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1.
Braz. j. biol ; 84: e250575, 2024. tab, graf
Article in English | LILACS, VETINDEX | ID: biblio-1350309

ABSTRACT

Abstract Cancer is a fatal malignancy and its increasing worldwide prevalence demands the discovery of more sensitive and reliable molecular biomarkers. To investigate the GINS1 expression level and its prognostic value in distinct human cancers using a series of multi-layered in silico approach may help to establish it as a potential shared diagnostic and prognostic biomarker of different cancer subtypes. The GINS1 mRNA, protein expression, and promoter methylation were analyzed using UALCAN and Human Protein Atlas (HPA), while mRNA expression was further validated via GENT2. The potential prognostic values of GINS1 were evaluated through KM plotter. Then, cBioPortal was utilized to examine the GINS1-related genetic mutations and copy number variations (CNVs), while pathway enrichment analysis was performed using DAVID. Moreover, a correlational analysis between GINS1 expression and CD8+ T immune cells and a the construction of gene-drug interaction network was performed using TIMER, CDT, and Cytoscape. The GINS1 was found down-regulated in a single subtypes of human cancer while commonly up-regulated in 23 different other subtypes. The up-regulation of GINS1 was significantly correlated with the poor overall survival (OS) of Liver Hepatocellular Carcinoma (LIHC), Lung Adenocarcinoma (LUAD), and Kidney renal clear cell carcinoma (KIRC). The GINS1 was also found up-regulated in LIHC, LUAD, and KIRC patients of different clinicopathological features. Pathways enrichment analysis revealed the involvement of GINS1 in two diverse pathways, while few interesting correlations were also documented between GINS1 expression and its promoter methylation level, CD8+ T immune cells level, and CNVs. Moreover, we also predicted few drugs that could be used in the treatment of LIHC, LUAD, and KIRC by regulating the GINS1 expression. The expression profiling of GINS1 in the current study has suggested it a novel shared diagnostic and prognostic biomarker of LIHC, LUAD, and KIRC.


Resumo O câncer é uma doença maligna fatal e sua crescente prevalência mundial exige a descoberta de biomarcadores moleculares mais sensíveis e confiáveis. Investigar o nível de expressão de GINS1 e seu valor prognóstico em cânceres humanos distintos, usando uma série de abordagens in silico em várias camadas, pode ajudar a estabelecê-lo como um potencial biomarcador de diagnóstico e prognóstico compartilhado de diferentes subtipos de câncer. O mRNA de GINS1, a expressão da proteína e a metilação do promotor foram analisados ​​usando UALCAN e Human Protein Atlas (HPA), enquanto a expressão de mRNA foi posteriormente validada via GENT2. Os valores prognósticos potenciais de GINS1 foram avaliados por meio do plotter KM. Em seguida, o cBioPortal foi utilizado para examinar as mutações genéticas relacionadas ao GINS1 e as variações do número de cópias (CNVs), enquanto a análise de enriquecimento da via foi realizada usando DAVID. Além disso, uma análise correlacional entre a expressão de GINS1 e células imunes T CD8 + e a construção de uma rede de interação gene-droga foi realizada usando TIMER, CDT e Cytoscape. O GINS1 foi encontrado regulado negativamente em um único subtipo de câncer humano, enquanto comumente regulado positivamente em 23 outros subtipos diferentes. A regulação positiva de GINS1 foi significativamente correlacionada com a sobrevida global pobre (OS) de Carcinoma Hepatocelular de Fígado (LIHC), Adenocarcinoma de Pulmão (LUAD) e Carcinoma de Células Claras Renais de Rim (KIRC). O GINS1 também foi encontrado regulado positivamente em pacientes LIHC, LUAD e KIRC de diferentes características clínico-patológicas. A análise de enriquecimento de vias revelou o envolvimento de GINS1 em duas vias diversas, enquanto poucas correlações interessantes também foram documentadas entre a expressão de GINS1 e seu nível de metilação do promotor, nível de células imunes T CD8 + e CNVs. Além disso, também previmos poucos medicamentos que poderiam ser usados ​​no tratamento de LIHC, LUAD e KIRC, regulando a expressão de GINS1. O perfil de expressão de GINS1 no estudo atual sugeriu que é um novo biomarcador de diagnóstico e prognóstico compartilhado de LIHC, LUAD e KIRC.


Subject(s)
Humans , Carcinoma, Renal Cell/genetics , Kidney Neoplasms/genetics , Liver Neoplasms , Prognosis , Biomarkers, Tumor/genetics , Gene Expression Regulation, Neoplastic , Up-Regulation , DNA-Binding Proteins , DNA Copy Number Variations
2.
Rev. med. (São Paulo) ; 101(5): e-181721, set-out. 2022.
Article in English, Portuguese | LILACS-Express | LILACS | ID: biblio-1395427

ABSTRACT

Introduction: Acute Lymphoblastic Leukemia (ALL) is the most prevalent malignancy in children; however, when the neoplasm becomes refractory/relapses (R/R) the cure possibilities are practically null. Objectives: To analyze the Anti-CD19 Chimeric Antigen Receptors (CAR) T-Cells immunotherapy efficacy in the treatment of R/R ALL, providing evidence about the efficacy and safety of the therapy for the analyzed group. Methods: The study consisted of a systematic review and meta-analysis based on the analysis of indexed articles. The searches were carried out with the terms: "acute lymphoblastic leukemia", "CAR T", and "CD19-specific chimeric antigen receptor". Results: Only 18 of the 94 articles obtained initially met the inclusion criteria and were selected for review, totaling 637 patients. Thus, it was observed in the responses that approximately 81% of the patients achieved a Complete Response; 7% did not respond; the neoplasm relapsed in 17% of the cases; and 6.1% of the patients died. The main side effects found were Cytokine Release Syndrome (CRS), Severe Cytokine Release Syndrome, and Neurotoxicity, present in 36.3%, 29%, and 24% of patients, respectively. Conclusion: Anti-CD19 CAR T-Cells immunotherapy is an effective therapy, capable of producing high rates of complete remission in R/R ALL treatment. [au]


Introdução: A Leucemia Linfoblástica Aguda (LLA) é a neoplasia maligna mais prevalente em crianças; entretanto, quando se torna refratária/recidivante (R/R) as possibilidades de cura são praticamente nulas. Objetivos: Analisar a eficácia da imunoterapia de Receptores de Antígenos Quiméricos anti-CD19 no tratamento da LLA R/R, fornecendo evidências sobre a efetividade e segurança da terapia para o grupo analisado. Métodos: O estudo consistiu em uma revisão sistemática e metanálise baseada em artigos indexados. As pesquisas foram realizadas com os termos: "acute lymphoblastic leukemia", "CAR T", and "CD19-specific chimeric antigen receptor". Resultados: Dos 94 artigos obtidos, apenas 18 atenderam inicialmente aos critérios de inclusão e foram selecionados para revisão, totalizando 637 pacientes. Assim, observou-se nas respostas que aproximadamente 81% dos pacientes obtiveram resposta completa; 7% não responderam; a neoplasia recidivou em 17% dos casos; e 6,1% dos pacientes morreram. Os principais efeitos colaterais encontrados foram síndrome de liberação de citocinas, síndrome de liberação grave de citocinas e neurotoxicidade, presentes em 36,3%, 29% e 24% dos pacientes, respectivamente. Conclusão: A imunoterapia com células CAR T anti-CD19 é uma terapia eficaz, sendo capaz de produzir altas taxas de remissão completa no tratamento de LLA R / R. [au]

3.
Rev. cientif. cienc. med ; 25(1): 58-62, sept. 2022.
Article in Spanish | LILACS | ID: biblio-1399912

ABSTRACT

El sarcoma de ewing es un tumor maligno de rápido crecimiento, con prevalencia de 1-5 casos por cada 1.000.000 habitantes, su forma extraesquelética en la cavidad sinonasal o senos paranasales es inusual. Objetivo: describir la localización atípica de esta neoplasia y la importancia de lograr un diagnóstico oportuno. Paciente femenina, con una masa en la cavidad nasal derecha de dos meses de evolución, cefalea y epistaxis. Con asimetría en región orbitaria derecha y deformidad del tabique nasal, senos paranasales con sintomas de obstrucción. La tomografía reveló una masa que invade senos paranasales. La biopsia mostró un sarcoma de Ewing. Se confirmó con CD99. La paciente recibió quimioterapia y plan de resección quirúrgica, pero falleció. El diagnóstico y tratamiento oportuno del sarcoma de ewing en cavidad sinonasal debe apoyarse con examenes tomográficos, histopatológicos, inmunohistoquímicos y de ser posible citogenéticos para llegar al diagnóstico definitivo en etapas tempranas del tumor


Ewing's sarcoma is a rapidly growing malignant tumor, with a prevalence of 1-5 cases per 1,000,000 inhabitants, its extraskeletal shape in the sinonasal cavity or paranasal sinuses is unusual. Objective: to describe the atypical location of this neoplasm and the importance of achieving a timely diagnosis. Female patient, with a mass in the right nasal cavity of two months of evolution, headache and epistaxis. With asymmetry in the right orbital region and deformity of the nasal septum, paranasal sinuses with symptoms of obstruction. Tomography revealed a mass that invades the paranasal sinuses. The biopsy showed Ewing's sarcoma. It was confirmed with CD99. The patient received chemotherapy and a surgical resection plan, however she died. The timely diagnosis and treatment of Ewing's sarcoma in the sinonasal cavity should not be based solely on clinical evaluation, it requires a tomographic, histopathological, immunohistochemical and, if possible, cytogenetic examination to reach a definitive diagnosis in the early stages of the tumor.


Subject(s)
Female , Child , Epistaxis , Biopsy , Tomography , Drug Therapy
4.
Rev. bras. cir. cardiovasc ; 37(3): 350-355, May-June 2022. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1376543

ABSTRACT

Abstract Objective: To investigate the expression level and significance of T cell immunoglobulin and mucin-domain containing molecules-3 (Tim-3) and interleukin-7 (IL-7) in CD4+ T lymphocytes in peripheral blood of patients with coronary heart disease (CHD). Methods: 75 patients with CHD treated at our hospital were selected and classified as mild group (25 cases), moderate group (25 cases) and severe group (25 cases), according to the severity of illness. Twenty-five healthy volunteers who underwent a physical examination at our hospital during the same period were selected as the control group. The expression level of Tim-3 in CD4+ T lymphocytes in peripheral blood of patients in four groups was detected by flow cytometry and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). The expression level of IL-7 in peripheral blood serum was measured by enzyme-linked immunosorbent assay (ELISA). Correlation analyses of Tim-3 and IL-7, Tim-3 and disease severity and IL-7 and disease severity were performed, respectively. Results: Flow cytometry and qRT-PCR demonstrated that the expression of Tim-3 in CD4+ T lymphocytes in peripheral blood of patients with CHD increased with the aggravation of the disease. ELISA showed that the tendency of IL-7 expression in peripheral blood serum was consistent with the expression of Tim-3, and the expression of Tim-3 had a positive correlation with IL-7. The expression levels of both Tim-3 and IL-7 were positively correlated with the Gensini score. Conclusion: The expression of Tim-3 and IL-7 in peripheral blood of patients with CHD was upregulated and increased with the aggravation of CHD.

5.
Article in English | LILACS-Express | LILACS | ID: biblio-1385896

ABSTRACT

ABSTRACT: The most widely used method to classify prognostic factors in cancers today is TNM. However, Oral Squamous Cell Carcinoma (OSCC) often demonstrates different behaviors in relation to aggressiveness and therapeutic response at the same TNM stage. So, in such cases biomarkers can be used to identify the biological diversity of these tumors more reliably, leading to better therapeutic strategies and disease management. The presence of inflammatory immune cells in the tumor microenvironment can have pro or antitumor effects and the investigation of the expression of inflammatory markers in OSSC can be usefulto design immunotherapeutic interventions. The Transforming Growth Factor alpha is a potent stimulator of cell migration that acts on cell proliferation, invasion and metastasis of cancer, as well as immune suppression and angiogenesis. Inflammatory cytokines, such as Interferon-gamma, mediate macrophage differentiation. Macrophages are an important component of the OSCC microenvironment. The greater amount of tumor-associated macrophages, especially the M2 phenotype, may be associated with a more aggressive biological behavior of the OSCC and, consequently, with reduced survival.


RESUMEN: El método más utilizado para clasificar los factores de pronóstico en los cánceres en la actualidad es TNM. Sin embargo, el carcinoma oral de células escamosas (COCE) a menudo muestra diferentes comportamientos en relación con la agresividad y la respuesta terapéutica en la misma etapa TNM. Entonces, en tales casos, los biomarcadores pueden usarse para identificar la diversidad biológica de estos tumores de manera más confiable, lo que lleva a mejores estrategias terapéuticas y manejo de la enfermedad. La presencia de células inmunes inflamatorias en el microambiente tumoral puede tener efectos pro o antitumorales y la investigación de la expresión de marcadores inflamatorios en COCE puede ser útil para diseñar intervenciones inmunoterapéuticas. El factor de crecimiento transformante α es un potente estimulador de la migración celular que actúa sobre la proliferación celular, la invasión y metástasis del cáncer, así como la inmunosupresión y la angiogénesis. Las citocinas inflamatorias, como el IFN-γ, median en la diferenciación de macrófagos. Los macrófagos son un componente importante del microambiente COCE. La mayor cantidad de macrófagos asociados a tumores, especialmente el fenotipo M2, puede estar asociada a un comportamiento biológico más agresivo del COCE y, en consecuencia, a una menor supervivencia.

6.
Hematol., Transfus. Cell Ther. (Impr.) ; 44(2): 143-150, Apr.-June 2022. tab, graf
Article in English | LILACS | ID: biblio-1385039

ABSTRACT

Abstract Introduction Flow cytometric immunophenotyping (FCI) plays a major role in diagnosing hematologic malignancies. In patients diagnosed with precursor B-lineage acute lymphoblastic leukemia (B-ALL), expression of certain non-lineage/cross lineage antigens is of prognostic and cytogenetic relevance. There is a paucity of studies that have comprehensively analyzed the clinical and laboratory profiles of B-ALL patients showing aberrant T/natural killer (NK) cell antigen expression. Materials and methods This is a prospective study where 152 consecutive B-ALL patients were analyzed for aberrant expression of T/NK cell antigens (CD1a, CD5, CD4, CD7, CD8 and CD56) by FCI. The clinical and laboratory profile of these T/NK-cell antigen-expressing B-ALL patients was statistically analyzed against conventional B-ALL patients. Results In our B-ALL cohort, CD5, CD7 and CD56 expression were observed in one, six and nine patients, respectively. CD56-expressing B-ALL patients were predominantly children (89%) and presented as standard clinical risk (p = 0.010) disease with frequent ETV6-RUNX1 fusion (p = 0.021) positivity. On the contrary, CD7-expressing B-ALL patients were adolescent-young adult/adult-age skewed (83%) and had an adverse cytogenetic profile (p = 0.001), especially for the frequent presence of BCR-ABL1 fusion (p = 0.004) and KMT2A rearrangement (p = 0.045). CD7-expressing B-ALL patients had inferior event-free survival (p = 0.040) than their CD56-expressing counterparts, but there was no significant difference in the overall survival (p = 0.317). Conclusion In comparison to conventional B-ALL patients, there are significant differences in the age, cytogenetic profile and event-free survival of T/NK-cell antigen-expressing B-ALL patients.


Subject(s)
Humans , Male , Female , Infant , Child, Preschool , Child , Adolescent , Adult , Middle Aged , Young Adult , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma , Flow Cytometry , Immunophenotyping , Antigens, CD7 , CD56 Antigen
7.
Hematol., Transfus. Cell Ther. (Impr.) ; 44(1): 49-55, Jan.-Mar. 2022. tab, graf
Article in English | LILACS | ID: biblio-1364889

ABSTRACT

Abstract Background This study aims to validate the single-platform method for enumeration of CD34+ cells, by comparing the performance of two different commercial kits, as well as to evaluate the efficiency of the AccuriTM C6 cytometer in providing direct counts of absolute cell numbers. Method We evaluated 20 samples from umbilical cord blood (UCB), comparing the two different methodologies for enumeration of CD34+ cells: single and dual-platform. For the assessment of the single-platform, Procount and SCE kits were used, both of which use fluorescent beads as a counting reference to obtain absolute CD34+ cells numbers. Moreover, after the acquisition of samples in flow cytometer AccuriTM C6, following the protocol established for each kit, the number of CD34+ cells was recalculated, considering the cell count provided by the AccuriTM C6. Main Results In our analysis, the results showed a strong correlation between the number of CD34+ cells/μL (r2 = 0.77) when comparing the SCE kit and the current dual-platform method. On the other hand, the comparison between Procount kit and dual-platform results showed a moderate correlation for the number of CD34+/μL cells (r2 = 0.64). Conclusion Our results showed that the AccuriTM C6 flow cytometer can be used safely, applying both the dual and single platform analysis strategy. Considering the ISHAGE protocol-based single-platform approach, as the most appropriate methodology for CD34+ cells enumeration, our results demonstrated that the SCE kit has great potential for national standardization of UCB samples analysis methodology.


Subject(s)
Hematopoietic Stem Cells , Antigens, CD34 , Fetal Blood , Transplantation, Homologous , Guidelines as Topic , Flow Cytometry
8.
J. appl. oral sci ; 30: e20210413, 2022. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1360532

ABSTRACT

Abstract The mechanisms that stimulate the proliferation of epithelial cells in inflammatory periapical lesions are not completely understood and the literature suggests that changes in the balance between apoptosis and immunity regulation appear to influence this process. Objective: To evaluate the expression of the epidermal growth factor (EGF), its receptor (EGFR) and of the keratinocyte growth factor (KGF), the presence of CD57+ cells, the epithelial cell proliferation index, and the expression of the Bcl-2 protein in inflammatory periapical lesions (IPL) at different stages of development. Methodology: Our sample was composed of 52 IPLs (22 periapical granulomas - PG - and 30 periapical cysts - PC), divided into three groups: PGs, small PCs, and large PCs. Specimens were processed for histopathologic and immunohistochemical analyses. Sections were evaluated according to the amount of positive staining for each antibody. Results: We found no significant differences among the groups regarding Bcl-2 (p=0.328) and Ki-67 (p>0.05) expression or the presence of CD57+ cells (p=0.748). EGF (p=0.0001) and KGF (p=0.0001) expression was more frequent in PCs than in PGs, and CD57+ cells were more frequent in IPLs with intense inflammatory infiltrates (p=0.0001). We found no significant differences in KGF (p=0.423), Bcl-2 (p=0.943), and EGF (p=0.53) expression in relation to inflammatory infiltrates or to the type of PC epithelial lining, but observed greater KGF expression (p=0.0001) in initial PCs. EGFR expression was similar among the groups (p>0.05). Conclusion: More frequent EGF and KGF expression in PCs and the greater presence of CD57+ cells in lesions with intense inflammatory infiltrates suggest that these factors influence IPL development. The greater KGF expression in initial PCs suggests its importance for the initial stages of PC formation.

9.
Article in English | LILACS-Express | LILACS | ID: biblio-1360791

ABSTRACT

ABSTRACT The effect of antiretroviral therapy (ART) on CD4+/CD25hi/CD127low T lymphocyte changes in people living with HIV/AIDS (PLWHA) is still a matter of debate. From October 2015 to December 2019, peripheral blood from 70 cases of PLWHA were collected for the detection of CD4+/CD25hi/CD127low T lymphocytes by flow cytometry. Statistical analysis was performed to detect changes of CD4+/CD25hi/CD127low T lymphocytes in patients with different duration of ART and different treatment effects. We found that the number of CD4+/CD25hi/CD127low T lymphocytes in ART-naive PLWHA were lower than those in healthy volunteers (10.3±٦.٠ cells/uL vs 31.7±8.0 cells/uL, P < 0.05). CD4+/CD25hi/CD127low T lymphocyte counts increased to 17.8±٤.٠ cells/uL 6 months post-ART and 25.0±١١.٩ cells/uL 9 months post-ART, respectively (P < 0.05). There was no significant difference in CD4+/CD25hi/CD127low T lymphocyte counts between PLWHA who reached a complete immune reconstruction after ART and healthy volunteers. The growth of CD4+/CD25hi/CD127low T lymphocyte counts in patients who had baseline CD4 > 200 cells/uL was greater than those who had baseline CD4 ≤ 200 cells/uL (12.6±٤.٦ cells/uL vs 5.6±٥.٠ cells/uL, P = 0.027). CD4+/CD25hi/CD127low T lymphocyte counts were positively correlated with CD4+ T lymphocyte counts (r = 0.923, P < 0.001) and CD4+/CD8+ ratio (r = 0.741, P < 0.001), but were negatively correlated with HIV-VL (r = −0.648, P = 0.000). In conclusion, the results of the present study showed that changes in CD4+/CD25hi/CD127low T lymphocyte counts can be used to assess the effect of ART in PLWHA.

10.
Bull. méd. Owendo (En ligne) ; 20(51): 58-63, 2022. tables
Article in French | AIM | ID: biblio-1378389

ABSTRACT

Objectif : Décrire les caractéristiques cliniques de la dégénérescence maculaire (DM) chez les personnes vivant avec le VIH (PVVIH).Patients et méthodes : Il s'agissait d'une étude observationnelle menée dans le service d'infectiologie du CHU de Libreville. Il était inclus les adultes âgés de plus de 17 ans, vivant avec le VIH (PVVIH) type 1 et ayant le même protocole thérapeutique antirétroviral. Les paramètres recueillis étaient l'âge, le sexe, le taux de CD4, l'ancienneté de l'infection au VIH, le délai de mise sous traitement antirétroviral et les lésions rétiniennes en rapport avec la DM. Les paramètres des PVVIH sans DM (DM-) étaient comparés à ceux avec DM (DM+) (p < 0,05). Résultats : L'enquête avait concerné 772 personnes vivant avec le VIH (PVVIH) dont 30 avaient présenté une DM+, soit une fréquence de 4%. La moyenne d'âge des DM+ était de 50,3 ± 12,8 ans et celle des DM- de 44,9 ± 10,8 ans (0,0083).Le sex-ratio était de 0,3 chez les DM+ et de 0,24 chez les DM- (p = 0,5950). Parmi les DM+, 28 avaient une forme intermédiaire et 2 une forme tardive. Il n'existait pas de différence significative entre l'ancienneté de l'infection à VIH (p = 0,1599), le taux de CD4 (p = 0,8666) et le délai de mise sous traitement antirétroviral (p = 0,9040) entre les deux groupes (DM+, DM- ).Conclusion : Ce travail permet de constater que la dégénérescence maculaire chez les PVVIH est fréquente et précoce,avec une prédominance de la forme intermédiaire


Objective: To describe the clinicals characteristics of macular degeneration (MD) in people living with HIV.Patients and methods: This was an observational study carried out in the infectious disease department of the University Hospital of Libreville. It was included adults over the age of 17, living with type 1 HIV (PLHIV) and having the same antiretroviral therapy protocol. The parameters collected were age, gender, CD4 count, age of HIV infection, time to antiretroviral treatment, and retinal lesions related to MD. The PLHIV were divided into two groups, those without MD (MD-) and those with MD (MD+ ) (p <0.05).Results: The survey concerned 772 people living with HIV (PLHIV), of whom 30 presented with MD+, either a frequency of 4%. The mean age of DM+ was 50.3 ± 12.8 years and that of MD- 44.9 ± 10.8 years (0.0083). The sex ratio was 0.3 in DM+ and 0.24 in DM- (p = 0.5950). Of the MD+, 28 had an intermediate form and 2 had a late form. There was no significant difference between the age of HIV infection (p = 0.1599), CD4 count (p = 0.8666) and time to antiretroviral treatment (p = 0.9040) between the two groups (MD+, MD-).Conclusion: This work has shown that macular degeneration in PLHIV is frequent and early, with a predominance of theintermediate form


Subject(s)
HIV Infections , CD4 Immunoadhesins , Gestational Age , Human Characteristics , Macular Degeneration
11.
Afr. j. lab. med. (Print) ; 11(1): 1-9, 2022. tables, figures
Article in English | AIM | ID: biblio-1379112

ABSTRACT

Background: The Northern Cape is South Africa's largest province with an HIV prevalence of 7.1% versus a 13.5% national prevalence. CD4 testing is provided at three of five National Health Laboratory Service district laboratories, each covering a 250 km precinct radius. Districts without a local service report prolonged CD4 turn-around times (TAT).Objective: This study documented the impact of a new CD4 laboratory in Tshwaragano in the remote John Taolo Gaetsewe district of the Northern Cape, South Africa.Methods: CD4 test volumes and TAT (total, pre-analytical, analytical, and post-analytical) data for the Northern Cape province were extracted for June 2018 to October 2019. The percentage of CD4 results within the stipulated 40-h TAT cut-off and the median and 75th percentiles of all TAT parameters were calculated. Pre-implementation, samples collected at Tshwaragano were referred to Kimberley or Upington, Northern Cape, South Africa.Results: Pre-implementation, 95.4% of samples at Tshwaragano were referred to Kimberley for CD4 testing (36.3% of Kimberley's test volumes). Only 7.5% of Tshwaragano's total samples were referred post-implementation. The Tshwaragano laboratory's CD4 median total TAT decreased from 24.7 h pre-implementation to 12 h post-implementation (p = 0.003), with >95.0% of results reported within 40 h. The Kimberley laboratory workload decreased by 29.0%, and testing time significantly decreased from 10 h to 4.3 h.Conclusion: The new Tshwaragano CD4 service significantly decreased local TAT. Upgrading existing community laboratories to include CD4 testing can alleviate provincial service load and improve local access, TAT and efficiency in the centralised reference laboratory


Subject(s)
Humans , Male , Female , CD4 Antigens , HIV , Allergy and Immunology , Exercise Test , Hospitals, District , Laboratories , Operations Research
12.
Afr. health sci. (Online) ; 22(2): 1-11, 2022. figures, tables
Article in English | AIM | ID: biblio-1400230

ABSTRACT

Background: Moringa oleifera Lam. is known to be of high nutritional and medicinal importance and has been demonstrated to possess a variety of biological activities. Objective: This study investigated the beneficial role of M. oleifera (moringa) supplementation in HIV positive subjects receiving antiretroviral drugs. Methods: Adult HIV positive individuals (104) attending the medical outpatient clinic in a tertiary health institution in Nigeria receiving highly active anti-retroviral therapies (HAARTs) were recruited in a randomized fashion for the study. Half of the subjects received moringa supplement (20 mg daily) additionally, while the others received only HAART and represented the control group. All subjects were monitored for 3 months during which their immunological status (CD4 counts and TNF-α), and hematological abnormalities at pre (baseline) and post study periods were determined. Results: Baseline levels of CD4 increased while TNF-α decreased significantly in control and moringa supplemented groups (p < 0.01). However, the post study CD4 values in the moringa group were higher and TNF-α values were lower compared to the control group (p < 0.01). In addition, baseline hematological abnormalities (anemia, thrombocytopenia, leucopenia, lymphopenia, and neutropenia) were improved but most significantly in the moringa supplemented subjects. Conclusion: The results suggest that moringa has immune-beneficial properties and improved hematological abnormalities in HIV positive individuals receiving antiretroviral therapy.


Subject(s)
Humans , Male , Female , Pharmaceutical Preparations , HIV Infections , CD4 Lymphocyte Count , Dietary Supplements , Moringa oleifera , Anemia , Lymphopenia
13.
Article in Chinese | WPRIM | ID: wpr-928684

ABSTRACT

OBJECTIVE@#To investigate the expressions of CD33 and CD13 in newly diagnosed multiple myeloma (MM) patients and its relationship with prognosis.@*METHODS@#It was retrospectively observed that the expression of CD33 and CD13 in 121 MM patients who were newly diagnosed from January 2014 to January 2020, and the relationship between the expressions of CD33 and CD13 and patients prognosis was analyzed.@*RESULTS@#Among the 121 newly diagnosed MM patients, there were 30 patients (24.8%) in the CD33+ group and 12 patients (9.9%) in the CD13+ group. Kaplan-Meier analysis showed that, compared with the CD33- group, the progression-free survival (PFS) time and overall survival (OS) time were significantly shortened in MM patients in CD33+ group (PFS 17.5 vs 23 months, P=0.000; OS 18.5 vs 25 months, P=0.000); and the PFS time and OS time of MM patients in the CD13+ group were also significantly shortened than those in CD13- group (PFS 21 vs 22 months, P=0.012; OS 25 vs 26 months, P=0.006). Cox regression analysis showed that CD33 and CD13 were independent adverse prognostic factors in MM patients (CD33: P=0.000;CD13: P=0.003).@*CONCLUSION@#CD33 and CD13 are prognostic risk factors in patients with MM.


Subject(s)
CD13 Antigens , Cell Count , Humans , Kaplan-Meier Estimate , Multiple Myeloma , Prognosis , Retrospective Studies , Sialic Acid Binding Ig-like Lectin 3
14.
Article in Chinese | WPRIM | ID: wpr-928673

ABSTRACT

OBJECTIVE@#To analyze the expression and clinical characteristics of CD68 in bone marrow and peripheral blood of patients with acute myeloid leukemia (AML).@*METHODS@#The expression of CD68 in bone marrow blast cells was detected by four-color flow cytometry in 50 newly diagnosed AML patients and 23 controls. The expression of CD68 in peripheral blood of 85 newly diagnosed AML patients, 29 remission AML patients and 24 controls was detected by ELISA. The correlation between the expression rate of non-M3 AML bone marrow CD68, peripheral blood CD68 concentration and white blood cell count and other clinical data was compared respectively.@*RESULTS@#The median CD68 expression rate in myeloid leukemia cells of non-M3 AML patients was 19.7%, significantly higher than control (0.2%) (P<0.001). The median concentration of non-M3 CD68 in peripheral blood was 67.97 pg/ml, significantly higher than in control (29.94 pg/ml)(P<0.01). There was no statistically significant difference in the plasma CD68 concentration of the peripheral blood between the newly diagnosed (45.72 pg/ml) and the remission stage (55.12 pg/ml) of non-M3 AML patients by paired analysis (P>0.05). The results showed that the higher the expression rate of CD68 in bone marrow, the higher the count of white blood cells in peripheral blood, and the lower the count of hemoglobin and platelet in peripheral blood. The higher the plasma concentration of CD68 in peripheral blood, the higher the white blood cell count and the lower the complete remission rate.@*CONCLUSION@#The expression of CD68 both in bone marrow and peripheral blood of patients with non-M3 AML is higher than that of control group. Patients with high expression of CD68 show a low rate of complete remission, suggesting that the expression level of CD68 is correlated with treatment response.


Subject(s)
Bone Marrow , Flow Cytometry , Humans , Leukemia, Myeloid, Acute , Leukocytes , Prognosis , Remission Induction
15.
Article in Chinese | WPRIM | ID: wpr-928665

ABSTRACT

OBJECTIVE@#To investigate the effect of monoammonium glycyrrhizinate on the stem cell-like characteristics, oxidative stress and mitochondrial function of acute promyelocytic leukemia cells NB4.@*METHODS@#CCK-8 method was used to detect the viability of acute promyelocytic leukemia cells NB4, and the appropriate dose was screened; Cloning method was used to detect the proliferation rate of NB4 cell; Western blot was used to detect the expression of cell cycle-related protein; flow cytometry was used to detect cell apoptosis and sort NB4 stem cells positive (CD133+); Stem cell markers (Oct4, ABCG2, Dclk1) were detected by RT-PCR; ROS was detected by fluorescence; The kit was used to detect the level of oxidative stress markers (MDA); The flow cytometry was used to detect the change of mitochondrial membrane potential; Western blot was used to detect the expression of mitochondrial damage index-related proteins (Bax/BCL-2).@*RESULTS@#Compared with the control group, if the concentration of MAG was less than 5 μmol/L, the cell NB4 viability showed no significant difference; if the concentration was higher than 5 μmol/L, the inhibitory effect on the growth of cell NB4 increased and showed significant difference (P<0.05), according to the results of CCK-8 experiment, four groups were set based on the concentration of MAG 0 μmol/L, MAG 5 μmol/L, MAG 10 μmol/L, and MAG 20 μmol/L; compared with the control group (MAG 0 μmol/L), the cells in MAG 5 μmol/L group showed no significant difference, while the proliferation rate, cyclin expression, mitochondrial membrane potential, stem cell CD133+ ratio, and marker mRNA level ( Oct4, ABCG2, Dclk1) of NB4 cell were significantly reduced (P<0.05); the apoptosis rate, reactive oxygen species, MDA content and Bax/BCL-2 expression of NB4 cell significantly increased (P<0.05).@*CONCLUSION@#Monoammonium glycyrrhizinate has a significant inhibitory effect on acute promyelocytic leukemia cells NB4, which may be related to the regulation of stem cell-like characteristics, oxidative stress and mitochondrial function.


Subject(s)
Apoptosis , Cell Line, Tumor , Doublecortin-Like Kinases , Humans , Intracellular Signaling Peptides and Proteins/metabolism , Leukemia, Promyelocytic, Acute , Mitochondria , Oxidative Stress , Protein Serine-Threonine Kinases , Stem Cells
16.
Chinese Journal of Biotechnology ; (12): 287-302, 2022.
Article in Chinese | WPRIM | ID: wpr-927712

ABSTRACT

As a non-essential metal, cadmium (Cd) pollution poses severe threats to plant growth, environment, and human health. Phytoextraction using nursery stocks prior to their transplantation is a potential useful approach for bioremediation of Cd contaminated soil. A greenhouse pot experiment was performed to investigate the growth, Cd accumulation, profiles of transcriptome as well as root-associated microbiomes of Photinia frase in Cd-added soil, upon inoculation of two types of arbuscular mycorrhizal fungi (AMF) Sieverdingia tortuosa and Funneliformis mosseae. Compared with the control, inoculation of F. mosseae increased Cd concentrations in root, stem and leaf by 57.2%, 44.1% and 71.1%, respectively, contributing to a total Cd content of 182 μg/plant. KEGG pathway analysis revealed that hundreds of genes involved in 'Mitogen-activated protein kinase (MAPK) signaling pathway', 'plant hormone signal transduction', 'biosynthesis of secondary metabolites' and 'glycolysis/gluconeogenesis' were enriched upon inoculation of F. mosseae. The relative abundance of Acidobacteria was increased upon inoculation of S. tortuosa, while Chloroflexi and Patescibacteria were increased upon inoculation of F. mosseae, and the abundance of Glomerales increased from 23.0% to above 70%. Correlation analysis indicated that ethylene-responsive transcription factor, alpha-aminoadipic semialdehyde synthase, isoamylase and agmatine deiminase related genes were negatively associated with the relative abundance of Glomerales operational taxonomic units (OTUs) upon inoculation of F. mosseae. In addition, plant cysteine oxidase, heat shock protein, cinnamoyl-CoA reductase and abscisic acid receptor related genes were positively associated with the relative abundance of Patescibacteria OTUs upon inoculation of F. mosseae. These finding suggested that AMF can enhance P. frase Cd uptake by modulating plant gene expression and altering the structure of the soil microbial community. This study provides a theoretical basis for better understanding the relationship between root-associated microbiomes and root transcriptomes of P. frase, from which a cost-effective and environment-friendly strategy for phytoextraction of Cd in Cd-polluted soil might be developed.


Subject(s)
Cadmium , Humans , Microbiota , Mycorrhizae , Photinia , Soil Pollutants , Transcriptome
17.
Acta Pharmaceutica Sinica ; (12): 1459-1464, 2022.
Article in Chinese | WPRIM | ID: wpr-924747

ABSTRACT

A method to measure the antibody-dependent cell-mediated phagocytosis (ADCP) potency of anti-CD38 mAb was developed based on design of experiment (DoE) with a Jurkat/NFAT/CD32a-FcεRIγ transgenic cell line as the effector cell, the Daudi cell line as the target cells, and luciferase as the detection system. The DoE method was used for optimization of experimental parameters and methodological validation. The results show that anti-CD38 mAb exhibits a dose-response relationship with the following four-parameter equation: y = (A - D) / [1 + (x / C)B] + D. Several experimental parameters were optimized by statistical experimental design and determined as follows: the working concentration of anti-CD38 mAb was 800-20.81 ng·mL-1, the density of the target cells was 7.5×104 per well, and the density of effector cells was 2.5×104 per well, with an induction time of 6 h. The method showed good specificity. The recovery rate for samples from 5 different groups showed that the relative potencies of anti-CD38 mAb were (59.97 ± 4.74) %, (82.44 ± 5.15) %, (110.69 ± 11.71) %, (129.23 ± 5.22)% and (162.15 ± 3.66) %. The recoveries ranged from 103% to 120% and the RSDs of the above results were all less than 11%. The linear detection range was 50%-150%. Based on DoE design, this method for measuring ADCP potency of anti-CD38 mAb was optimized and validated with good specificity, repeatability and accuracy. This method can be used for evaluation of ADCP biological activity of anti-CD38 mAbs.

18.
Article in Chinese | WPRIM | ID: wpr-924033

ABSTRACT

Objective To analyze the effect of HIV/AIDS patients receiving antiretroviral therapy (ART) for the first time in Jiangyin, and to provide a reference for further improvement of Jiangyin's AIDS antiretroviral treatment. Methods The historical cards and related information in the treatment management database of Jiangyin City's cases who received ART for the first time from 2005 to 2019 were collected and statistically analyzed. The changes in viral load and CD4+ T lymphocytes (CD4 cells) before and after treatment were compared. Results Among 652 patients receiving ART, 507 cases (77.76%) were successful in virological treatment. The median natural change rate of annual average CD4 cell count was 90.8 cells/μL/year (χ2=37.915, P2=10.713, P<0.05; H =10.394, P<0.05) and different baseline CD4 count layers. The results showed that age and baseline CD4 value were the influencing factors of treatment effect. Conclusion Age and baseline CD4 value can affect the effect of ART treatment. The older the age and the lower the baseline CD4 value, the worse the virological efficacy and the recovery effect of CD4 cells. It is suggested that the infected patients should be involved in ART in time, which is conducive to shorten the time of initial treatment and further improve the effect of antiviral treatment.

19.
Organ Transplantation ; (6): 371-2022.
Article in Chinese | WPRIM | ID: wpr-923584

ABSTRACT

Objective To investigate the role of tolerogenic dendritic cell (tolDC) in inducing immune tolerance in liver transplantation. Methods Liver transplantation rat models of spontaneous tolerance [Brown Norway (BN)→Lewis, tolerance group, n=6] and acute rejection (AR) (Lewis→BN) were established. In AR rat models, tolDC transfusion was performed in the study group (tolDC group, n=6) and no intervention was given in the control group (AR group, n=6). The survival time of rats in each group was observed. The transplant liver tissues of rats were prepared for pathological examination in each group. The expression of myeloid dendritic cell (mDC) and plasmacytoid dendritic cell (pDC) in rat peripheral blood, transplant liver, spleen and lymph nodes in each group was detected by flow cytometry. The expression levels of serum interleukin (IL)-10 and interferon (IFN)-γ in each group were measured by enzyme-linked immune absorbent assay. Results Pathological manifestations of rats in the AR group mainly included inflammatory cell infiltration and tissue structural disorder in transplant liver, and the survival time was 7-14 d. In the tolDC and tolerance groups, the transplant liver tissues were almost normal, and the longest survival time exceeded 100 d. Compared with the AR group, the expression levels of CD11+mDC in peripheral blood, transplant liver, spleen and lymph nodes of rats were significantly down-regulated in the tolerance and tolDC groups (all P < 0.05), and those of CD86 and major histocompatibility complex (MHC)Ⅱon the surface of CD11+mDC were also significantly down-regulated (all P < 0.05). Compared with the AR group, the expression levels of pDC in peripheral blood, transplant liver, spleen and lymph nodes of rats were significantly up-regulated in the tolerance and tolDC groups (all P < 0.05), whereas those of MHCⅡon the surface of pDC were all significantly down-regulated (all P < 0.05). Compared with the AR group, the expression levels of serum IL-10 were significantly up-regulated, and IFN-γ were significantly down-regulated in the tolerance and tolDC groups (all P < 0.05). Conclusions As tolDC subsets, mDC and pDC play a positive role in regulating the incidence of graft immune tolerance in rats after liver transplantation.

20.
Article in Chinese | WPRIM | ID: wpr-923122

ABSTRACT

@#[摘 要] 目前,针对抑制性受体或配体、PD-1/PD-L1及CTLA-4的靶向免疫治疗已经取得了显著的临床成果,然而仍有许多患者未从免疫治疗中获益。因此,有必要寻找新的靶点及治疗方法,以提高免疫治疗的应答率。淋巴细胞上的T细胞免疫球蛋白及其ITIM结构域(T-cell immunoreceptor with immunoglobulin and ITIM domains,TIGIT)、CD226和CD112R等均属于免疫球蛋白超家族受体,与不同配体结合后传递抑制或激活信号,他们复杂的相互作用形成的整合信号能够调节免疫细胞的功能。对靶向TIGIT、CD226和CD112R的免疫治疗研究进展进行综述,包括TIGIT、CD226、CD112R的生物学特性,抑制肿瘤或促进肿瘤的机制,靶向治疗的研究进展。

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