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1.
Eur J Haematol ; 109(5): 494-503, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35871389

RESUMO

OBJECTIVES: The benefits and risks of thromboprophylaxis usage in patients with advanced cancer at the end of their lives remain unknown, especially with the lack of randomized studies. This study aimed to describe the clinical use of thromboprophylaxis in those patients under palliative care. METHODS: A retrospective cohort study. It was performed on patients admitted to the Palliative Care Center. RESULTS: A total of 719 patients were enrolled in the study. The mean age was 62.97 (13.65) years. Venous thromboembolism (VTE) incidence was 5.4% (n = 39). At the time of admission, 31.29% (n = 225) of patients were on thromboprophylaxis. At death time, 17.5% (n = 126) of patients were on thromboprophylaxis (41.3% on primary and 58.7% on secondary thromboprophylaxis). The incidence of clinically suspected fatal VTE was 6.5% (n = 47). Surprisingly, clinically suspected VTE was higher statistically in patients with thromboprophylaxis rather than in non-thromboprophylaxis (p < .001). By using linear regression, only higher PPI scores on admission were independent negative predictors of length of stay (OR:4.429, 95% CI: 5.460-3.398, p < .001). The development of clinically suspected fatal VTE, whatever the status of thromboprophylaxis, did not affect the length of stay. CONCLUSIONS: Thromboprophylaxis does not decrease the risk of clinically suspected fatal VTE in patients with advanced disease in their terminal phase. Patients with poor performance status and a short prognosis are unlikely to benefit from thromboprophylaxis.


Assuntos
Neoplasias , Tromboembolia Venosa , Anticoagulantes/uso terapêutico , Humanos , Pacientes Internados , Pessoa de Meia-Idade , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Cuidados Paliativos , Estudos Retrospectivos , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controle
2.
Kidney Blood Press Res ; 47(2): 81-93, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35158353

RESUMO

INTRODUCTION: Diabetic kidney disease (DKD) remains the leading cause of chronic kidney disease. Dysregulation of circulating miRNAs has been reported, suggesting their pathological roles in DKD. This study aimed to investigate differentially expressed miRNAs in the sera of type 2 diabetes mellitus (T2DM) patients with and without albuminuria in a selected Malaysian population. METHOD: Forty-one T2DM patients on follow-up at a community clinic were divided into normo-(NA), micro-(MIC), and macroalbuminuria (MAC) groups. Differential levels of miRNAs in 12 samples were determined using the pathway-focused (human fibrosis) miScript miRNA qPCR array and was validated in 33 samples, using the miScript custom qPCR array (CMIHS02742) (Qiagen GmbH, Hilden, Germany). RESULTS: Trends of upregulation of 3 miRNAs in the serum, namely, miR-874-3p, miR-101-3p, and miR-145-5p of T2DM patients with MAC compared to those with NA. Statistically significant upregulation of miR-874-3p (p = 0.04) and miR-101-3p (p = 0.01) was seen in validation cohort. Significant negative correlations between the estimated glomerular filtration rate (eGFR) and miR-874-3p (p = 0.05), miR-101-3p (p = 0.03), and miR-145-5p (p = 0.05) as well as positive correlation between miR-874-3p and age (p = 0.03) were shown by Pearson's correlation coefficient analysis. CONCLUSION: Upregulation of previously known miRNA, namely, miR-145-5p, and possibly novel ones, namely, miR-874-3p and miR-101-3p in the serum of T2DM patients, was found in this study. There was a significant correlation between the eGFR and these miRNAs. The findings of this study have provided encouraging evidence to further investigate the putative roles of these differentially expressed miRNAs in DKD.


Assuntos
Diabetes Mellitus Tipo 2 , MicroRNAs , Albuminúria , Biomarcadores , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/genética , Humanos , Malásia
3.
Int J Mol Sci ; 23(19)2022 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-36232660

RESUMO

Breast cancer-related lymphedema (BCRL) is a form of secondary lymphedema that is characterized by abnormal swelling of one or both arms due to the accumulation of lymph fluid in the interstitial tissue spaces, resulting from obstruction of the lymphatic vessels due to surgery insults, radiotherapy, or chemotherapy. Due to the multifactorial nature of this condition, the pathogenesis of secondary lymphedema remains unclear and the search for molecular factors associated with the condition is ongoing. This study aimed to identify serum microRNAs and adipokines associated with BCRL. Blood was collected from 113 breast cancer survivors and processed to obtain serum for small RNA-sequencing (BCRL vs. non-BCRL, n = 7 per group). MicroRNAs that were differentially expressed (fold change >1.5, p < 0.05) between lymphedema cases and those without lymphedema were further quantified in a validation cohort through quantitative reverse transcription PCR (BCRL n = 16, non-BCRL, n = 83). Leptin and adiponectin levels were measured in a combined cohort (BCRL n = 23, non-BCRL n = 90) using enzyme-linked immunosorbent assays. Two of the most significantly upregulated microRNAs, miR-199a-3p and miR-151a-3p, were strongly correlated with the onset of lymphedema and diabetes mellitus in the BCRL group. Leptin levels were higher in the BCRL cohort compared to the non-BCRL cohort (p < 0.05). A metabolic syndrome biomarker, the adiponectin/leptin ratio, was found to be lower in the BCRL group than in the non-BCRL group (median: 0.28 vs. 0.41, p < 0.05). Extensive studies on the mechanisms of the identified microRNAs and association of leptin with arm lymphedema may provide new insights on the potential biomarkers for lymphedema that should be followed up in a prospective cohort study.


Assuntos
Neoplasias da Mama , Sobreviventes de Câncer , MicroRNA Circulante , Linfedema , Adipocinas , Adiponectina , Braço/patologia , Neoplasias da Mama/complicações , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Feminino , Humanos , Leptina , Excisão de Linfonodo/efeitos adversos , Linfedema/genética , Estudos Prospectivos
4.
Saudi Pharm J ; 30(6): 815-824, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35812146

RESUMO

Thiosemicarbazones have received noteworthy attention due to their numerous pharmacological activities. Various thiosemicarbazone derivatives have been reported to play a key role as potential chemotherapeutic agents for the management of cancer. Herein, we aimed to establish the anticancer efficacy of novel thiosemicarbazone derivative C4 against colon cancer in vitro. The MTT viability assay identified C4 as a promising anticancer compound in a panel of cancer cell lines with the most potent activity against colon cancer cells. Further, anticancer potential of C4 was evaluated against HT-29 and SW620 colon cancer cell lines considering the factors like cell adhesion and migration, oxidative stress, cell cycle arrest, and apoptosis. Our results showed that C4 significantly inhibited the migration and adhesion of colon cancer cells. C4 significantly increased the intracellular reactive oxygen species (ROS) and induced apoptotic cell death. Cell cycle analysis revealed that C4 interfered in the cell cycle distribution and arrested the cells at the G2/M phase of the cell cycle. Consistent with these results C4 also down-regulated the Bcl-XL and Bcl-2 and up-regulated the caspase-3 expression. These findings introduced C4 as the potential anticancer agent against colon cancer.

5.
BMC Cancer ; 21(1): 709, 2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34130642

RESUMO

BACKGROUND: Though sepsis is common in patients with cancer, there are limited studies that evaluated sepsis and septic shock in this patient population. The objective of this study was to evaluate the outcomes and to identify predictors of mortality in cancer patients admitted to the intensive care unit (ICU) with septic shock. METHODS: This was a retrospective study conducted at a medical-surgical oncologic ICU of a comprehensive cancer center. Adult cancer patients admitted with septic shock between January 1, 2008 and December 31, 2019 were enrolled. Septic shock was defined as an ICU admission diagnosis of sepsis that required initiating vasopressors within 24 h of admission. Patient baseline characteristics, ICU length of stay and ICU and hospital mortality were recorded. Univariate analysis and logistic regression were performed to identify predictors associated with ICU and hospital mortality. RESULTS: During the study period, 1408 patients met the inclusion criteria. The mean age was 56.8 ± 16.1 (SD) years and mean Acute Physiology and Chronic Health Evaluation (APACHE) II was 23.0 ± 7.91 (SD). Among the enrolled patients, 67.8% had solid tumors while the remaining had hematological malignancies. Neutropenia and thrombocytopenia were reported in 19.3 and 39.5% of the patients, respectively, and mechanical ventilation was required for 42% of the patients. Positive cultures were reported in 836 (59.4%) patients, most commonly blood (33%) and respiratory (26.6%). Upon admission, about half the patients had acute kidney injury, while elevated total bilirubin and lactic acid levels were reported in 13.8 and 65.2% of the patients, respectively. The median ICU length of stay was 4 days (IQR 3-8), and ICU and hospital mortality were reported in 688 (48.9%) and 914 (64.9%) patients, respectively. Mechanical ventilation, APACHE II, thrombocytopenia, positive cultures, elevated bilirubin and lactic acid levels were significantly associated with both ICU and hospital mortality. CONCLUSIONS: In a relatively large cohort of patients with solid and hematological malignancies admitted to the ICU with septic shock, hospital mortality was reported in about two-third of the patients. Mechanical ventilation, APACHE II, thrombocytopenia, positive cultures, elevated bilirubin and lactic acid levels were significant predictors of mortality.


Assuntos
Choque Séptico/mortalidade , Estado Terminal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida , Fatores de Tempo , Resultado do Tratamento
6.
Mediators Inflamm ; 2020: 9560684, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32322167

RESUMO

Human gut is home to a diverse and complex microbial ecosystem encompassing bacteria, viruses, parasites, fungi, and other microorganisms that have an undisputable role in maintaining good health for the host. Studies on the interplay between microbiota in the gut and various human diseases remain the key focus among many researchers. Nevertheless, advances in sequencing technologies and computational biology have helped us to identify a diversity of fungal community that reside in the gut known as the mycobiome. Although studies on gut mycobiome are still in its infancy, numerous sources have reported its potential role in host homeostasis and disease development. Nonetheless, the actual mechanism of its involvement remains largely unknown and underexplored. Thus, in this review, we attempt to discuss the recent advances in gut mycobiome research from multiple perspectives. This includes understanding the composition of fungal communities in the gut and the involvement of gut mycobiome in host immunity and gut-brain axis. Further, we also discuss on multibiome interactions in the gut with emphasis on fungi-bacteria interaction and the influence of diet in shaping gut mycobiome composition. This review also highlights the relation between fungal metabolites and gut mycobiota in human homeostasis and the role of gut mycobiome in various human diseases. This multiperspective review on gut mycobiome could perhaps shed new light for future studies in the mycobiome research area.


Assuntos
Microbioma Gastrointestinal/fisiologia , Bactérias/metabolismo , Fungos/metabolismo , Fungos/fisiologia , Microbioma Gastrointestinal/genética , Humanos
7.
Adv Exp Med Biol ; 1292: 97-112, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32542457

RESUMO

Colorectal carcinoma (CRC) is a malignancy of epithelial origin in the large bowel. The elucidation of the biological functions of programmed cell death ligand-1 (PD-L1), thymidylate synthase (TYMS), and deleted in colorectal cancer (DCC) biomarkers including their roles in the pathophysiology of CRC - has led to their applications in diagnostic and chemo-pharmaceutics. We investigated whether PD-L1, TYMS, and DCC protein expression in CRC tumors are predictive biomarkers of treatment outcome for CRC patients. The expressions of PD-L1, TYMS, and DCC were evaluated by immunohistochemistry (IHC) in 91 paraffin-embedded samples from patients who underwent colectomy procedure in Hospital Serdang, Selangor, Malaysia. There was high expression of DCC in most cases: 84.6% (77/91). PD-L1 showed low expression in 93.4% (86/91) of cases and high expression in 6.6% (5/91) of cases. Low and high expressions of TYMS were detected in 53.8% (49/91) and 46.2% (42/91) of the CRC cases, respectively. There was a significant association between the TYMS expression and gender (P < 0.05); the expression of TYMS was observed at a high level in 76.2% of males and in 23.8% of females. The mean overall survival (OS) was 100 months for the CRC patients evaluated. The OS for patients with high expression of PD-L1 was 22 months. Patients with high expression of TYMS and DCC showed OS of 90 and 96 months, respectively. The results from this study suggest that PD-L1, TYMS, and DCC expression could be used as biomarkers to stratify CRC patients who could benefit from adjuvant therapy.


Assuntos
Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/análise , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Receptor DCC/metabolismo , Timidilato Sintase/metabolismo , Antígeno B7-H1/biossíntese , Receptor DCC/biossíntese , Feminino , Humanos , Imuno-Histoquímica , Masculino , Timidilato Sintase/biossíntese , Resultado do Tratamento
8.
J Fish Dis ; 43(10): 1249-1258, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32830331

RESUMO

Groupers are popular aquaculture species in South-East Asia, but their cultivation is affected by infectious disease outbreaks. Mucosa-associated lymphoid tissues provide a first-line defence against pathogens; however, few studies are available relating to cellular or proteomic responses of mucosal immunity in grouper. Skin, gill and intestine were sampled from brown-marbled grouper Epinephelus fuscoguttatus (Forsskål, 1775) at 4 and 96 hr post-infection (hpi) and 7 days post-infection (dpi) following intraperitoneal infection with Vibrio harveyi, and stained with haematoxylin/eosin and Alcian Blue/periodic acid-Schiff. Skin mucus was analysed by 2D-gel electrophoresis, and proteins modulated by the bacterial infection identified. In the infected fish, significant increases in sacciform cells in skin and increased levels of nucleoside diphosphate kinase in mucus were detected at 4 hpi. At 96 hpi, goblet cells containing acidic mucins significantly increased in the intestine, while those containing mixed mucins increased in skin and gills of infected fish. Proteasome subunit alpha type-I and extracellular Cu/Zn superoxide dismutase levels also increased in mucus. Rodlet and mast cells did not appear to respond to the infection. Mucosal tissues of grouper appeared actively involved in response to Vibrio infection. This information may help future research on improving grouper health, production and vaccine development.


Assuntos
Bass/imunologia , Doenças dos Peixes/imunologia , Imunidade nas Mucosas , Vibrioses/veterinária , Animais , Bass/microbiologia , Doenças dos Peixes/microbiologia , Células Caliciformes/microbiologia , Mucosa/microbiologia , Mucosa/patologia , Muco , Proteoma , Vibrio , Vibrioses/imunologia
9.
BMC Biotechnol ; 19(1): 27, 2019 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-31088425

RESUMO

BACKGROUND: The current limitations of conventional BCG vaccines highlights the importance in developing novel and effective vaccines against tuberculosis (TB). The utilization of probiotics such as Lactobacillus plantarum for the delivery of TB antigens through in-trans surface display provides an effective and safe vaccine approach against TB. Such non-recombinant probiotic surface display strategy involves the fusion of candidate proteins with cell wall binding domain such as LysM, which enables the fusion protein to anchor the L. plantarum cell wall externally, without the need for vector genetic modification. This approach requires sufficient production of these recombinant fusion proteins in cell factory such as Escherichia coli which has been shown to be effective in heterologous protein production for decades. However, overexpression in E. coli expression system resulted in limited amount of soluble heterologous TB-LysM fusion protein, since most of it are accumulated as insoluble aggregates in inclusion bodies (IBs). Conventional methods of denaturation and renaturation for solubilizing IBs are costly, time-consuming and tedious. Thus, in this study, an alternative method for TB antigen-LysM protein solubilization from IBs based on the use of non-denaturating reagent N-lauroylsarcosine (NLS) was investigated. RESULTS: Expression of TB antigen-LysM fusion genes was conducted in Escherichia coli, but this resulted in IBs deposition in contrast to the expression of TB antigens only. This suggested that LysM fusion significantly altered solubility of the TB antigens produced in E. coli. The non-denaturing NLS technique was used and optimized to successfully solubilize and purify ~ 55% of the recombinant cell wall-anchoring TB antigen from the IBs. Functionality of the recovered protein was analyzed via immunofluorescence microscopy and whole cell ELISA which showed successful and stable cell wall binding to L. plantarum (up to 5 days). CONCLUSION: The presented NLS purification strategy enables an efficient and rapid method for obtaining higher yields of soluble cell wall-anchoring Mycobacterium tuberculosis antigens-LysM fusion proteins from IBs in E. coli.


Assuntos
Antígenos de Bactérias/metabolismo , Parede Celular/metabolismo , Corpos de Inclusão/metabolismo , Proteínas Recombinantes de Fusão/metabolismo , Proteínas Recombinantes/metabolismo , Antígenos de Bactérias/genética , Escherichia coli/metabolismo , Lactobacillus plantarum/metabolismo , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/metabolismo , Proteínas Recombinantes de Fusão/genética , Vacinas contra a Tuberculose/genética , Vacinas contra a Tuberculose/metabolismo
10.
J Recept Signal Transduct Res ; 39(3): 276-282, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31509041

RESUMO

Acute myeloid leukemia (AML) constitutively express growth factors and cytokines for survival. Chemotherapy alters these signals to induce cell death. However, drug resistance in AML remains a major hindrance to successful treatment and early warning is unavailable. Modulation of signaling pathways during chemotherapy may provide a window to detect response and predict treatment outcome. Blood samples collected from AML patients before and at day-3 of induction therapy were compared for changes in expression of CD117, CD34, pro-inflammatory cytokines and mediators of Akt and MAPK pathways, using multi-color flow cytometry. Nine patients were diagnosed as drug-resistant and seven sensitive to chemotherapy. Twelve were paired. Average percentages of CD34 (66.8 ± 11.7% vs. 26.2 ± 5.8%, p = 0.033) and pBAD (66.9 ± 8.2% vs. 28.9 ± 8.2%, p = 0.016) were significantly increased in chemo-resistant (N = 9) compared to chemo-sensitive (N = 5) samples. Percentages of CD34 were strongly correlated with pBAD (R = 0.785; p = 0.001; N = 14) and pFKHR (R = 0.755; p = 0.002; N = 14) at day-3 induction. Chemo-sensitive cases expressed significantly higher percentages of IL-18Rα (71.9 ± 9.6% vs. 29.8 ± 5.8%, p = 0.016). Though not significantly different in the outcome, IL-1ß was strongly associated with activated Akt-S473, IL-6 with phosphorylated JNK and FKHR while TNF-α appeared to trigger Bim, in treated samples. These preliminary results suggested AML cells resistant to chemotherapy increased expression of CD34 and may signal through pBAD while cells sensitive to chemotherapy-induced IL18Rα expression. These were observed early during induction therapy. Identifying CD34 is interesting as it is a convenient marker to monitor drug-resistance in AML patients. Inhibition of CD34 and pBAD signaling may be important in treating drug-resistant AML.


Assuntos
Antígenos CD34/metabolismo , Antineoplásicos/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/metabolismo , Transdução de Sinais , Proteína de Morte Celular Associada a bcl/metabolismo , Adulto , Antineoplásicos/farmacologia , Citocinas/metabolismo , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Feminino , Fluorescência , Humanos , Masculino , Pessoa de Meia-Idade , Fosforilação/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
11.
Eur J Clin Microbiol Infect Dis ; 38(12): 2349-2353, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31529307

RESUMO

Clinical manifestations of leptospirosis range from mild, common cold-like illness, to a life-threatening condition. The host immune response has been hypothesized to play a major role in leptospirosis outcome. Increased levels of inflammatory mediators, such as cytokines, may promote tissue damage that lead to increased disease severity. The question is whether cytokines levels may predict the outcome of leptospirosis and guide patient management. This study aimed to assess the association between Th1-, Th2-, and Th17-related cytokines with the clinical outcome of patients with leptospirosis. Different cytokine levels were measured in fifty-two plasma samples of hospitalized patients diagnosed with leptospirosis in Malaysia (January 2016-December 2017). Patients were divided into two separate categories: survived (n = 40) and fatal outcome (n = 12). Nineteen plasma samples from healthy individuals were obtained as controls. Cytokine quantification was performed using Simple Plex™ assays from ProteinSimple (San Jose, CA, USA). Measurements were done in triplicate and statistical analysis was performed using GraphPad software and SPSS v20. IL-6 (p = 0.033), IL-17A (p = 0.022), and IL-22 (p = 0.046) were significantly elevated in fatal cases. IL-17A concentration (OR 1.115; 95% CI 1.010-1.231) appeared to be an independent predictor of fatality of leptospirosis. Significantly higher levels of TNF-α (p ≤ 0.0001), IL-6 (p ≤ 0.0001), IL-10 (p ≤ 0.0001), IL-12 (p ≤ 0.0001), IL17A (p ≤ 0.0001), and IL-18 (p ≤ 0.0001) were observed among leptospirosis patients in comparison with healthy controls. Our study shows that certain cytokine levels may serve as possible prognostic biomarkers in leptospirosis patients.


Assuntos
Citocinas/sangue , Leptospirose/sangue , Leptospirose/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Humanos , Interleucina-17/sangue , Interleucina-6/sangue , Interleucinas/sangue , Leptospirose/patologia , Leptospirose/fisiopatologia , Malásia/epidemiologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Adulto Jovem , Interleucina 22
12.
BMC Biotechnol ; 18(1): 63, 2018 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-30309359

RESUMO

BACKGROUND: Tuberculosis is one of the most common and deadliest infectious diseases worldwide affecting almost a third of the world's population. Although this disease is being prevented and controlled by the Bacille Calmette Guérin (BCG) vaccine, the protective efficacy is highly variable and substandard (0-80%) in adults. Therefore, novel and effective tuberculosis vaccine that can overcome the limitations from BCG vaccine need to be developed. RESULTS: A novel approach of utilizing an in-trans protein surface display system of Lactobacillus plantarum carrying and displaying combination of Mycobacterium tuberculosis subunit epitope antigens (Ag85B, CFP-10, ESAT-6, Rv0475 and Rv2031c) fused with LysM anchor motif designated as ACERL was constructed, cloned and expressed in Esherichia coli Rossetta expression host. Subsequently the binding capability of ACERL to the cell wall of L. plantarum was examined via the immunofluorescence microscopy and whole cell ELISA where successful attachment and consistent stability of cell wall binding up to 4 days was determined. The immunization of the developed vaccine of L. plantarum surface displaying ACERL (Lp ACERL) via the oral route was studied in mice for its immunogenicity effects. Lp ACERL immunization was able to invoke significant immune responses that favor the Th1 type cytokine response of IFN-γ, IL-12 and IL-2 as indicated by the outcome from the cytokine profiling of spleen, lung, gastrointestinal tract (GIT), and the re-stimulation of the splenocytes from the immunized mice. Co-administration of an adjuvant consisting of Lactococcus lactis secreting mouse IL-12 (LcIL-12) with Lp ACERL was also investigated. It was shown that the addition of LcIL-12 was able to further generate significant Th1 type cytokines immune responses, similar or better than that of Lp ACERL alone which can be observed from the cytokine profiling of the immunized mice's spleen, lung and GIT. CONCLUSIONS: This study represents a proof of concept in the development of L. plantarum as a carrier for a non-genetically modified organism (GMO) tuberculosis vaccine, which may be the strategy in the future for tuberculosis vaccine development.


Assuntos
Lactobacillus plantarum/genética , Vacinas contra a Tuberculose/administração & dosagem , Vacinas contra a Tuberculose/genética , Tuberculose/prevenção & controle , Aciltransferases/administração & dosagem , Aciltransferases/genética , Aciltransferases/imunologia , Administração Oral , Animais , Antígenos de Bactérias/administração & dosagem , Antígenos de Bactérias/genética , Antígenos de Bactérias/imunologia , Proteínas de Bactérias/administração & dosagem , Proteínas de Bactérias/genética , Proteínas de Bactérias/imunologia , Feminino , Expressão Gênica , Humanos , Imunização , Interleucina-2/genética , Interleucina-2/imunologia , Interleucina-4/genética , Interleucina-4/imunologia , Interleucina-6/genética , Interleucina-6/imunologia , Lactobacillus plantarum/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/imunologia , Tuberculose/genética , Tuberculose/imunologia , Tuberculose/microbiologia , Vacinas contra a Tuberculose/imunologia
13.
Asian Pac J Allergy Immunol ; 33(1): 26-32, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25840631

RESUMO

BACKGROUND: Tamm-Horsfall glycoprotein (THP) and uromodulin are the most abundant glycoproteins in non-pregnant women's/men's and pregnant women's urine, respectively. However, the bioactivities of these glycoproteins are still unclear. OBJECTIVE: To evaluate the immunomodulatory properties of THP and uromodulin on human peripheral blood mononuclear cells (PBMC) METHODS: THP and uromodulin isolated with diatomaceous earth filtration were subjected to several bioassays, such as MTS viability assay, immunophenotyping and cytokine analysis. RESULTS: MTS viability assay and immunophenotyping analysis showed that uromodulin has greater inhibitory activities in suppressing PBMC viability and the percentage of CD4⁺ T helper cells and CD8⁺ cytotoxic T cells, compared to that of THP. In cytokine analysis, THP tended to induce pro-inflammatory cytokines such as IL-1ß, TNF and Th1 cytokine IFN-γ; while uromodulin only induced IL-1ß and suppressed both Th1 cytokine IFN-γ and Th2 cytokine IL-10. CONCLUSION: These results demonstrate that uromodulin has greater immunosuppressive activities and lower inductive property in relation to activation of immune cells, which provides a more tolerant environment for the developing fetus.


Assuntos
Fatores Imunológicos/farmacologia , Linfócitos T Citotóxicos/efeitos dos fármacos , Linfócitos T Auxiliares-Indutores/efeitos dos fármacos , Uromodulina/farmacologia , Adulto , Feminino , Humanos , Fatores Imunológicos/isolamento & purificação , Fatores Imunológicos/urina , Imunofenotipagem , Interferon gama/biossíntese , Interferon gama/metabolismo , Interleucina-10/biossíntese , Interleucina-10/metabolismo , Interleucina-1beta/biossíntese , Interleucina-1beta/metabolismo , Ativação Linfocitária/efeitos dos fármacos , Masculino , Gravidez , Cultura Primária de Células , Linfócitos T Citotóxicos/citologia , Linfócitos T Citotóxicos/imunologia , Linfócitos T Citotóxicos/metabolismo , Linfócitos T Auxiliares-Indutores/citologia , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Auxiliares-Indutores/metabolismo , Equilíbrio Th1-Th2/efeitos dos fármacos , Fator de Necrose Tumoral alfa/biossíntese , Fator de Necrose Tumoral alfa/metabolismo , Uromodulina/isolamento & purificação , Uromodulina/urina
14.
Malays J Pathol ; 37(2): 83-90, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26277663

RESUMO

Soluble HLA (sHLA) are potential tumour markers released in order to counter immune surveillance. sHLA-class II is less known especially in acute lymphoblastic leukaemia (ALL). This study aimed to investigate soluble, surface and allelic expression of HLA Class II (sHLA-DR) in B-cell ALL patients and compare with soluble expression in normal individuals. A sandwich enzyme-linked immunosorbent assay (ELISA) was developed to measure soluble HLA-DRB1 in plasma. Flow cytometric analysis was performed to determine median fluorescence intensity in HLA-DR surface expression. HLA-DNA typing by polymerase chain reaction, sequence specific oligonucleotides, PCRSSO was performed to determine HLA-DRB1 type in ALL samples. Results showed sHLA-DRB1 (mean±SEM) was significantly increased (p=0.001) in plasma of ALL patients (0.260 ±0.057 µg/mL; n=30) compared to healthy controls (0.051 ± 0.007µg/mL; n=31) of Malay ethnicity. However, these levels did not correlate with percentage or median fluorescence intensity of HLA-DR expressed on leukemia blasts (CD19+CD34 ± CD45(lo)HLA-DR+) or in the normal B cell population (CD19+CD34- CD45(hi)HLA-DR+) of patients. No significant difference was observed in gender (male/female) or age (paediatric/adult). Only a trend in reduced sHLA was observed in patients carrying HLA-DR04. These results have to be validated with a larger number of samples.


Assuntos
Biomarcadores Tumorais/análise , Cadeias HLA-DRB1/biossíntese , Leucemia-Linfoma Linfoblástico de Células Precursoras B/imunologia , Adolescente , Adulto , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Humanos , Masculino , Reação em Cadeia da Polimerase , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patologia , Adulto Jovem
16.
Cell Biol Int ; 37(3): 250-6, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23364902

RESUMO

Mesenchymal stem cells (MSC) generated from human umbilical cord (UC-MSC) and placenta (PLC-MSC) were assessed and compared for their immunomodulatory function on T cells proliferation by analysis of the cell cycle. Mitogen stimulated or resting T cells were co-cultured in the presence or absence of MSC. T-cell proliferation was assessed by tritiated thymidine ((3) H-TdR) assay and the mechanism of inhibition was examined bycell cycle and apoptosis assay. Both UC-MSC and PLC-MSC profoundly inhibited the proliferation of T-cell, mainly via cell-to-cell contact. MSC-mediated anti-proliferation does not lead to apoptosis,but prevented T cells from entering S phase and they therefore accumulated in the G(0) /G(1) phases. The anti-proliferative activity of MSC was related to this cell cycle arrest of T-cell. UC-MSC produced a greater inhibition than PLC-MSC in all measured parameters.


Assuntos
Proliferação de Células , Células-Tronco Mesenquimais/fisiologia , Linfócitos T/imunologia , Apoptose , Pontos de Checagem do Ciclo Celular , Células Cultivadas , Técnicas de Cocultura , Feminino , Humanos , Placenta/citologia , Gravidez , Fase de Repouso do Ciclo Celular , Linfócitos T/fisiologia , Cordão Umbilical/citologia
17.
Breast Cancer ; 30(5): 810-819, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37306933

RESUMO

BACKGROUND: Although higher survival rates of breast cancer are achieved these days, breast cancer survivors are challenged with unwanted side effects from treatment or management that affect physical, functional, and psychological well-being of an individual. This study aimed to assess psychological distress status in Malaysian breast cancer survivors and factors that affected the condition. METHODS: A cross-sectional study design was conducted on 162 breast cancer survivors from various breast cancer support groups in Malaysia. Psychological distress status was assessed based on depression and anxiety scores by applying the Malay version of Patient Health Questionnaire (PHQ-9) and General Anxiety Disorder (GAD-7). Both instruments were self-administered along with a set of questionnaires comprising demographic, medical history, quality of life, and upper extremity function assessment. Outcomes from the PHQ-9 and GAD-7 were analyzed for severity level of psychological distress, and its association with relevant variables, arm morbidity symptoms, as well as the duration of cancer survivorship. RESULTS: The univariate analysis showed that breast cancer survivors with arm morbidities after breast surgery had a higher score of depression (5.0 vs 4.0, p = 0.011) and anxiety (3.0 vs 1.0, p = 0.026) than those who did not. Besides that, receiving fewer post-rehabilitation treatments (p = 0.049) and having a family history of cancer (p = 0.022) were correlated with higher anxiety level. The level of depression and anxiety was inversely proportionate with quality of life and positively correlated with greater disability of the arm function (p < 0.05). Subsequent analysis showed that arm morbidity symptoms including difficulties in finding a t-shirt that fits and pain in the arm area after breast cancer surgery were positively associated with a higher level of psychological distress. CONCLUSION: Our study demonstrated the association between psychological distress with arm morbidities in breast cancer survivors. Given that arm morbidities can affect not only physical, but psychological well-being, continuous or serial assessment on both aspects during cancer treatment may effectively help to address mental health issue experienced by this cancer population.


Assuntos
Neoplasias da Mama , Sobreviventes de Câncer , Humanos , Feminino , Neoplasias da Mama/psicologia , Sobreviventes de Câncer/psicologia , Questionário de Saúde do Paciente , Qualidade de Vida/psicologia , Braço , Estudos Transversais , Depressão/diagnóstico , Depressão/epidemiologia , Depressão/etiologia , Ansiedade/diagnóstico , Ansiedade/epidemiologia , Ansiedade/etiologia , Inquéritos e Questionários , Morbidade , Estresse Psicológico/diagnóstico , Estresse Psicológico/epidemiologia , Estresse Psicológico/etiologia
18.
Ann Saudi Med ; 43(6): 386-393, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38071440

RESUMO

BACKGROUND: The prevalence of inflammatory bowel diseases (IBD), Crohn's (C) and ulcerative colitis (UC) has increased in Saudi Arabia during the past decade. Even though medical treatment is first-line therapy, most patients require surgery during the course of the disease. Stoma creation complications in IBD are underreported in the literature of the Middle East and especially in Saudi Arabia. OBJECTIVES: Report the postoperative, stoma and peristomal complications following stoma creation in (C) versus UC. DESIGN: Retrospective cohort study. SETTINGS: Tertiary care center. PATIENTS AND METHODS: Patients with IBD who underwent stoma creation for either UC or CD between August 2015 and July 2020 were included. The diseases were compared to assess their characteristics and association to postoperative, stoma and peristomal complications. All complications were reported over a 90-day duration from the surgery. Patients younger than 14 years of age were excluded. MAIN OUTCOME MEASURES: Postoperative complications, stoma and peristomal complications in IBD patients who underwent stoma creation. SAMPLE SIZE: 50. RESULTS: Of 50 IBD patients underwent stoma creation, 32 patients (64%) were diagnosed with CD and 18 patients (36%) with UC. Most of the procedures in both groups were laparoscopic and elective. Low BMI and serum albumin were more prevalent in the CD group. Postoperative complications were higher in the CD patients compared to the UC patients (CD 40.6% vs UC 11.1%, P=.028) with the most common complication being abdominal collection[a]. Stoma complications were comparable between the two groups (UC 16.7% vs CD 15.6%). However, peristomal complications were higher clinically in UC patients in comparison with the CD patients (UC 61.1% vs CD 37.5% P=.095) with the most common complication being skin excoriation (UC 44.4% vs CD 37.5%). CONCLUSIONS: CD has significantly higher postoperative complications compared to UC. Peristomal complications were high in both groups and had a negative impact on quality of life. Therefore, comprehensive stoma education and regular outpatient follow ups are recommended to improve the overall outcomes. LIMITATIONS: Retrospective and conducted in one academic institution with a small sample size.


Assuntos
Colite Ulcerativa , Doenças Inflamatórias Intestinais , Humanos , Estudos Retrospectivos , Arábia Saudita/epidemiologia , Qualidade de Vida , Doenças Inflamatórias Intestinais/cirurgia , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/epidemiologia , Colite Ulcerativa/cirurgia , Colite Ulcerativa/complicações , Colite Ulcerativa/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Resultado do Tratamento
19.
Cureus ; 15(12): e50972, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38259376

RESUMO

INTRODUCTION: Tear sampling is an attractive option for collecting biological samples in ophthalmology clinics, as it offers a non-invasive alternative to other invasive techniques. However, there are many tear sampling methods still in consideration. This study explores the suitability of Schirmer's test strip and microcapillary tube as reliable and satisfactory methods for tear sampling. METHODS: Tear samples were collected from eight healthy volunteers using the standard Schirmer's test strip method with or without anesthesia and microcapillary tubes. The total tear protein concentrations were analyzed via spectrophotometry and bicinchoninic acid (BCA) protein assay. The protein profile was determined by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). The optimal wetting length of Schirmer's strip and suitable buffer solutions were compared. Discomfort levels reported by participants and the ease of execution for ophthalmologists were also evaluated. RESULTS: Tear samples exhibited typical protein profiles as shown by SDS-PAGE. The mean total protein obtained from an optimum wetting length of 20 mm using Schirmer's strip without anesthesia in phosphate-buffered saline (PBS) yielded substantial quantities of protein as measured by nanophotometer (220.20 ± 67.43 µg) and the BCA protein assay (210.34 ± 59.46 µg). This method collected a significantly higher quantity of protein compared to the microcapillary tube method (p=0.004) which was much more difficult to standardize. The clinician found it harder to utilize microcapillary tubes, while participants experienced higher insecurity and less discomfort with the microcapillary tube method. PBS used during the tear protein extraction process eluted higher tear protein concentration than ammonium bicarbonate, although the difference was not statistically significant. Using anaesthesia did not ease the sampling procedure substantially and protein quantity was maintained. CONCLUSION: Good quality and quantity of protein from tear samples were extracted with the optimized procedure. Schirmer's strip test in the absence of local anesthesia provided a standard, convenient, and non-invasive method for tear collection.

20.
Cell Immunol ; 272(2): 214-9, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22078320

RESUMO

Differences in gender immune response have resulted in differences in immune protection and susceptibility to inflammatory diseases. Cultured peripheral blood mononuclear cells (PBMC) are widely used in immunomodulation studies, yet the influence of gender is usually not considered. We examined the effect of in vitro culture and phytohaemagglutinin (PHA) stimulation on PBMC lymphocyte subsets using flowcytometry. Full blood counts of whole blood showed higher levels of lymphocyte in male subjects. Lymphocyte subsets enumeration revealed higher NK cell counts in males and higher B cells in females. Cultured PBMC resulted in significant increases in B and total T cell percentages among females and NK cells among males. PHA stimulated significantly increased percentages of NK and total T cells in males and total activated T cells (CD69+) in females. Our results showed significant gender differences in lymphocyte subsets in cultured conditions. This may affect experimental outcome.


Assuntos
Leucócitos Mononucleares/imunologia , Subpopulações de Linfócitos/imunologia , Adulto , Linfócitos B/imunologia , Contagem de Células Sanguíneas/métodos , Complexo CD3/imunologia , Células Cultivadas , Feminino , Humanos , Células Matadoras Naturais/imunologia , Ativação Linfocitária/imunologia , Masculino , Fito-Hemaglutininas/imunologia , Fatores Sexuais , Linfócitos T/imunologia , Adulto Jovem
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