases 1. Numerous studies have demonstrated the existence of domestic dogs infected with T. cruzi across endemic areas ranging from southern United States of America to Argentina 2. The reported prevalence varies widely (1.42-92%), depending on ecoepidemiological and sociocultural factors 3. It is important to emphasize that the natural infection in dogs with T. cruzi occurs in the same way as in humans, that is to say, through active transmission by vectors, contamination by feces infected with the parasite through wounds or the conjunctiva, can also occur by ingestion of infected vectors or tissues of wild animals present in the peridomicile or home 4. The transplacental transmission is also an important mode of transmission in dogs 5. Nevertheless, the main mode of transmission in canine species seems to be the ingestion of infected vectors 6. During the life cycle of T. cruzi the trypomastigotes present in the heces of the triatomines are introduced in the mammalian host by contamination of the insect bite or mucosal membranes. The metacyclic form can penetrate a variety of phagocytic and nonphagocytic nucleated cells. Once inside the cells the parasite becomes in amastigote, which are multiplicative forms that divide into cells. Due to the high parasitic load they produce the lysis of the cells and escapes into the cytoplasm. The amastigotes transform to slender trypomastigotes which can invade adjacent cells, this forms can be ingested by triatomines and they transform into epimastigotes Finally, after migration to the bug's hindgut, the epimastigotes differentiate into infectious metacyclic trypomastigotes, in this way the life cycle of this microorganism is completed 7.
Jan 2018
Breast cancer is the most common cancer in women worldwide. In the United States, is the second leading cause of cancer deaths in women. In Puerto Rico between 2008 and 2012, breast cancer was the most diagnosed type of cancer and the leading cause of cancer deaths among women. This is a case of 54 years old female diagnosed with stage IV right breast carcinoma. The patient complaints were weakness and a right breast ulcer. She started a metabolic correction therapy, which consisted of high intravenous vitamin C infusions, a nutritional supplementation plan, and Paleolithic diet. During treatment, both Glycohemoglobin and Carcinoembryonic Antigen levels decreased significantly, the right breast ulcer decreased in size, and the patient’s quality of life improved. Over the years, vitamin C studies have demonstrated a cytotoxic action against malignant cells. Based on the results from this case, we advocate continue studying possible adjuvant treatments for cancer patients, involving IV infusions of vitamin C and metabolic correction plans.
Aug 2017 DOI 10.14302/issn.2575-1212.jvhc-17-1662
Immunization of cattle with the bacillus Calmette-Guérin (BCG) vaccine, especially neonates, induces protection against Mycobacterium bovis (M. bovis) and has been proposed as a strategy for bovine tuberculosis (bTB) control. Therefore, the aim of this study was to evaluate the immune response induced under field conditions in neonatal calves vaccinated with BCG Phipps, a strain that has rarely been evaluated in the bovine population, using interferon (IFN)-γ and tuberculin tests, flow cytometry and enzyme-linked immunosorbent assay. Two groups (vaccinated and control) of 5 calves were monitored for 12 weeks, and increases in the in vitro IFN-γ production, the percentage of cluster of differentiation (CD)8+ T cells and the activation levels of CD4+ and CD8+ T cells were observed 3 to 4 weeks post-vaccination. Bovine purified protein derivative-specific IFN-γ production was increased about 4.8- and 5.5-fold in vaccinated animals compared to non-vaccinated animals 3 and 4 weeks post-vaccination respectively. CD8+ T cells of the vaccinated group were increased 1.6-, 1.5- and 1.6-fold at weeks 2, 3 and 4 respectively. Levels of activation were 1.7- and 1.9-fold higher for CD4+ T cells and 2.3- and 1.8-fold higher for CD8+ T cells in the vaccinated group at weeks 3 and 4 respectively in response to M. bovis antigens. However, no animals (vaccinated or control) showed positive results for the single intradermal comparative tuberculin test (SICTT). Therefore, our results indicate that vaccination with M. bovis BCG Phipps strain stimulated peripheral blood T cell activity and induced a cell-mediated immune response. In addition, vaccination did not interfere with the SICTT, as previously reported, which indicates that this vaccine could be successfully applied in bTB control campaigns.
Jul 2017 DOI 10.14302/issn.2372-6601.jhor-17-1473
Objective: This study aimed to evaluate the relation of Lactate dehydrogenase (LDH) levels with stage of the disease and it role in monitoring tumor response to therapy in lymphoma patients. Methods. LDH levels were evaluated on 65 diagnosed Algerian children and compared to healthy control. Results: Our results revealed that LDH levels were significantly higher in untreated children with both hodgkin’s and non hodgkin’s lymphomas compared to control. Moreover, it was observed that the higher is the stage of disease, the more serum LDH level will be. However, there was a significant fall in serum LDH activity by completion of the chemotherapeutic courses. Conclusion: LDH plays an important role in tumor initiation and maintenance. The elevated serum LDH may reflect, release of the enzyme from malignant cells and suggest that they may reflect tumor burden and therefore correlate with disease progression.
Jul 2017 DOI 10.14302/issn.2575-1212.jvhc-17-1586
The mammary tumor is one of the most common cancer in female dogs and, at the present days, there is a big focus on the study of the relation between this kind of tumor in animals and the cells that stay around them, like the inflammatory cells. The objective of this study was to evaluate and show where the inflammatory cells stay in simple mammary carcinomas in female dogs by immunohistochemistry. Samples of simple mammary carcinomas (tumor group; n=26) and mammary gland samples without tumor (control group; n=18) were submitted to immunohistochemical analysis for the detection of T lymphocytes, macrophages, plasma cells and the MHC-II molecule. The mast cells were evaluated by the histochemical technique (toluidine blue). Lymphocytes, macrophages and mast cells were observed distributed in the tumor stroma. MHC-II was detected in tumor cells and in the inflammatory infiltrate. Plasma cells predominated in the peritumoral stroma. Macrophages differed significantly between the two groups and predominated in the tumor group. In the comparison between histological types of mammary carcinomas, mast cells differed significantly between solid tumors of the tubular / papillary types. The cytoplasmic immunodetection of MHC-II was suggested an inefficient antigen presentation. Some of the leukocytes present in the tumor infiltrate, appear to be exerting a pro-tumor effect and allowing the progression of tubular and papillary carcinomas. But in solid carcinomas (may be poorly immunogenic), as they had the lowest proportion of leukocytes present in the tumor site. More studies are necessary to confirm these results, such as the determination of the cytokine profile and the predominant leukocyte subpopulations in the tumor microenvironment.
Jun 2017 DOI 10.14302/issn.2690-4721.ijcm-17-1533
This essay draws on recent evidences from SIV vaccination studies in rhesus macaques to argue for the potential importance of HIV-1-specific CD8+ T cells restricted by the non-classical major histocompatibility complex, HLA-E, in controlling HIV-1 replication. It then seeks to present a possible method of inducing such responses through the procedure of T cell vaccination using activated autoimmune CD4+ T lymphocytes ‘infected’ with inactivated replication-incompetent structurally intact HIV-1 particles. It is hoped that the argument presented here will interest many of those involved in HIV/AIDS research and others in the general scientific community.
Jun 2017 DOI 10.14302/issn.2471-2175.jdrt-17-1481
Background: Studies have unveiled lower levels of serum vitamin D in autoimmune diseases and the role of vitamin D in inhibition of helper T cells proliferation, stimulation of regulatory T cells, diminishing of B-lymphocyte differentiation and inhibition of immunoglobulin secretion has been discussed in the literature. Oral lichen planus (OLP) is an autoimmune mucocutaneous disorder in which cell mediated immunity plays an important part and so it may also be related to serum vitamin D levels. Aim: To estimate serum vitamin D in oral lichen planus patients of North India, compare it to the controls and to evaluate various factors influencing vitamin D level in OLP cases such as sun exposure, gender, psychosocial factors, meteorological influences, religion and diet. Methods and Material: Venous blood samples of 102 clinically diagnosed oral lichen planus patients and 102 age and sex matched controls were obtained for the study and serum vitamin D levels were estimated using Vitek Immunodiagnostic Assay System, an automated bench-top immuno-analyzer, based on the Enzyme Linked Fluorescent Assay. The data was analyzed using chi-squared test and t-test. Results: Mean vitamin D in OLP cases and controls was 20.40 ng/ml and 32.67 ng/ml respectively. Vitamin D3 deficiency was more in OLP cases (70.6%) as compared to controls (34.3%) and insufficiency was more in controls (35.3%) as compared to OLP cases (16.7%). These differences were statistically significant. Conclusion: Although vitamin D deficiency was found more in OLP cases pointing towards the possible co-relation of vitamin D and OLP, yet insufficiency was seen more commonly in controls which revealed that this important vitamin was lacking in North Indian population.
Apr 2017 DOI 10.14302/issn.2372-6601.jhor-17-1463
Melanoma is considered to be a very aggressive cancer due to its rapid growth, early and multiple metastases and limited response to standard treatment. Many researchers have hypothesized that the combination of radiation therapy and immunotherapy in the treatment of melanoma primary tumors and metastases improves the efficiency of these methods as compared to their use separately. Therefore, combined therapy is an increasingly popular topic in radiation oncology. Although the mechanism of immune response to ionizing radiation remains unclear, known are the factors involved in the immune response, including NK and CD8(+) T cells. Many studies have demonstrated the importance of inflammatory factors, primarily cytokines, in the response to ionizing radiation. In turn, many cytokines released in an irradiated organ, such as tumor necrosis factor α (TNFα), interleukins IL1 and IL6 and transforming growth factor beta (TGFβ), can induce the production of significant amounts of reactive oxygen species that are associated with the induction of DNA damage in tumor cells. In relation to anticancer immunotherapy, the clinical data obtained to date can encourage future studies combining radiation therapy and the inhibitors of cell division checkpoints in the treatment of advanced melanoma. In a recent study, melanoma cell lines became more sensitive to radiation after BRAF inhibition, which provides a potential synergistic mechanism of BRAF inhibitor (BRAFi) combined with radiation therapy for better effects of treatment. In this article, we present a systematic review of the literature on the use of the combination of radiation therapy and immunotherapy in the treatment of melanoma.
Feb 2016 DOI 10.14302/issn.2372-6601.jhor-15-822
Small interfering RNA (siRNA) based drugs for overcoming multiple drug resistance of hematological malignancies could solve the problem of poor response to the chemotherapy and hight relapse rate. The main factor that significantly limits biomedical application of siRNA is inefficient delivery to target cells and tissues. The attachment of siRNA to molecules, which enter into the cell by natural transport mechanisms, can improve cellular uptake of siRNA. In current study the carrier-free cellular uptake of siRNA containig cholesterol residues conjugated to the 5’-end of the sense strand via oligomethylene linker of various length (here and after Ch-siRNA) was explored. The data demonstrate that cholesterol residue increase the accumulation of siRNA in all tested cell lines and the primary cells. The efficiency of Ch-siRNA accumulation in K562 cells depends greatly on the leangth of the linker connecting cholesterol and siRNA: Ch-siRNAs with linker of 10 - 12 methylene units accumulate the most efficiently in this cells. It was found that Ch-siRNA effectively accumulates in MOLT-3 (acute lymphoblastic leukemia, ALL), HL-60 (acute myelogenous leukemia, AML), K562 (chronic myelogenous leukemia CML) and primary peripheral blood mononuclear cells (PBMC) from patient with non-Hodgkin lymphoma (NHL) or healthy donor resulting in near 100% of transfected cell when used at 1 mM concentration.
Jan 2015 DOI 10.14302/issn.2379-7835.ijn-14-606
Telomeres are strings of DNA that are not themselves genes but that extend every chromosome beyond its last gene. Terminal telomeres are sacrificed during every mitotic event in human cells (“telomere attrition”), preserving the functional genome despite the “end replication problem.” However, the “telomeric theory of biological aging” suggests that when an individual cell has reproduced itself a sufficient number of times (the “Hayflick limit”), some the its telomeres have become critically shortened (“telomeric crisis”) and cannot completely “cap off” a chromosome, and any further attempts to replicate such a chromosome would produce damaged DNA and a dysfunctional cell (“cellular aging”). As cells enter telomeric crisis, they usually initiate intracellular signaling cascades that arrest DNA replication and mitotic activity, converting biologically active cells into inactive cells (“cellular senescence”). The progressive accumulation of senescent cells impairs the healthy functioning of tissues and produces “biological aging.” Oxidative stress damages telomeres and accelerates telomere attrition and biological aging. Premature biological aging is associated with degenerative diseases and diminished quality of life. Reducing the level of systemic oxidative stress can ease the oxidative drive toward cellular senescence and premature biological aging. Increased intakes of antioxidant-rich foods and specific antioxidant nutrients (such as fruits and vegetables, α -lipoic acid, astaxanthin, eicosapentaenoic acid, docosahexaenoic acid, trans-resveratrol, N-acetylcysteine, methylsulfonylmethane, lutein, vitamin C, vitamin D, vitamin E, and γ-tocotrienol) may decrease cellular and systemic oxidative stress and decelerate biological aging.
Apr 2014 DOI 10.14302/issn.2377-2549.jndc-13-329
The aim of the study was to synthesize sub-100nm poly-ε-caprolactone nanoparticles (PCL NP), load them with the mycobacterial protein, ESAT 6 and study the resulting immune responses in CD4+ and CD8+ T cells when incubated with human peripheral blood monocyte derived macrophages that had internalized the PCL NP. The synthesized PCL NP were characterized for size, shape and charge. They were found to be about 60nm in size with spherical shape. MTT assay revealed that the particles were perfectly biocompatible when tested in vitro on THP1 human monocytic cell line. The particles had a slow protein release kinetics and did not degrade appreciably even after 30 days in buffer solution. ELISA was used to quantify the cytokine response of CD4+ and CD8+ T cells when incubated with the monocyte derived macrophages as antigen presenting cells. The result of antigen presentation assay revealed that the antigen loaded PCL NP enhanced Th1 and CD8+ T cell responses significantly compared to the pure antigen. Thus we conclude that PCL NP of 60nm size can be effectively tested as a vaccine adjuvant with resulting activation of Th1/Th2 immunity as well as cytotoxic T cell response.