Blood Lymphocytes Research Articles

Extracts of Allium species suppress activation of the NLRP3 and AIM2 inflammasomes and formation of radiation-induced micronuclei

AbstractAllium is a plant genus with high medicinal and dietary value, which encompasses commonly used culinary herbs such as scallion, garlic, and onion. In this study, we investigated whether Allium extracts exert protective effects on radiation-induced chromosomal damage in BALB/c mice. The mice were orally administered 200 mg kg−1 Allium extracts (scallion, garlic, and onion) for 6 weeks and exposed to 2 Gy gamma radiation 1 day after the final feeding. Haematological parameters and the number of micronucleated bone marrow polychromatic erythrocytes (MnPCEs) were evaluated. Additionally, we analysed the effects of Allium extracts on inflammasome activation in lipopolysaccharide-primed murine bone marrow-derived macrophages. The Allium extracts increased the numbers of peripheral white blood cells, lymphocytes, neutrophils, and red blood cells; significantly decreased the number of MnPCEs; and suppressed the maturation of interleukin-1β by blocking activation of the NLRP3 and AIM2 inflammasomes.In conclusion, Allium extracts protected the hematopoietic function of bone marrow, reduced radiation-induced formation of micronuclei, and suppressed activation of the NLRP3 and AIM2 inflammasomes. Further research is needed to explore the molecular mechanisms of these effects of Allium.

Identification of cuproptosis-related genes in septic shock based on bioinformatic analysis.

Septic shock is a life-threatening condition characterized by a failure of organ systems and a high mortality rate. Cuproptosis is a new form of cell death that is triggered by copper overload. However, the relationship between cuproptosis-related genes and septic shock remains unclear. The GSE26440 dataset from the GEO database was used to screen differentially expressed genes (DEGs) between control and septic shock samples. Additionally, hub genes related to the progression of septic shock and cuproptosis were screened by Venn analysis. RT-qPCR was utilized to validate the expression of hub genes in peripheral blood lymphocytes from septic shock patients and healthy controls. Next, functional analysis and immune cells infiltration were performed. SLC31A1 and MTF1 levels were obviously elevated and LIAS and LIPT1 levels were downregulated in septic shock samples, compared to normal controls. The diagnostic values of the four genes were confirmed with receiver operating characteristic (ROC) curves. Additionally, SLC31A1 and MTF1 showed a positive correlation with natural killer cells and LIAS and LIPT1 exhibited a positive correlation with CD8+ T cells. Furthermore, compared to low-level groups, MAPK signaling was activated in the high-SLC31A1 level group, VEGF signaling was activated in the high-MTF1 level group and lipoic acid metabolism was activated in high-LIAS and high-LIPT1 level groups. This study demonstrates that SLC31A1, MTF1, LIAS, and LIPT1 are dysregulated in septic shock samples, and these genes exhibit potential diagnostic efficacy in septic shock, suggesting that these genes may be potential biomarkers for the diagnosis of septic shock.

Evaluation of Metastasis Inhibition by ABD-IL-2 Compared to Human IL-2 in a Breast Cancer Mouse Model.

Interleukin-2 (IL-2) is a well-known cytokine that plays a crucial role in stimulating immune cells, including natural killer (NK) cells and cytotoxic T cells. It has been studied as an immunotherapy for a variety of diseases, including cancer. However, due to its short serum half-life, high doses of IL-2 are required which can result in systemic toxicities like capillary leak syndrome. To demonstrate the enhanced antitumor efficacy of Albumin Binding Domain-conjugated IL-2 (ABD-IL-2) at a lower dose compared to IL-2. IL-2 and ABD-IL-2 were purified using Ni-NTA resin with a histidine sequence added to their C-terminal region for purification purpose. Peripheral blood lymphocytes were stimulated with IL-2 and ABD-IL-2 to assess their function. 4T1 cells were injected into BALB/c mice to establish a breast cancer model with metastasis evaluated in the lungs. Both recombinant proteins significantly stimulated T lymphocyte proliferation compared to the negative control (P=0.000, P=0.001). Administration of both proteins reduced the size of isolated tumors in the breast cancer mouse model. The control group had more nodules and larger lung metastatic centers (P=0.000). Metastasis to secondary lymphoid organs occurred only in the control group. By using ABD-IL-2 at a one-third concentration compared to IL-2, we aimed to reduce administration toxicity associated with high doses of IL-2 in immunotherapy. This approach shows potential for improving IL-2-based treatments while minimizing adverse effects.

Enhanced Growth, Haematological and Biochemical Performance in Hybrid Catfish of Clarias gariepinus x Clarias cavernicola

This study evaluated the growth performance, haematological indices, and biochemical parameters of four catfish breeds, including two purebreds (Clarias cavernicola and Clarias gariepinus) and two hybrids (female C. cavernicola x male C. gariepinus and female C. gariepinus x male C. cavernicola). Over four months, growth was assessed by measuring body weight, total length, and standard length. Haematological and biochemical analyses were conducted to assess the health and immune status of the different breeds. The results indicated that the hybrid of female C. cavernicola x male C. gariepinus exhibited the highest growth performance, with significant increases in body weight and length compared to the other breeds. This hybrid also demonstrated the highest white blood cell (WBC) and lymphocyte counts, suggesting a stronger immune response, which was statistically significant (p<0.05) compared to the purebreds. Granulocyte levels were consistent across all breeds, while red blood cell (RBC) and platelet counts showed no significant differences, indicating stability in these parameters. Biochemical analysis revealed that the female C. cavernicola x male C. gariepinus hybrid had the highest total protein and globulin levels, which are indicative of better health and immune function. Albumin levels were higher in both hybrids compared to the purebreds, while cholesterol, creatinine, and glucose levels were similar across all breeds. The alleles associated with better immunity are likely present in the maternal line of C. cavernicola, leading to the superior vigour observed in the C. cavernicola (female) x C. gariepinus (male) hybrid. This enhanced vigour results in improved growth, hematological, and biochemical profiles. Compared to purebred breeds, this hybrid demonstrates better health, increased disease resistance, and a higher potential for productivity in aquaculture.

Siwu decoction mitigates radiation-induced immune senescence by attenuating hematopoietic damage

BackgroundTo investigate the long term effects of ionizing radiation (IR) on hematopoietic stem/progenitor cells (HSPCs), immune tissues and cells, and the effects of Siwu decoction (SWD) on immune senescence mice.MethodsC57BL/6 J mice were exposed to 6.0 Gy 60Co γ irradiation. After 8-weeks of IR, SWD (5, 10, 20 g/kg/d) was administered for 30 days. The changes of HSPCs in bone marrow (BM) and T, B type lymphocyte and natural killer (NK) cells in spleen were detected by flow cytometry. The changes of peripheral blood cells were also examined. Hematoxylin–eosin staining were used to detect the pathological lesions of hippocampus, spleen and thymus tissues. Absolute mouse telomere length quantification qPCR assay kit was used to measure the telomere length of BM cells. The expression of factors associated with inflammation and aging such as p16, β-galactosidase in spleen, thymus and BM was determined.ResultsAdministration of SWD could increase the proportion of LSK (Lin−, Sca-1 + , c-Kit−), multipotent progenitor cells and multipotent progenitor cells and decrease the proportion of common myeloid progenitors and granulocyte–macrophage progenitors in BM. The proportion of B cells and NK cells in spleen and the content of white blood cells, red blood cells, hemoglobin, lymphocytes and eosinophils in peripheral blood were increased, at the same time, the proportion of neutrophils and monocytes was reduced by SWD. The pathological lesions of hippocampus, spleen and thymus were improved. The expression of p16 and β-galactosidase in spleen, thymus and BM was reduced and shortening of the telomere of BM cells was inhibited after administration. In addition, SWD could reduce the content of Janus activated kinase (JAK) 1, JAK2 and signal transducer and activator of transcription 3 (STAT3) in BM and spleen.ConclusionsSWD could slow down IR-induced immune senescence by improving hematopoietic and immunologic injury. SWD might reduce the inflammation level of BM hematopoietic microenvironment by acting on JAK/STAT signaling pathway, while the immune damage of mice was improved by affecting the differentiation of HSPCs. The remission of hematopoietic and immunologic senescence was further demonstrated at the overall level.Graphical

Impact of Glyphosate herbicide on blood parameters and selected tissues organs of rabbits (oryctolagus cuniculus)

Numerous studies have demonstrated that pesticides are toxic and harmful to human, animal, and environmental health. Glyphosate is the most widely used herbicide globally. This research aimed to assess the impacts of various dosages of glyphosate on rabbits. A total of 30 rabbits were divided into four groups: one control group and three treatment groups, with three concentrations of glyphosate selected as D1 (200 mg/kg/bw). The treatment groups were administered glyphosate at a dosage of 1 mL/day for 6 days per week over 4 weeks. The findings substantially reduced several hematological parameters, including hemoglobin, erythrocytes, leukocytes, hematocrit, and platelets. At the same time, the levels of white blood cells and lymphocytes increased significantly in all glyphosate-treated groups compared to the control group. Additionally, changes were observed in the liver, thymus, and kidney tissues, including alterations in hepatocyte cells, portal blood vessel congestion, inflammatory cell infiltration, and necrosis of sporadic hepatocytes.

Efficient Selection of the 2,4-Dichlorophenoxyacetic Acid Nanobody Gene from the Phage Library Constructed with Sorted Specific Cells and Expression in Plants to Confer Herbicide Resistance.

Immunomodulation in biotechnological processes requires an adequate level of specific, high-affinity recombinant antibodies expressed in the affected cells. Here, we report a new strategy to obtain a sensitive nanobody against the 2,4-dichlorophenoxyacetic acid (2,4-D) herbicide. Unlike the previous methods that used total peripheral blood lymphocytes, specific peripheral lymphocytes stained with a fluorescein isothiocyanate-labeled 2,4-D coating antigen were isolated via fluorescence-activated cell sorting and used for phage display library construction. This strategy significantly reduced interference of anticarrier protein nanobody phages to small-molecule nanobody development and required only two cycles of panning to obtain the desired positive clones. Nb4-11, one of the most sensitive phage clones, showed good sensitivity and specificity against 2,4-D. Compared with previously reported 2,4-D nanobodies, the sequence of Nb4-11 exhibited completely different complementarity-determining regions (CDRs). The half-maximum inhibition concentration of the Nb4-11-based ic-ELISA was 29.3 ± 1.9 ng/mL. The Nb4-11 gene was subsequently transferred into Arabidopsis thaliana to confer herbicide resistance, and homozygous transgenic T3 lines were obtained. Stable expression of the 2,4-D nanobody in the model plant was confirmed via PCR, ic-ELISA, and Western blot analysis. In the dose-response bioassay, the transgenic T3 lines were resistant to 2 g of 2,4-D ai/ha. This work offers a new way to sort specific peripheral lymphocytes, efficiently develop nanobodies against small molecules, and create a novel mechanism for herbicide resistance based on the expression of nanobodies in plants.

INFLUENCE OF INTERLEUKIN-2 AND INTERFERON-α ON LYMPHOCYTE AGGREGATION AND LYMPHOCYTE-PLATELET CLUSTER FORMATION

The aim of the research was to study the direct and platelet-mediated intercellular adhesion of blood-derived lymphocytes, as well as the influence of interleukin-2 and interferon-α on it.Materials and methods. Whole blood samples from 34 apparently healthy individuals were collected using vacuum tubes containing sodium citrate (3,8%). A suspension of lymphocytes and platelets was isolated on a Ficoll-Urografin gradient. Light microscopy was used to determine the percentage of lymphocyte-platelet aggregates. The effect of cytokines was studied by adding human recombinant interleukin-2 and interferon-α to whole blood, and incubating for 4 hours in a thermostat at 37 °C. After incubation the necessary parameters were counted using the method described above. The results were expressed as mean values and standard deviations (± SD). Statistical processing of the data was performed using the Mann-Whitney U-test and the Kolmogorov criterion (Statistica 10), with differences considered significant at p < 0.05.Results. The study showed that in addition to lymphocyte-platelet aggregates (11 ± 3.6%), the total pool of lymphocytes also contained intercellular aggregates of lymphocytes (3 ± 3,8 per 100 cells) and lymphocyteplatelet clusters (2 ± 0,6 per 100 cells). It was found that the addition of interleukin-2 (IL-2) led to an increase in lymphocyte-platelet aggregates (LPA) and lymphocyte-platelet clusters by 1,8 times (p < 0,001) and 3,3 times (p < 0,001), respectively, compared to the control group. In contrast, incubation of blood samples with interferon-α (IFN-α) led to a decrease in the number of LPA (by 5.5 times compared to the control, p < 0,001) and almost prevented the ability of lymphocytes and platelets to form clusters. The presence of the abovementioned cytokines in the incubated blood did not affect the ability of lymphocytes to form aggregates with each other.Сonclusion. It was found that IL-2 increases the ability of lymphocytes and platelets to form clusters, while IFN-α significantly reduces this ability and has an inhibitory effect on the ability of these cells to form LPA. In our opinion, it is important that the effects of these cytokines were manifested only upon contact of lymphocytes with platelets.

Effects of 660 nm red light and 850 nm near infrared light on human blood lymphocytes

Abstract The applications of light emitting diodes (LED) as a red light therapy (RLT) source for the management of various conditions such as wound treatment, control of inflammation and pain have been growing continually. Despite its extensive medical application, the effects of RLT on living cells are still highly contested. This study is conducted to test the effects of RLT using combined LED source with 660 nm (red) and 850 nm (near infrared) light on cultured human lymphocytes in vitro. To analyze the effect of RLT on human peripheral blood lymphocyte’s proliferation, the mitotic index (cytostatic effect) is monitored under different irradiation exposure time parameters and conditions. This value indicates how a particular treatment affected cell division, either proliferatively, inhibitory, or had no effect at all. The interpretation of the results of the mitotic index is done in relation to the mitotic index of the untreated (unirradiated) control cells. Our data shows higher lymphocyte proliferation for all of the irradiated samples, and is particularly enhanced by multiple exposures to red light. The effectiveness of RLT on cell activity is of importance in determination of suitable treatment for diseases related to the immune system. To better understand the molecular and metabolic mechanisms involved in red LED-induced photobiomodulation, the study will be extended to investigate the RLT effect on cell protein synthesis.

Evaluation of Treatments with Radiotherapy Alone and Radiotherapy Plus Chemo-immunotherapy in Patients with Primary Liver Cancer based on Blood Biomarkers.

It is critical to assess primary liver cancer patients likely to benefit from radiotherapy (RT) or RT plus chemo-immunotherapy. Many potential peripheral biomarkers from blood samples have been proposed for clinical application. Therefore, the aim of this study was to evaluate treatments with radiotherapy alone and radiotherapy plus chemo-immunotherapy in patients with unresectable primary liver cancer based on blood biomarkers. From January, 2017, to February, 2022, 63 unresectable primary liver cancer patients receiving radiotherapy alone (RT, n = 21) or radiotherapy plus chemo-immunotherapy (RT plus C/IT, n = 42) were included in this study. We compared the clinical outcomes and adverse effects of these two groups. Also, distant metastasis-free survival (DMFS), overall survival (OS), and progress- free survival (PFS) were retrospectively analyzed. Finally, univariable and multivariable Cox analyses were used to explore the prognostic role of blood biochemical biomarkers. In this study, 1, 2, and 3 years of OS after RT treatment were 63.9%, 27.0%, and 13.5%, and after RT plus C/IT were 68.2%, 37.0%, and 24.7%, respectively (p = 0.617). Compared with baseline, white blood cells (WBC) and lymphocytes were significantly decreased after RT (p = 0.002 and p = 0.001, respectively) or RT plus C/IT therapy (p = 0.135 and p<0.001, respectively). In multivariable Cox regression analyses, higher lymphocyte counts before RT (pre-Lymphocyte) were associated with better OS and PFS (HR=0.439, p = 0.023; HR=0.539, p = 0.053; respectively), and higher lymphocyte counts before RT (pre- Platelets) were a poor prognostic factor associated with DMFS (HR=1.013, p = 0.040). Importantly, OS and PFS were significantly better for patients (pre-Lymphocyte ≥1.10 x 109/L) (p = 0.006; p = 0.066, respectively). The DMFS was significantly better for patients (pre-platelets < 233.5 ×109/L) (p<0.001). Our evaluation of blood biomarkers before and after radiotherapy or plus chem-immunotherapy for primary liver cancer revealed a potential marker for clinics to decide on precise treatment strategies.

Co-Administration of Hibiscus sabdariffa linn and Daflon-500® mitigates weight loss, hyperglycemia, hematological and oxidative changes in male rats with type-2 diabetes

BackgroundDiabetes mellitus is a complex metabolic disorder associated with persistent hyperglycemia and metabolic imbalance. Flavonoid compounds possess notable qualities in mitigating diabetes and its complications. AimHibiscus sabdariffa linn and daflon-500® were assessed for their effects on body weight, blood glucose/indices, and oxidative changes in type-2 diabetes rats over 28 days. Methods35 male rats were randomly divided into seven groups (n=5). Diabetes mellitus was induced in groups 2-7 via a single intraperitoneal injection of streptozotocin (STZ; 55mg/kg). Group 1(DW) received distilled water (2mL/kg) only. Group 2 (STZ; untreated), group 3 {MET; metformin (200mg/kg)}, group 4 {HS; Hibiscus sabdariffa (400mg/kg)}, group 5 {DAF; daflon-500® (1000mg/kg)}, group 6 {DAF+HS; daflon-500® (1000mg/kg) and Hibiscus sabdariffa (400mg/kg)}, group 7 {DAF+MET+HS; daflon-500® (1000mg/kg), metformin (200mg/kg), and Hibiscus sabdariffa (400mg/kg)}. Body weight and blood glucose were assessed fortnightly. Blood and hepatic/pancreatic tissues were collected for hematological and antioxidant testing. ResultsGroups 2-7 revealed a significant (P<0.05) decrease in body weight on day 14 compared to the increased growth rate observed on day 28 (Group 7).Blood glucose levels significantly increased on days 1 and 14 in groups 2-7 but declined on day 28 in groups 4-7. Significantly higher packed cell volume, hemoglobin levels, red blood cell counts, lymphocytes, and mean corpuscular hemoglobin were observed in groups 5-7. Platelet counts were higher in Groups 2 and 5. Untreated group 2 exhibited considerably reduced catalase activity, glutathione, and malondialdehyde concentrations compared to the treated groups. ConclusionHibiscus sabdariffa linn and Daflon-500® expressed substantial hypoglycemic, antioxidant, and hemato-protective effects.

The immunomodulatory and antioxidative effects of curcumin-supplemented diets against the isolated Aeromonas hydrophila in Oreochromis niloticus.

Worldwide, Aeromonas hydrophila (A. hydrophila) has become a significant foodborne pathogen, causing gastrointestinal and extra-intestinal infections in humans as well as severe economic losses in fish farms. Thus, we conducted this research in two experiments. The experiment 1 investigated the prevalence of A. hydrophila among Nile tilapia in different farms in Kafrelsheikh province and its pathogenicity by detecting some of its virulence genes before being used in the in vivo experiment. The experiment 2 was done to investigate the effect of dietary curcumin on growth performance, humoral immunity, antioxidants, and histopathology of Nile tilapia through a sixty-day feeding trial. Nile tilapia was divided into 3 groups, each in 3 replicates. Fish were given diets that included 0.0 (C, control), 1% (10 g curcumin/kg diet; G1), and 2% curcumin /kg diet (20 g curcumin/kg diet; G2). Moreover, the antibacterial effect of dietary curcumin against isolated bacteria in experiment 1 was investigated through experimental infection. The study's findings of experiment 1 indicated that the incidence of isolated A. hydrophila was 28%. Moreover, the virulence aerolysin (aerA) and haemolysin (hlyA) genes were found in 100% and 50% of the isolates, respectively. The experiment 2 outcomes demonstrated that the growth-modulating impacts of dietary curcumin were notably noticed in final weight, feed intake, weight gain%, and specific growth rate without pathological lesions in the different organs. In addition, the white blood cell and lymphocyte counts significantly (P < 0.05) increased in Nile tilapia fed dietary curcumin. Similar improvements in humoral immunity (lysozyme and phagocytic activity) and antioxidants (catalase and superoxide dismutase) were seen in the 1% curcumin group (G1). The experimental infection with a virulent strain of A. hydrophila that was previously isolated in experiment 1 showed a significant decrease in the morbidity and mortality rates in the 1% curcumin treatment group (G1), followed by the 2% group (G2). The present study concluded that under current experimental conditions, dietary curcumin at a dose of 10 g/kg diet proves effective, but the dose of 1% may not be optimal for tilapia.

ТРАНСЛОКАЦИИ ХРОМОСОМ В ЛИМФОЦИТАХ ПАЦИЕНТКИ В ОТДАЛЁННЫЕ СРОКИ ПОСЛЕ АВАРИЙНОГО ЛОКАЛЬНОГО ОБЛУЧЕНИЯ

Objective: to compare the frequencies of translocations detected by one-color and three-color FISH painting in the long term (24 years) after local over-irradiation (more than 100 Gy) of a patient during radiation therapy for breast cancer. Material and methods: The material for the cytogenetical study were the cultures of venous blood lymphocytes of this patient. Cultivation of lymphocytes and preparation of chromosome preparations were carried out using variants of standard methods. Chromosomes were stained separately with one-color or three-color DNA probes for 1, 4 and 12 pairs. In both cases, 1000 metaphases were analyzed. Results: In the present study, when using the one-color FISH-method, the frequency of detected reciprocal translocations was 0.5 per 100 analyzed cells, while with tricolor painting they were 2.2 times higher (1.0 per 100 metaphases). When using the available linear-quadratic dose dependence, the average dose to the whole body was estimated at 0.28 Gy, which is a consequence of the local nature of radiation damage, the death of lymphocytes in the zone of high-dose radiation damage and the obvious impossibility of their division. Conclusion: The study of the frequency of chromosomal translocations in the long term after local overexposure during therapy in a patient for breast cancer using a three-color FISH-analysis is a more sensitive method in comparison with a one-color variant of FISH-painting.

РЕЗУЛЬТАТЫ ДЛИТЕЛЬНОГО МЕДИЦИНСКОГО НАБЛЮДЕНИЯ НЕПОСРЕДСТВЕННЫХ УЧАСТНИКОВ АВАРИИ НА ЧАЭС В РОССИЙСКОЙ ФЕДЕРАЦИИ

Purpose: to present the materials of long-term (38 years) monitoring of the health status of a group of patients who had underwent acute radiation syndrome (ARS) in 1986 as a result of the Chernobyl accident and had been living in the territory of the Russian Federation. Materials and methods: the results of cytogenetic dynamic observation of 74 direct participants in the Chernobyl accident who had been examining at the clinic in the period from 1986 to 2012, as well as the results of dynamic inpatient observation of 10 of them permanently residing in Moscow, are summarized. Medical supervision consisted of annual planned hospitalizations in connection with patient requests, or emergency hospitalizations in connection with the detection of acute or exacerbation of a chronic disease. Laboratory and instrumental examination of organs and organ systems critical to the effects of radiation, as well as an extended cancer search, was carried out. Results: according to cytogenetic studies for all degrees of severity of ARS, starting from the 1st degree, the frequency of translocations in blood lymphocytes significantly exceeds the spontaneous level. The initial level of translocations depends on the initial dose estimate. The time of decrease in the frequency of translocations due to the presence of part of the translocations in unstable cells, from the initial value to an established constant level, apparently occurs in the first 5-8 years. Analysis of individual blood curves revealed transient moderate cytopenia, most often thrombocytopenia. Myelodysplastic syndrome (MDS) and leukemias were detected in 5 patients (2- Moscow group, 3- Ukranian group) from the entire group who underwent ARS as a result of the Chernobyl accident, which significantly exceeds the expected level. The diagnosis of radiation cataract was established in 11 patients. Two patients underwent surgical treatment. In the acute period ARS local radiation injuries (LRI) was detected in 59 patients. By 2005, 38 patients with the effects of LRI were observed (33 in Ukraine and 5 in Moscow). The most severe long-term consequences in the form of pronounced cicatricial atrophic changes, radiation fibrosis, and late radiation ulcers were detected in patients with grade III – IV LRI. 1 out of 10 observed patients developed primary multiple metachronous cancer of the genitourinary system, 2 patients – prostate cancer, 1 – metastatic lesion with an undetected primary tumor, 3 – multiple foci of basal cell skin cancer. The causes of death in 8 out of 10 patients were: cardiovascular pathology, MDS and leukemia, cirrhosis of the liver, oncological disease with undetected primary localization of the tumor, suicide in an oncological patient. Conclusions: The experience of providing medical care to victims of the Chernobyl accident with acute radiation injuries and further in the period of long-term consequences indicates the need to maintain constant readiness to provide medical care in case of a radiation accident, as well as adequate information during and after the accident, which will reduce the long-term consequences. Patients who have undergone ARS need lifelong medical supervision and the provision of necessary medical care. The main causes of permanent disability of patients who have undergone ARS are the consequences of LRI (recurrent late radiation ulcers, radiation fibrosis, contractures, scars, etc.). Radiation cataract is the cause of temporary disability (before surgical treatment). Patients who have undergone ARS need adequate social adaptation. The revealed effect of exposure to relatively uniform radiation is an increase in the frequency of MDS and leukemia.

Associations between blood markers of glucose metabolism and characteristics of circulating lymphocytes

AimsThe pathophysiology of diabetes is not fully understood; recent research indicates close relations with immunological alterations. Therefore, the aim of this study was to investigate the associations between markers of glucose metabolism and characteristics of blood lymphocytes in a population-based cohort. MethodsThe analysis was based on data from 219 non-diabetic participants of the MEGA study in Augsburg, Germany, who were recruited between 2018 and 2021. The majority of participants were examined two different times with a time lag of 9 months. Fasting venous blood samples were taken and oral glucose tolerance tests (OGTT) were performed at both visits. Immune cells were analyzed from fresh blood using flow cytometry. The associations between fasting blood glucose levels, glucose levels at 2 hours after oral glucose bolus and glycated hemoglobin (HbA1c) concentrations and the quantity of different lymphocyte subsets were analyzed using linear mixed regression models with random intercept. P values were FDR-adjusted. ResultsHbA1c was negatively associated with the marginal zone B cells (IgD+ CD27+ B cells). Fasting glucose was positively associated with natural killer (NK) cells and 2-hour OGTT glucose was positively associated with NKT cells. Finally, HbA1c showed significantly negative associations with the CD57-PD1-NKT cell subset. ConclusionMarkers of glucose metabolism showed significant associations with B cell, NK cell and NKT cell subsets, which clearly indicates a relation between glucose metabolism and the adaptive immune system.

Cilostazol geno-protective effects mitigate carbamazepine-induced genotoxicity in human cultured blood lymphocytes

Cilostazol geno-protective effects mitigate carbamazepine-induced genotoxicity in human cultured blood lymphocytes

The involvement of nicotinate and nicotinamide metabolism pathway in attenuating benzene-induced mouse hematotoxicity

Benzene exposure has been linked to various adverse health effects. However, the effective strategy for prevention or treatment of benzene-induced hematotoxicity remains unsolved. We previously administrated hepatocyte-specific deletion of Ppp2r1a gene (encoding PP2A Aα subunit) mice with benzene via inhalation for 28 days, and found homozygote (HO) mice exhibited alleviative hematotoxicity compared with wild type (WT) mice. Here, we integrate untargeted metabolomics and transcriptomics data to identify the key metabolic pathways and metabolites attenuating benzene-induced hematotoxicity. Metabolomics analysis revealed the perturbation of nicotinate and nicotinamide metabolism, as well as taurine and hypotaurine metabolism pathways, were implicated in regulating benzene-induced hematotoxicity. Meanwhile, transcriptome analysis showed that immune-, inflammation-, and metabolism-related pathways were obviously disturbed in WT mice groups upon benzene exposure, while sirtuin signaling pathway, associated with nicotinate and nicotinamide metabolism, was activated in HO mice groups. Notably, combined metabolomics and transcriptomics analysis further confirmed the involvement of nicotinate and nicotinamide metabolism, taurine and hypotaurine metabolism pathways in relieving benzene-induced hematotoxicity. Specific metabolites, including 1-methylnicotinamide (MNA), nicotinamide (NA), β-nicotinamide mononucleotides (NMN), and taurine were identified as the potential metabolites alleviating benzene-induced adverse effects. In vitro experiments demonstrated the protective effect of MNA and NA against 1,4-benzoquinone (1,4-BQ)-caused cytotoxicity in HL-60 cells. In vivo, MNA supplementation in drinking water could effectively restore the decline in white blood cell (WBC), lymphocyte (LYMPH), and reticulocyte (RET) counts, also mitigate oxidative damage and genotoxicity in response to benzene exposure. These observations highlight the potential of MNA supplementation as a strategy for preventing benzene-caused hematotoxicity.

Concomitant telomere attrition is associated with spinal muscular atrophy in highly inbred region of North India: unraveling the thread in Kashmir region

Spinal muscular atrophy (SMA) is a rare genetic disorder that unequivocally results in the degeneration of motor neurons, leading to muscle weakness and atrophy. This condition is caused by a mutation in the survival motor neuron 1 (SMN1) gene, which inevitably results in a deficiency of the SMN protein. In present study, we investigated the potential role of telomere attrition in SMA patients. Relative telomere length in peripheral blood lymphocytes was measured by Monochrome Multiplex Quantitative Polymerase Chain Reaction (MMQPCR) in 98 subjects and we conclusively found that SMA cases exhibit telomere attrition compared to healthy controls (P = 4 × 10− 2). Moreover, significant attrition was also observed in severe form of SMA, i.e. SMA type 0 (P = 0.04) as well.Although, the exact mechanism through which telomere shortening contributes to the pathogenesis of SMA is not fully understood and is yet to be delineated. However, one possibility is that telomere shortening leads to genomic instability and DNA damage, which can contribute to motor neuron degeneration. Another possibility is that telomere shortening leads to cellular senescence, which can impair the ability of motor neurons to regenerate and repair themselves. Recent studies have suggested that telomere shortening may be a potential therapeutic target in SMA. Thus, understanding the role of SMN1 gene in disease pathogenesis & its effect on telomere length will aid in estimating the risk & prognosis of SMA in genetically less explored & highly inbred region of Kashmir, Northern India.

Immune Signatures of Solid Tumor Patients Treated With Immune Checkpoint Inhibitors: An Observational Study.

Our study aimed to comprehensively describe the features of peripheral blood multiple immune cell phenotypes in solid tumor patients during pretreatment and after immunotherapy, providing a more convenient approach for studying the prognosis of immunotherapy in different solid tumor patients. We prospectively recruited patients with advanced solid tumors from Peking Union Medical College Hospital (PUMCH) between February 2023 and April 2024. Using multicolor flow cytometry, our study comprehensively observed and described the signatures of peripheral blood lymphocyte subsets including activation, proliferation, function, naïve memory, and T cell exhaustion immune cell subsets in this population of pretreatment and after immunotherapy. Our study enrolled 59 advanced solid tumor patients with immunotherapy and 59 healthy controls were matched by age and gender. The results demonstrated a marked upregulation in the expression of lymphocyte activation markers CD38 and HLA-DR, as well as exhaustion and proliferation markers PD-1 and Ki67, in solid tumor patients compared to healthy controls. After immune checkpoint blockade (ICB) treatment, mainly the expression of Ki67CD4+T and HLA-DRCD38CD4+T, was significantly upregulated compared to pretreatment levels (p = 0.017, p = 0.019, respectively). We further found that gynecological tumors with better prognoses had higher baseline activation levels of CD4+ T cells compared to other solid tumors with poorer prognoses. Our study elucidated the characteristics of different lymphocyte subsets in the peripheral blood of solid tumor patients. Further research revealed changes in the phenotypes of different lymphocyte subsets after ICIs treatment, with the activated phenotype of CD4+ T cells playing a crucial role in the antitumor effect. This lays the groundwork for further exploration of prognostic biomarkers and predictive models for cancer patients with immunotherapy.

Laboratory Biochemical and Hematological Parameters: Early Predictive Biomarkers for Diagnosing Hepatitis C Virus Infection.

Hepatitis C virus (HCV) infection is a worldwide concern, causing liver damage and necessitating early detection to prevent its spread. Studies indicate that evaluating changes in biochemical and hematological parameters, which serve as suitable predictors of inflammation, can be a reasonable method for diagnosing hepatitis C infection. This study analyzed 100 samples from high-risk patients positively identified via quantitative real-time PCR (qPCR). Anti-HCV titers, biochemical and inflammatory tests, and complete blood cell counts (CBCs) were performed for these individuals. Additionally, 100 HCV-negative individuals with normal laboratory results were selected as the control group. Receiver operating characteristic (ROC) curves were plotted to determine the cutoff values of the laboratory parameters. According to the findings, the age, average white blood cell (WBC) count, platelet-to-lymphocyte ratio (PLR), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), lactate dehydrogenase (LDH), total bilirubin (TBIL), direct bilirubin (DBIL), alkaline phosphatase (ALP), serum glutamic-pyruvic transaminase (SGPT), and ferritin levels were significantly higher in HCV patients. On the other hand, red blood cell (RBC) counts, neutrophils, lymphocytes, hemoglobin-to-platelet ratio (HPR), and iron (Fe) levels were significantly lower in the case group compared to those in the control group (p < 0.05). Furthermore, the ROC curve analysis revealed that lymphocyte count, neutrophil count, and PLR were very strong predictors for hepatitis C infection (p < 0.0001, AUC = 1). The study highlights significant biochemical and hematological differences between HCV patients and healthy subjects. These biomarkers are crucial for early diagnosis, potentially preventing liver damage and reducing HCV transmission.