Decrease In Cell Count Research Articles

Evaluation of the Therapeutic Impact of Probiotic-Enriched Orange and Pomegranate Juices on Some Health Parameters in Diarrhea-Induced Laboratory Rats

This research endeavor was undertaken to craft a functional beverage by blending orange and pomegranate juices, enriched with the inclusion of therapeutic probiotic strains, specifically Lactobacillus acidophilus, Lactobacillus plantarum, and Lactobacillus rhamanous. A comprehensive assessment was conducted to investigate the physicochemical, microbial, and sensory characteristics of the resulting beverage. Furthermore, we explored the potential health benefits of this fortified beverage within a rat model afflicted with E. coli infection, focusing on its influence on blood parameters and lipid profiles in male rats. The research findings revealed the presence of four distinct bacterial strains, namely Staphylococcus hominis, Staphylococcus aureus, E. coli, and Enterococcus gallinarum, in natural juices obtained from local markets in Tikrit. Regarding the physicochemical properties and bacterial counts in the manufactured juices, the results indicated a decline in pH levels and total sugar content over time, coupled with an increase in total acidity during refrigerated storage of functional juices. Additionally, the enumeration and viability of fortifying bacteria surpassed the prescribed probiotic threshold in the tested juice varieties. Sensory evaluation outcomes demonstrated the overall acceptability of the manufactured juices. The research findings demonstrated that E. coli-induced diarrhea led to a significant elevation (P<0.05) in key blood parameters, including white blood cell and platelet counts (12.63 and 747 mm^3/liter), along with a notable reduction in red blood cell counts and hemoglobin concentration (6.0 and 13.1 mm^3/liter, respectively). However, oral administration of functional juices resulted in a decrease in white blood cell and platelet counts and an increase in red blood cell counts and hemoglobin concentration across all measured parameters. Regarding lipid profiles, the diarrheal group exhibited elevated levels of detrimental lipid markers, including cholesterol, triglycerides, and low-density lipids (73.59, 71.61, and 14.8, respectively), accompanied by reduced high-density lipoproteins concentration (31.5). Conversely, treatment with oral doses of functional juices led to a reduction in these adverse lipid indicators for all treatment groups.

Dual Activity of Type III PI3K Kinase Vps34 is Critical for NK Cell Development and Senescence.

Vps34 is the unique member of the class III phosphoinositide 3-kinase family that performs both vesicular transport and autophagy. Its role in natural killer (NK) cells remains uncertain. In this study, a model without Vps34 (Vps34fl/fl/CD122Cre/+) is generated, deleting Vps34 during and after NK-cell commitment. These mice exhibit a nearly 90% decrease in NK cell count and impaired differentiation. A mechanistic study reveals that the absence of Vps34 disrupts the transport of IL-15 receptor subunit alpha CD122 to the cell membrane, resulting in reduced responsiveness of NK cells to IL-15. In mice lacking Vps34 at the terminal stage of NK-cell development (Vps34fl/fl/Ncr1Cre/+), NK cells gradually diminish during aging. This phenotype is associated with autophagy deficiency and the stress induced by reactive oxygen species (ROS). Therefore, terminally differentiated NK cells lacking Vps34 display an accelerated senescence phenotype, while the application of antioxidants effectively reverses the senescence caused by Vps34 deletion by neutralizing ROS. In summary, this study unveils the dual and unique activity of Vps34 in NK cells. Vps34-mediated vesicular transport is crucial for CD122 membrane trafficking during NK cell commitment, whereas Vps34-mediated autophagy can delay NK cell senescence.

Abstract 1334: Evaluation of NK cell combination therapies in mouse models of cancer

Abstract Adoptive immunotherapy with natural killer (NK) cells has emerged as a promising innovative approach against hematological malignancies and solid tumors. To enhance the functional aspects of NK cells and to achieve stronger, sustained anti-tumor responses, combination strategies are under development. They are focused on optimization of NK cell potency, persistence and tumor targeting using monoclonal antibodies, multi-specific NK cell engagers and immune modulators like cytokines. SAR445419 is a universal off-the-shelf allogeneic human NK cell (hNK) product made using Sanofi’s proprietary platform with potential broad application across hematologic and solid tumor indications. We evaluated the therapeutic potential of these NK cells in combination with internal assets and standard of care treatments in preclinical mouse models. The studies were performed in immunodeficient NOG mouse strains transgenic for hIL-15, supporting long-term engraftment of functional hNK cells. We demonstrated the therapeutic advantage of NK cell combination with an anti-CD20 monoclonal antibody (mAb) in a disseminated lymphoma model. We also reported prolonged lifespan of leukemia-bearing animals treated with NK cells and pegenzileukin, a PEGylated non-alpha rhIL-2 variant engineered to preferentially bind to the IL-2 βγ receptors and promote NK cell function. The anti-tumor response correlated with pegenzileukin-induced increase in NK cell numbers in the blood. A combination of CD38KO NK cells with an anti-CD38 mAb was also investigated in a model of multiple myeloma (MM). FcγR-KO immunodeficient mice were used in these studies to limit the confounding contribution of residual murine immune cells engaging with the Fc-competent therapeutic antibody and to specifically detect hNK-cell mediated activity. The comparison of CD38KO versus WT NK cell numbers in the blood of animals treated with an anti-CD38 mAb showed a significant decrease in CD38-expressing NK cell count that was mitigated by the genetic deletion of CD38. Obtained results suggest that CD38KO NK cells are resistant to anti-CD38 mAb-mediated fratricide and provide a rationale for the combination of CD38KO NK cells with anti-an CD38 mAb against MM. Overall, these preclinical in vivo studies have a pivotal role in the evaluation of NK cell combination therapies against cancer and reveal their therapeutic potential. Citation Format: Katarzyna Franciszkiewicz, Pauline Rettman, Beatrice Gauthier, Laurence Noblet, Celine Nicolazzi, Andre Kunert, Rob Igarashi, Loreley Calvet, Valeria Fantin, Sukhvinder Sidhu. Evaluation of NK cell combination therapies in mouse models of cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1334.

Abstract 2777: A unique sub-population of PDGFRB+ glioma-associated mesenchymal stem cells constitute the perivascular niche in murine glioblastoma

Abstract Microvascular proliferation (MVP) and spatial heterogeneity are defining histological features of glioblastoma (GBM). Using ex vivo culture method to analyze human GBMs we have previously identified mesenchymal stem cell (MSC)-like cells, called glioma-associated-MSCs (GA-MSCs) in the heterogenous tumor-microenvironment (TME) of GBMs. Like pericytes, fibroblastic cells and smooth muscle cells (SMCs), these GA-MSCs reside in the perivascular niche (PVN) within GBM, and their presence correlates with MVP, decrease in immune cell counts, and poor prognosis. However, the impact of GA-MSCs on the TME remains correlative, and to date, a causative role of GA-MSCs in MVP and immune evasion has not been established in vivo. We hypothesize that recruited GA-MSCs promote MVP and enhance immune evasion in the GBM-TME. To begin to address this hypothesis, we first identified and characterized GA-MSCs at single-cell resolution in an immunocompetent murine GBM model. We sorted tumor, immune, and non-tumor-non-immune (NTNI) cells from GFP-labelled GSC005 tumors in C57Bl/6 mice and performed scRNA-seq. Tumor cells (GFP+ cells) clustered together into 13 distinct cell states. Of the immune cells (CD45+), the most abundant cell types were microglia (33.9%), macrophages (31.9%), T cells (10.3%), dendritic cells (7.5%) and B cells (1.4%), mimicking human GBM. In the NTNI compartment, we identified 17 clusters, which mapped to endothelial cells, oligodendrocytes, astrocytes and other cell types. Interestingly, there were 4 distinct cell clusters that exclusively expressed platelet-derived growth factor receptor beta (PDGFRB). Three of these clusters mapped to pericytes, SMCs and fibroblastic cells. The fourth cluster expressed both adipose tissue and bone marrow MSC markers, identifying for the first time, GA-MSCs in murine GBM. Next, to define the spatial organization of GA-MSCs and their relationship to immune cells in the GBM TME, we conducted spatial proteomics. GA-MSC counts were significantly higher in the PVN compared with the avascular niche (AN) (p= 0.009) and GA-MSCs were absent in contralateral non-tumor regions. Interestingly, GA-MSCs co-localized with SMCs, fibroblastic cells and pericytes as well as pro-tumorigenic macrophages/microglia (Iba1+/CD163+) in the PVN indicating potential interactions between these cell populations. In conclusion, we have identified for the first time, MSC-like cells in the PVN of murine GBM. Our results suggest that these GA-MSCs are recruited to the TME where they may promote MVP, a hallmark of GBM, and interact with immunosuppressive immune cells. Building on these observations, future experiments will investigate the extent to which GA-MSCs drive MVP formation and immune evasion in GBM. Citation Format: Mohammad F. Zaman, Sanjay K. Singh, Anwar Hossain, Lynette M. Phillips, Joy Gumin, Daniel Ledbetter, Bojana Milutinovic. A unique sub-population of PDGFRB+ glioma-associated mesenchymal stem cells constitute the perivascular niche in murine glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2777.

ASSESSMENT OF COMPLETE BLOOD COUNT AND LIVER ENZYMES IN CHRONIC KIDNEY DISEASE PATIENT

Chronic renal failure (CRF) poses a significant global health challenge, with chronic kidney disease (CKD) characterised by kidney damage or a glomerular filtration rate (GFR) persistently below 60 ml/min for over three months. This observational study, conducted in Faisalabad from January to July 2023, aimed to evaluate haematological variables and liver enzymes across different stages of CKD. Using non-probability purposive sampling, 144 CKD patient files and 48 healthy control files were collected, excluding specific conditions. CKD staging was determined using the Modification of Diet in Renal Disease (MDRD) algorithm, categorizing patients into mild (Group A), moderate (Group B), severe (Group C) CKD, and controls (Group D). Data analysis was performed using SPSS v23. Mean ± SD values were presented for each parameter across the four groups. Haemoglobin levels (Hb g/dl) exhibited a decreasing trend in CKD patients compared to the control group, with values of 13.7 ± 1.50 in controls, 11.7 ± 0.64 in Group 1, 9.7 ± 0.57 in Group 2, and 6.7 ± 1.5 in Group 3. Red blood cell count (RBCs per million/mm3) also decreased progressively in CKD patients compared to controls, with values of 5.48 ± 0.59, 4.62 ± 0.15, 3.57 ± 0.28, and 2.81 ± 0.23 in the respective groups. Conversely, white blood cell counts (WBC thousand/mm3) increased with CKD progression, showing values of 8406 ± 1383 in controls, 10674 ± 1006 in Group 1, 12028 ± 643.5 in Group 2, and 13564 ± 741.29 in Group 3. Similarly, platelet counts (lakh/ul) exhibited a decreasing trend in CKD patients compared to controls, with values of 324708 ± 112970, 235458 ± 63853, 144979 ± 6935.8, and 126333 ± 4768.3, respectively. Analysis of liver enzymes revealed a progressive decrease in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels as CKD advanced. AST levels (U/L) decreased from 29.104 ± 3.130 in controls to 7.5825 ± 1.543 in Group 3, while ALT levels (U/L) decreased from 48.145 ± 4.9679 in controls to 12.270 ± 3.3500 in Group 3. Our findings demonstrate that haemoglobin, red blood cell count, platelet count, and liver enzyme levels (AST and ALT) decrease as CKD progresses while white blood cell count increases. These insights into haematological and hepatic biomarkers underscore the dynamic nature of CKD pathology and may inform clinical management strategies.

DELINEATION OF HEMATOLOGICAL CHANGES OCCURRING IN STORED CITRATE PHOSPHATE DEXTROSE ADENINE CPDA-1 BLOOD

Objectives: To study the changes in red cell indices and counts over a period of 42 days in blood stored in blood bags. Materials and Methods: This research was done in Blood Bank, Khyber Teaching Hospital, Peshawar in collaboration with the main laboratory, Khyber Teaching Hospital, Peshawar. About 450 ml of whole blood was taken from 200 donors into Citrate Phosphate Dextrose Adenine blood bags. The storage temperature for the blood bags was maintained between 2–8°C. Blood samples were collected from blood bags. At days 1 and 42, using a haematology analyser, parameters including haemoglobin, RBC count, WBC count, haematocrit, mean corpuscular volume, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration and platelet counts were measured. Mean and standard deviation were used for quantitative variables. Frequency and percentages were used for qualitative variables. Results: Through days 1 to 42, Haemoglobin (Hb) level decreased from 13.4gm/dl to 12.78 gm/dl, white cell count (WBC) decreased from 6.03x109/l to 2.95 x109/l, platelets count fell from 207 x109/l to 121 x109/l, neutrophils decreased from 59.6% to 23.8% while lymphocyte count increased from 28.36% to 66.3%. Conclusion: There is a decrease in haemoglobin level and white cell count over a period of 42 days of storage of blood bags. Lymphocyte counts increased during the storage duration of blood bags.

Pooled analysis of pralatrexate single-agent studies in patients with relapsed/refractory peripheral T-cell lymphoma

AbstractPatients with relapsed or refractory (R/R) mature natural killer cell and T-cell lymphoma have limited treatment options. To evaluate pralatrexate’s performance and factors influencing its safety and efficacy in R/R peripheral T-cell lymphoma (PTCL), we performed a pooled analysis of data from 4 similarly designed, regulatory-mandated prospective clinical trials. Of 221 patients (median age, 59 years; 67.0% male) in the study population, 48.9% had PTCL not otherwise specified (PTCL-NOS), 21.3% angioimmunoblastic T-cell lymphoma, and 11.8% ALK-negative anaplastic large cell lymphoma (ALCL). Patients received pralatrexate for a median of 2.56 months (range, 0.03-24.18) and had a 40.7% objective response rate with a median duration of response of 9.1 months, progression-free survival 4.6 months, and overall survival 16.3 months. The most common treatment-related all-grade adverse events were stomatitis, thrombocytopenia, white blood cell count decrease, pyrexia, and vomiting. Subgroup exploratory analyses suggest improved efficacy with 1 prior line of chemotherapy vs 2 or ≥4 prior lines; PTCL-NOS or ALCL vs transformed mycosis fungoides; chemotherapy and transplant before pralatrexate vs chemotherapy alone or chemotherapy with other nontransplant treatments. In conclusion, these pooled analysis results further support using pralatrexate in patients with R/R PTCL. Prospective studies are needed to confirm the findings of subgroups analyses.

Characterization of two bacteriophages specific to Acinetobacter baumannii and their effects on catheters biofilm.

Multidrug-resistant strains of Acinetobacter baumannii cause major nosocomial infections. Bacteriophages that are specific to the bacterial species and destroy bacteria can be effectively used for treatment. In this study, we characterized lytic bacteriophages specific to A. baumannii strains. We isolated lytic bacteriophages from environmental water samples and then investigated their morphology, host range, growth characteristics, stability, genome analysis, and biofilm destruction on the catheter surface. Our results showed that the efficacy of the phages varied between 32% and 78%, tested on 78 isolates of A. baumannii; 80 phages were isolated, and two lytic bacteriophages, vB_AbaP_HB01 (henceforth called C2 phage) and vB_AbaM_HB02 (henceforth called K3 phage), were selected for characterization. Electron microscopy scans revealed that the C2 and K3 phages were members of the Podoviridae and Myoviridae families, respectively. Whole-genome sequencing revealed that the sequence of the C2 phage is available in the NCBI database (accession number: OP917929.1), and it was found sequence identity with Acinetobacter phage AB1 18%, the K3 phage DNA sequence is closely related to Acinetobacter phage vB_AbaM_phiAbaA1 (94% similarity). The cocktail of C2 and K3 phages demonstrated a promising decrease in the bacterial cell counts of the biofilm after 4 h. Under a scanning electron microscope, the cocktail treatment destructed the biofilm on the catheter. We propose that the phage cocktail could be a strong alternative to antibiotics to control the A. baumannii biofilm in catheter infections.

Impact of prolonged storage time on homograft ultrastructures: an attempt to find optimal guidelines for homograft processing

According to guidelines, total ischemic time for homografts at processing must be kept short to avoid degeneration. Many homografts are discarded due to practical inability to finish all steps from procurement to cryopreservation within the time limit. Although, several studies have shown that homografts with prolonged ischemic time show adequate quality and performance. Twenty aortic and 12 pulmonary homografts were collected and biopsies were retrieved at preparation (day 0) and after 1, 2, 3, 4, 7, 14, 21, 28, and 60 days in antibiotic decontamination at 4 °C. Biopsies were prepared for light microscopy (LM) and transmission electron microscopy (TEM). Assessment generated scores for cells, elastin, and collagen. Relative differences between times were compared with Wilcoxon signed rank test. Bonferroni corrected p value of 0.0056 was considered significant. LM could only reveal decrease in cell count at 60 days in aortic homografts, no other differences was detected. TEM showed affected cell appearance in day 3 and day 4 and beyond for aortic and pulmonary homografts respectively. Elastin appearance was affected at day 60 for aortic and day 21 for pulmonary homografts. Collagen appearance was affected at day 28 for aortic homografts, with no significant differences in pulmonary homografts. Cell degeneration starts early after homograft procurement, but elastic and collagen fibers are more resistant to degeneration. Overall structure integrity as seen in LM was not affected at all, while TEM could reveal small degeneration signs in individual elastic fibers and collagen bundles at 21 and 28 days respectively.

Effects of full-thickness wedge resection on ocular surface and in vivo confocal microscopy findings in floppy eyelid syndrome patients.

To evaluate the effect of full-thickness wedge resection (FTWR) on ocular surface and in vivo confocal microscopy (IVCM) findings in patients with floppy eyelid syndrome (FES). The study included two groups: a surgical treatment (ST) group (26 eyes) consisting of patients who underwent FTWR surgery, and a conservative treatment (CT) group (30 eyes). Pre-treatment and post-treatment ocular surface disease index (OSDI), tear break-up time (TBUT), corneal fluorescein staining (CFS), IVCM findings along with the body mass index (BMI), FES grade, the presence and the treatment of obstructive sleep apnea syndrome (OSAS) were recorded and compared between the groups. The groups were comparable in terms of BMI, FES grade, and OSAS data. After six months, TBUT in the ST group significantly increased to 12.92 ± 1.15, compared to 8.10 ± 1.60 in the CT group (p = 0.000). The CFS and OSDI scores were significantly lower in the ST group (0.15 ± 0.37, 18.0 ± 8.3, respectively) compared to the CT group (0.90 ± 0.61, 27.3 ± 9.3, respectively) (p = 0.000). IVCM analysis revealed a significant decrease in dendritic cell count (ST: 22.0 ± 12.4, CT: 39.5 ± 15.1, p = 0.000) and nerve tortuosity (ST: 1.38 ± 0.64, CT: 2.00 ± 0.59, p = 0.000), with a significant increase in total nerve density (ST: 4.27 ± 0.83, CT: 3.57 ± 0.90, p = 0.002) in the ST group compared to the CT group after six months. In our retrospective cohort, FTWR surgery was shown to be an effective and reliable surgical treatment for FES, improving both ocular surface and IVCM findings. Patients with moderate to severe stages of FES not responding to conservative treatment may benefit from eyelid tightening.

The efficacy and safety of tinengotinib in patients with heavily pretreated metastatic castration-resistant prostate cancer (mCRPC).

133 Background: Tinengotinib is a spectrum-selective multi-kinase inhibitor that targets cell proliferation, angiogenesis, and immune-oncology pathways by inhibiting Aurora kinases A/B, Janus kinases (JAK), and receptor tyrosine kinases (FGFRs, VEGFRs). It has been reported that the activation of JAK/STAT and fibroblast growth factor receptor (FGFR) signaling drives prostate tumor plasticity. Here we present the preliminary safety and efficacy data of tinengotinib in patients with mCRPC from three early phase clinical trials conducted in the US and China. Methods: Eligible mCRPC patients who have no available standard therapeutic treatment options were enrolled to the three studies. Tinengotinib was given as monotherapy at 8 mg QD, 10 mg QD and 12 mg QD. Efficacy tumor assessments were based on RECIST v1.1 for measurable disease and Prostate Cancer Working Group 3 criteria for non-measurable (bone) disease. PSA50 response was also evaluated. CTCAE v5.0 was used for safety assessments. Results: As of 28AUG2023, 30 patients with mCRPC were treated at dose levels of 8 mg QD (n=1), 10 mg QD (n=19) and 12 mg QD (n=10). Median age was 67 years (range 52-82) with ECOG performance status of 1 in 93% of patients. All patients had at least 2 prior therapies including 77% prior docetaxel, 87% prior abiraterone, and 30% prior enzalutamide. The median follow-up time is 5.4 months. Twenty-two (22) patients were efficacy evaluable, of which 13 were evaluable per RECIST v1.1. Fourteen (14) patients were PSA evaluable. The median radiographic progression-free survival (rPFS) was 5.6 months (95% CI, 3.3-7.3). Overall response rate (ORR) was 46% (6/13) and the disease control rate (DCR) was 85% (11/13). Median duration of response (DoR) was 3.0 months. The PSA50 response rate was 50% (7/14). Treatment-related adverse events (TRAEs) occurred in 28 patients (93%). The most common TRAEs (≥20%) included blood thyroid stimulating hormone increase (43%), anemia (37%), hypertension (27%), aspartate aminotransferase increase (23%), electrocardiogram QT prolongation (20%) and white blood cell count decrease (20%). Conclusions: Tinengotinib safety profile was tolerable and manageable. The preliminary efficacy data showed promising clinical benefit of tinengotinib monotherapy in patients with heavily pretreated mCRPC. Further study of tinengotinib in this disease is warranted. Clinical trial information: NCT03654547 , NCT04742959 , NCT05253053 .

An Assessment of the Viability of Haematological and Haemostatic Parameters of Blood under certain Storage Conditions at the Rivers State University Teaching Hospital Blood Bank in Port Harcourt, Nigeria

Introduction: Despite significant advances in transfusion medicine, concerns about the inherent risks of blood transfusion persist, even under optimal temperature and duration of storage. This makes the evaluation of blood viability a global task (1). Maintenance of adequate temperature is considered a key factor in the viability and quality of stored blood in healthcare institutions. Evaluating the haematological and haemostatic functionality of blood elements at different storage temperature and duration is therefore imperative for improving patient care and resource utilization in Rivers State University Teaching Hospital (RSUTH) blood bank in Port Harcourt.&#x0D; Methods: In this cohort study design, a total of sixteen (16) male and female blood donors in equal proportion of sex and ABO blood groups were randomly selected from the Port Harcourt blood donors' population and recruited as study subjects for this research. A well-structured questionnaire and the immunoassays were used to assess the donors' health and serological status respectively. Also the sample obtained were analayzed by automation and data statistically analyzed using ANOVA.&#x0D; Results: The results of this study shows a statistically significant decrease in white blood cell count from 4.93×109/L ± 0.33 to 2.79×109/L ± 1.68 (p=0.00) and platelet count from 227.38×109/L ± 32.17 to 153.75×109/L ± 58.39 (p=0.00) at day 7. Also, a significant decrease in platelet count from 227.38×109/L ± 32.17 to 141.50±60.92 at day 14. A significant decrease in Fibrinogen from 340.75mg/L±18.69 to 281.2575 mg/L ±46.41 at day 1 and day 14 respectively, and rise in PT and aPTT from 17.02s ±1.28 to 24.31s ±6.67 and 41.25s±3.23 to 46.63s±6.28 at day 14th to day 21 respectively (p=0.00).&#x0D; Conclusion and Implications for Translation: Pooled plasma at 4-60C contain clinically significant amount of coagulation factors up to day 21 in storage. The WBC and platelet is lost within seven day of storage at 4-60C. Lower temperatures, especially freezing at -60°C accelerate the loss of haematological viability of blood especially the depletion of white blood cells and platelets (p=0.00). Antihaemophilic factor and fibrinogen is maintained in FFP at 180 day in storage at -600C.

QL1604 plus paclitaxel-cisplatin/carboplatin in patients with recurrent or metastatic cervical cancer: an open-label, single-arm, phase II trial.

QL1604 is a highly selective, humanized monoclonal antibody against programmed death protein 1. We assessed the efficacy and safety of QL1604 plus chemotherapy as first-line treatment in patients with advanced cervical cancer. This was a multicenter, open-label, single-arm, phase II study. Patients with advanced cervical cancer and not previously treated with systemic chemotherapy were enrolled to receive QL1604 plus paclitaxel and cisplatin/carboplatin on day 1 of each 21-day cycle for up to 6 cycles, followed by QL1604 maintenance treatment. Forty-six patients were enrolled and the median follow-up duration was 16.5 months. An 84.8% of patients had recurrent disease and 13.0% had stage IVB disease. The objective response rate (ORR) per Response Evaluation Criteria in Advanced Solid Tumors (RECIST) v1.1 was 58.7% (27/46). The immune ORR per immune RECIST was 60.9% (28/46). The median duration of response was 9.6 months (95% confidence interval [CI]=5.5-not estimable). The median progression-free survival was 8.1 months (95% CI=5.7-14.0). Forty-five (97.8%) patients experienced treatment-related adverse events (TRAEs). The most common grade≥3 TRAEs (>30%) were neutrophil count decrease (50.0%), anemia (32.6%), and white blood cell count decrease (30.4%). QL1604 plus paclitaxel-cisplatin/carboplatin showed promising antitumor activity and manageable safety profile as first-line treatment in patients with advanced cervical cancer. Programmed cell death protein 1 inhibitor plus chemotherapy may be a potential treatment option for the patient population who have contraindications or can't tolerate bevacizumab, which needs to be further verified in phase III confirmatory study. Trial RegistrationClinicalTrials.gov Identifier: NCT04864782.

Toxicity assessment of perovskite nanocomposites: In vivo study.

Perovskite solar cells display potential as a renewable energy source because of their high-power conversion efficiency. However, there is limited understanding regarding the potential impact of perovskite on human health and the ecosystem. In this study, two sets of male Wistar albino rats received 35 injections of perovskite composite at a dosage of 0.372mg/kg body weight. The animals underwent thorough examinations, encompassing morphometric, hematological, biochemical, histological, and behavioral analyses. Liver, kidney, and testis biopsies were processed and examined histologically. Additionally, two groups of mice (perovskite-treated and control mice, each with n = 10) underwent three behavioral tests: the Elevated Zero Maze test, Marble Burying test, and Light-Dark Box test. Perovskite-treated rats displayed a significant increase in levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, triglycerides, cholesterol, creatinine, blood urea nitrogen, white blood cells, and platelets. However, total bilirubin levels decreased, with no significant alteration in albumin values. Furthermore, exposure to perovskite composite resulted in a slight decrease in lactate dehydrogenase and red blood cell count. Histopathological examination revealed hepatic hydropic degeneration, Kupffer cells hypertrophy and hyperplasia, and renal hydropic degeneration, while testicular tissues remained unaffected. Moreover, behavioral changes were observed in perovskite-treated mice, including depression, anxiety, and compulsive burying activity. These findings suggest that exposure to perovskite can lead to significant hematological and biochemical changes, as well as hepatorenal histopathological alterations and behavioral changes. Additionally, chronic exposure to perovskite materials may induce structural and functional alterations in vital organs.

A potential biomarker of radiosensitivity in metastatic hormone sensitive prostate cancer patients treated with combination external beam radiotherapy and radium-223

PurposeThe ADRRAD trial reported the safety and feasibility of the combination of external beam radiotherapy and radium-223 in the treatment of de novo bone metastatic prostate. This study aimed to determine if any biomarkers predictive of response to these treatments could be identified. Experimental design30 patients with newly diagnosed bone metastatic hormone sensitive prostate cancer were recruited to the ADRRAD trial. Blood samples were taken pre-treatment, before cycles 2 to 6 of radium-223, and 8 weeks and 6 months after treatment. Mononuclear cells were isolated and DNA damage was assessed at all timepoints. ResultsDNA damage was increased in all patients during treatment, with bigger increases in foci observed in patients who relapsed late compared to those who relapsed early. Increases in DNA damage during the radium-223 only cycles of treatment were specifically related to response in these patients. Analysis of hematology counts also showed bigger decreases in red blood cell and hemoglobin counts in patients who experienced later biochemical relapse. ConclusionsWhile some patients responded to this combination treatment, others relapsed within one year of treatment initiation. This study identifies a biomarker based approach that may be useful in predicting which patients will respond to treatment, by monitoring both increases in DNA damage above baseline levels in circulating lymphocytes and decreases in red blood cell and hemoglobin counts during treatment.

An interdisciplinary approach to the management of oncohematological patients with immunodeficiency: clinical cases. A review

Immunodeficiency occurs when one or more immune system components do not function properly, resulting in the body's inability to resist mostly infectious agents. Most cases of immunodeficiency in adults are acquired (secondary), but congenital immunodeficiencies are not uncommon. Primary immunodeficiencies are a heterogeneous group of innate immune errors that result in various clinical and laboratory manifestations. In contrast, secondary immunodeficiencies involve an acquired decrease in immune cell count and/or impairment of their function, commonly associated with an antibody level decrease. Secondary immunodeficiency in patients with B-cell hematological malignancies is a common condition attributed to both hematological malignancy and secondary antitumor therapy-related causes. Paradoxically, immunodeficiency, initially attributed to secondary causes, may be due to a previously undiagnosed primary immunodeficiency. Early diagnosis of immunodeficiency and optimization of management strategies with a multidisciplinary approach are critical to providing the most effective specific treatments and reducing the incidence of infection-related complications and mortality. The article addresses clinical practice, recommendations, and problems of immunodeficiency diagnosis and the effectiveness of immunoglobulin replacement therapy illustrated by clinical cases.

The Ability of Some Clay Minerals and Activated Charcoal to Reduce the Negative Effects of Aflatoxin B1, a Contaminant of Broiler Diet

The research was conducted to determine the effect of four types of clay minerals (Iraqi bentonite, English bentonite, Turkish bentonite, and Iraqi kaolin) and activated charcoal on reducing the negative effects of aflatoxin B1, which contaminates poultry feed at a concentration of 350 ppb. The results showed that the average bird weight reached 1134.5 grams in the aflatoxin treatment alone, with a significant difference compared to the control treatment (1690 grams). Adding English bentonite to the contaminated feed was efficient in reducing the impact of aflatoxin, as the bird weight did not differ significantly from the control treatment and reached 1686.9 grams, followed by Turkish bentonite, with an average bird weight of 1618.8 grams, and then Iraqi bentonite with an average weight of 1533.2 grams. The results also indicated that the relative weights of the liver, spleen, and pancreas increased in birds treated with aflatoxin alone. However, the addition of different clay minerals and activated charcoal led to a decrease in the relative weights of the internal organs. The relative weight of the heart and Proventriculus was not affected by the addition of aflatoxin to the feed. Blood analysis results showed a significant decrease in protein and albumin concentrations in the blood of birds treated with aflatoxin alone compared to the control treatment. Additionally, the different additions of clay minerals and activated charcoal had a positive effect on protein concentrations in the blood. Aflatoxin also caused a decrease in blood hemoglobin and red blood cell counts, an increase in white blood cell counts, and an increase in the Neutrophil/Lymphocyte index in birds treated with aflatoxin. However, blood viscosity did not change between the aflatoxin treatment and the other treatments.

The influence of platelet concentrates with and without metronidazole incorporation pre-centrifuge towards periodontal ligament fibroblast proliferation

Objective: Horizontal centrifugation was believed may improve platelet, leukocyte, and growth factors in the buffy coat. Previous study of platelet concentrates metronidazole incorporation was able to greatly inhibit bacteria. Metronidazole might help the proliferation with its ability to inhibit pro-inflammatory cytokines. This study intended to examine the influence of C-PRF and i-PRF with and without metronidazole incorporation horizontal pre-centrifugation towards periodontal ligament fibroblast proliferation. Material and Methods: 2x104 fibroblast cells on the 96 well plates were added with 1 ml of each buffy coat platelet concentrates. The samples were split into five groups: i-PRF, C-PRF, i-PRF metronidazole, C-PRF metronidazole, and control group. Then monitored after 1 day, 3 days, and 5 days using MTT assays. The data were inspected by Two Way ANOVA Test and Post Hoc Test. Results: The result indicated that cell proliferation of fibroblasts was escalated by the addition of C-PRF, i-PRF metronidazole incorporation, and C-PRF metronidazole incorporation group. While the i-PRF group showed decreasing proliferation cell count. Conclusion: This study assumed that platelet concentrates (i-PRF and C-PRF) with metronidazole incorporation can increase the cell proliferation higher than i-PRF and C-PRF only.

Immune Cell Regeneration and Gaining Strength to Attack Multiple Myeloma Cancer

Multiple Myeloma is a rare cancer that primarily affects plasma cells that differentiate into white blood cells (which have important roles in the immune system such as fighting off infections and diseases). Once these plasma cells are transformed into cancerous cells that invade the space of the bone marrow, there is a prevention of the existence of future healthy immune cells that help the human body systems. Due to these viscous effects of the Multiple Myeloma, the blood cell count decreases and patients’ immunity lowers. The weakened immune systems of patients can attack the components of the treatments which leads to the wastage of money, time, and energy of the patients and the medical professionals. With the current research, patients can gain back strength and improve their immune systems. By the usage of the regeneration of stem cells, immunotherapy to increase the resistance of immune cells against the cancer, Chimeric Antigen Receptor T Cell therapy (or CAR-T Cell Therapy), and monoclonal antibody therapies, patients can gain back strength and improve their immune systems in a way that attacks Multiple Myeloma. Yet there is still growth for improvement, since the process of patients receiving treatments must be repeated multiple times due to the intensity and persistence of this cancer. By studying and researching the effects of Multiple Myeloma on immune cells, this paper’s goal is to find ways to improve current treatments and how to regenerate stronger and healthier immune cells which can resist and potentially defeat Multiple Myeloma Cancer.

Septin11 and Septin 8 Play Critical and Overlapping Roles Murine Stem Cell Function

Septins are highly conserved GTP binding proteins which regulate a variety of cellular functions including cytokinesis, polarity, cell cycle, vesicle trafficking, and exocytosis and are now considered the fourth component of the cytoskeleton. Septins are implicated in T and B cell lymphomas; and acute myeloid leukemias, where they frequently act as fusion partners with the Mixed-Lineage Leukemia (MLL) gene. Previous data in our laboratory led to the discovery of a small molecular inhibitor, DW0254, which inhibits RAS function and its downstream target RhoGTPase, Rac, including the hematopoietic-specific Rac2 GTPase, also implicated in MLL leukemias. The inhibitor leads to apoptosis of leukemia cell lines. Using biophysical methods, we discovered that DW0254 binds both the RAS chaperone, PDE6D, and Septin11, which is a member of the Septin6 family (Sara CN, et al., Blood Cancer 2022). Although Septins have been reported to be involved in function of the RhoGTPase Cdc42 and hematopoietic stem progenitor cell (HSPC) polarity, the role of Septin11 in hematopoiesis has not been reported. Septin11 is a member of the Septin6 family of proteins which consists of Septin6, 8, 10, 11 and 14 with significant homology between family members. Previous data in yeast has hypothesized functional overlap within each family of Septin proteins. To better understand the functional role of Septin11, we created lentivirus vectors tagged with a GFP reporter that contained shmiRs against Septin11. Culture of Septin11 knockdown (Septin11 KD) murine HSPC in IMDM (10ng/ml IL-3, 25ng/ml of SCF, TPO, Flt-3 and IL-6) resulted in an average of 13-fold decrease in cell counts compared to controls (p=0.02) and a decrease in total clonogenic activity (Figure 1) with defects seen in both myeloid (GM) and erythroid (BFU-E) colonies. Reduced clonogenic numbers were accompanied by a significant increase in early apoptotic cells suggesting that Septin11 is important in regulating apoptosis in HSPC. To determine the potential role of Septin11 in more primitive hematopoietic cells, we utilized competitive repopulation assays. Transduced BoyJ HSPC (GFP+ Septin11 KD and BFP+ control, mixed 1:1) were injected into lethally irradiated C57Bl/6 mice. We observed a reduction in multilineage chimerism in the peripheral blood, bone marrow, spleen and thymus in primary transplant recipients after knockdown of Septin11 (Table 1). To better define function in specific hematopoietic populations of HSPC, we performed knockdown in FACS-sorted purified cells. Engraftment studies demonstrated a significant reduction in bone marrow chimerism in primary transplant recipients after knockdown of Septin11 most clearly in LT-HSC and ST-HSC (Table 1) with no statistically significant change in MPP. Therefore, to better study the hematopoietic stem cell compartment, we performed secondary transplants utilizing the cells obtained from primary competitive repopulation assays. We observed an unexpected recovery in engraftment in secondary transplant recipients that was accompanied by an increase in the mRNA expression of Septin8. Since Septin8 and Septin11 are closely related we hypothesized that induction of Septin8 was subserving key functions of Septin11. To test this hypothesis, we created a lentivirus vector that expressed both a shmiR against Septin11 and the Septin8 cDNA. Concurrent overexpression of Septin8 with Septin11 knockdown HSPC caused a significant increase in the total number of colonies compared to controls (Figure 1). These data indicate an important role of Septin11 in murine hematopoiesis and a potential redundant role for Septin8.