NK cells use a variety of receptors to detect abnormal cells, including tumors and their metastases. However, in the case of melanoma, it remains to be determined what specific molecular interactions ...are involved and whether NK cells control metastatic progression and/or the route of dissemination. Here we show that human melanoma cell lines derived from LN metastases express ligands for natural cytotoxicity receptors (NCRs) and DNAX accessory molecule-1 (DNAM-1), two emerging NK cell receptors key for cancer cell recognition, but not NK group 2 member D (NKG2D). Compared with cell lines derived from metastases taken from other anatomical sites, LN metastases were more susceptible to NK cell lysis and preferentially targeted by adoptively transferred NK cells in a xenogeneic model of cell therapy. In mice, DNAM-1 and NCR ligands were also found on spontaneous melanomas and melanoma cell lines. Interference with DNAM-1 and NCRs by antibody blockade or genetic disruption reduced killing of melanoma cells. Taken together, these results show that DNAM-1 and NCRs are critical for NK cell-mediated innate immunity to melanoma cells and provide a background to design NK cell-based immunotherapeutic strategies against melanoma and possibly other tumors.
Premenstrual tension is a common public health problem that significantly affects the personal well-being, academics, and of adolescents’ life quality. Consequently, the purpose of the study is to ...ascertain the prevalence of premenstrual tensions and evaluate its academic and social impact on Iraqi female medical students. From February 2022 to May 2022, a cross-sectional study was carried out at several institutions in Baghdad/Iraq, including (the College of Medicine, Pharmacy, and Dentistry). An online self-questionnaire was used to gather information on the premenstrual tension symptoms, menstrual pain, and academic performance of 2080 Iraqi female medical students. Most respondents (73.6%) experienced various premenstrual symptoms with varying degrees of severity; the most frequent symptoms were depressed mood, anger, irritability, flatulence, acne, and breast tenderness. Approximately (49.0%) of the participants experienced menstrual pain, (78.1%) reported regular menstruation, and (40%) reported learning difficulties. The predominant impact on academic performance was lack of concentration (39.5%) and difficulty in work (34.0%). Among the participants, the majority of the students (59.4%) reported self-medicating with painkillers such as NSAIDs. Furthermore, the study shows that premenstrual symptoms were significantly linked with reduced academic performance and interpersonal relationships among Iraqi medical students (P<0.001). The current study found that premenstrual tension symptoms are associated with poor educational performance and poor interpersonal relationships among Iraqi female medical students. To close the gender gap in our society for a better future, more study is required to analyze and assess the cause of premenstrual tension symptoms and therapeutic interventions.
Bacteria-specific uptake rates of three different protozoan taxa on a pure and mixed bacterial community was studied by means of a simplified and functionally reproducible experimental model. The ...bacterial species
Shigella flexneri
,
Escherichia coli
and
Salmonella typhi
were isolated and classified from stool samples of patients suffering from diarrhea.
Paramecium caudatum
,
Tetrahymena pyriformis
and
Halteria grandinella
, free living ciliate Protozoans, were isolated and identified from Tigris river water. Pure and mixed (
E. coli
+
S. typhi
), (
E. coli
+
Sh. flexneri
) bacterial cultures were used with each ciliate genera to evaluate the following: predator duplication rate, prey reduction rate, clearance rate and net grazing rate. We used selective lactose fermentation phenomena of enteric bacteria on MacConkey medium for the quantification of bacteria cultural characteristics. The final bacteria concentration was reduced by growing protozoa of 98–99.9 % compared to protozoa-free controls. It showed that
Tetrahymena pyriformis
had the highest duplication rate (4.13 time/day) in both types of cultures (pure and mixed), followed by
Paramecium caudatum
and
Halteria grandinella,
respectively.
Paramecium caudatum
had the highest rate of ingestion in both types of cultures (26 × 10
3
bacteria/organism/hr) and yielded the longest time required for 90 % bacterial reduction in a pure suspension of
S. typhi
(166 h). Clearance rates of pathogenic bacteria by ciliates ranged between 106 nanoliter/organism/h by
P. caudatum
to
S. typhi
and 1.92 nanoliter/organism/h seen in
T. pyriformis
in (
E. coli
+
S. typhi
) mixed culture. We used aquatic experimental microcosms under controlled conditions to explore bacteria-dependent ciliate growth and examined whether these ciliates could discriminate between equally sized bacterial preys in a mixture.
Early hematopoietic zinc finger/zinc finger protein 521 (EHZF/ZNF521) is a novel zinc finger protein expressed in hematopoietic stem and progenitor cells and is down-regulated during their ...differentiation. Its transcript is also abundant in some hematopoietic malignancies. Analysis of the changes in the antigenic profile of cells transfected with EHZF cDNA revealed up-regulation of HLA class I cell surface expression. This phenotypic change was associated with an increased level of HLA class I H chain, in absence of detectable changes in the expression of other Ag-processing machinery components. Enhanced resistance of target cells to NK cell-mediated cytotoxicity was induced by enforced expression of EHZF in the cervical carcinoma cell line HeLa and in the B lymphoblastoid cell line IM9. Preincubation of transfected cells with HLA class I Ag-specific mAb restored target cell susceptibility to NK cell-mediated lysis, indicating a specific role for HLA class I Ag up-regulation in the NK resistance induced by EHZF. A potential clinical significance of these findings is further suggested by the inverse correlation between EHZF and MHC class I expression levels, and autologous NK susceptibility of freshly explanted multiple myeloma cells.
An important checkpoint in the progression of melanoma is the metastasis to lymph nodes. Here, to investigate the role of lymph node NK cells in disease progression, we analyze frequency, phenotype ...and functions of NK cells from tumour-infiltrated (TILN) and tumour-free ipsilateral lymph nodes (TFLN) of the same patients. We show an expansion of CD56dim CD57dim CD69+CCR7+KIR+ NK cells in TILN. TILN NK cells display robust cytotoxic activity against autologous melanoma cells. In the blood of metastatic melanoma patients, the frequency of NK cells expressing the receptors for CXCL8 receptor is increased compared with healthy subjects, and blood NK cells also express the receptors for CCL2 and IL-6. These factors are produced in high amount in TILN and in vitro switch the phenotype of blood NK cells from healthy donors to the phenotype associated with TILN. Our data suggest that the microenvironment of TILN generates and/or recruits a particularly effective NK cell subset.
BACKGROUND: Acute promyelocytic leukemia (APL) is a biologically and clinically distinct subtype of acute myeloid leukemia (AML) Etiological and seasonal factors that play a role in APL still ...unclear. OBJECTIVES: The aim of the study was to retrospectively evaluate the available data to assess the impact of seasonal variations on incidence of APL over a period of 6 years. PATIENTS AND METHODS: A retrospective, observational study based on APL record of a Hematology Nasiriyah Center from January 2014 to January 2020 was processed. The collected data of diagnosed (APL) patients at this center for 6 years was analyzed, and APL presenting in each month of the year was also assessed for any evidence of seasonality. RESULTS: Fifty-eight cases of APL were included in this study: there were 22 males (37.93%) and 36 females (62.07%). The mean age was 31.1 ± 14.4 years (minimum 15 and maximum 67). We found a pronounced peak of APL occurrence in March (within winter and early spring months) and decline in summer to zero point in August, which was repeated periodical all studied 6 years. CONCLUSIONS: Seasonal pattern of APL was observed. Investigation of specific seasonal risk factors would be informative in explaining the etiology behind the observed variation.
An important checkpoint in the progression of melanoma is the metastasis to lymph nodes. Here, to investigate the role of lymph node NK cells in disease progression, we analyze frequency, phenotype ...and functions of NK cells from tumour-infiltrated (TILN) and tumour-free ipsilateral lymph nodes (TFLN) of the same patients. We show an expansion of CD56(dim)CD57(dim)CD69 + CCR7 +KIR+ NK cells in TILN. TILN NK cells display robust cytotoxic activity against autologous melanoma cells. In the blood of metastatic melanoma patients, the frequency of NK cells expressing the receptors for CXCL8 receptor is increased compared with healthy subjects, and blood NK cells also express the receptors for CCL2 and IL-6. These factors are produced in high amount in TILN and in vitro switch the phenotype of blood NK cells from healthy donors to the phenotype associated with TILN. Our data suggest that the microenvironment of TILN generates and/or recruits a particularly effective NK cell subset.
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