Matrin-3 acts as a potential biomarker and promotes hepatocellular carcinoma progression by interacting with cell cycle-regulating genes.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide. The oncogenic role of Matrin-3 (MATR3), an a nuclear matrix protein, in HCC remains largely unknown. Here, we document the biological function of MATR3 in HCC based on integrated bioinformatics analysis and functional studies. According to the TCGA database, MATR3 expression was found to be positively correlated with clinicopathological characteristics in HCC. The receiver operating characteristic (ROC) curve and Kaplan-Meier (KM) curve displayed the diagnostic and prognostic potentials of MATR3 in HCC patients, respectively. Pathway enrichment analysis represented the enrichment of MATR3 in various molecular pathways, including the regulation of the cell cycle. Functional assays in HCC cell lines showed reduced proliferation of cells with stable silencing of MATR3. At the same time, the suppressive effects of MATR3 depletion on HCC development were verified by xenograft tumor experiments. Moreover, MATR3 repression also resulted in cell cycle arrest by modulating the expression of cell cycle-associated genes. In addition, the interaction of MATR3 with cell cycle-regulating factors in HCC cells was further corroborated with co-immunoprecipitation and mass spectrometry (Co-IP/MS). Furthermore, CIBERSORT and TIMER analyses showed an association between MATR3 and immune infiltration in HCC. In general, this study highlights the novel oncogenic function of MATR3 in HCC, which could comprehensively address how aberrant changes in the cell cycle promote HCC development. MATR3 might serve as a prognostic predictor and therapeutic target for HCC patients.

CCR9 overexpression promotes T-ALL progression by enhancing cholesterol biosynthesis.

Introduction: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy of the lymphoid progenitor cells, contributing to ∼ 20% of the total ALL cases, with a higher prevalence in adults than children. Despite the important role of human T-ALL cell lines in understanding the pathobiology of the disease, a detailed comparison of the tumorigenic potentials of two commonly used T-ALL cell lines, MOLT4 and JURKAT cells, is still lacking. Methodology: In the present study, NOD-Prkdc scid IL2rgd ull (NTG) mice were intravenously injected with MOLT4, JURKAT cells, and PBS as a control. The leukemiac cell homing/infiltration into the bone marrow, blood, liver and spleen was investigated for bioluminescence imaging, flow cytometry, and immunohistochemistry staining. Gene expression profiling of the two cell lines was performed via RNA-seq to identify the differentially expressed genes (DEGs). CCR9 identified as a DEG, was further screened for its role in invasion and metastasis in both cell lines in vitro. Moreover, a JURKAT cell line with overexpressed CCR9 (Jurkat-OeCCR9) was investigated for T-ALL formation in the NTG mice as compared to the GFP control. Jurkat-OeCCR9 cells were then subjected to transcriptome analysis to identify the genes and pathways associated with the upregulation of CCR9 leading to enhanced tumirogenesis. The DEGs of the CCR9-associated upregulation were validated both at mRNA and protein levels. Simvastatin was used to assess the effect of cholesterol biosynthesis inhibition on the aggressiveness of T-ALL cells. Results: Comparison of the leukemogenic potentials of the two T-ALL cell lines showed the relatively higher leukemogenic potential of MOLT4 cells, characterized by their enhanced tissue infiltration in NOD-PrkdcscidIL2rgdull (NTG) mice. Transcriptmoe analysis of the two cell lines revealed numerous DEGs, including CCR9, enriched in vital signaling pathways associated with growth and proliferation. Notably, the upregulation of CCR9 also promoted the tissue infiltration of JURKAT cells in vitro and in NTG mice. Transcriptome analysis revealed that CCR9 overexpression facilitated cholesterol production by upregulating the expression of the transcriptional factor SREBF2, and the downstream genes: MSMO1, MVD, HMGCS1, and HMGCR, which was then corroborated at the protein levels. Notably, simvastatin treatment reduced the migration of the CCR9-overexpressing JURKAT cells, suggesting the importance of cholesterol in T-ALL progression. Conclusions: This study highlights the distinct tumorigenic potentials of two T-ALL cell lines and reveals CCR9-regulated enhanced cholesterol biosynthesis in T-ALL.

Prevalence of active trachoma infection and associated factors post-war resettled population in raya kobo districts, North East Ethiopia: A community-based cross-sectional study in 2022.

Background: Active trachoma infection poses a serious threat to public health, particularly for those who live in an unprivileged area and has practiced open-field defecation. This study aimed to estimate the prevalence of active trachoma infection and associated factors in the post-war resettled population in Raya Kobo district, North East Ethiopia: a community-based cross-sectional study in 2022. Methods: A community-based cross-sectional study was conducted among 602 participants randomly selected in 14 slum villages in Raya Kobo from February 16th to March 30th, 2023. After the data was collected using a semi-structured questionnaire and entered into Epi-data version 3.2. The study participants were chosen using a two-stage sampling process. Binary logistic regression was used to identify factors for active trachoma infection. Adjusted odds ratios (AORs) with 95% confidence intervals (CIs) were claimed for the strength of association at p < 0.05. Results: Overall, 602 (99.9%) study participants were included in the final analysis. At the end of the study period, 126 (20.9) participants developed active trachoma infection. On multivariable analysis, were aged ≥45 years (AOR = 7.9, 95% CI = 2.4-25.3), history of eye infection (AOR = 3.7, 95% CI = 2.4-10.4, p = 0.001), were poor wealth index (AOR = 9.2, 95% CI = 2.7-23.7), having separated kitchen (AOR = 4.05, 95% CI = 1.86-8.86), living with animals (AOR = 5.92, 95% CI = 2.31-14.7) and having got administration of mass-drug (AOR = 8.9, 95% CI = 2.36-33.6) were significant risk factors for active trachoma infection. Whereas, face washing practice regularly (AOR = 0.23, 95% CI = 0.127-0.43), and toilet availability (AOR = 0.35, 95% CI = 0.20-0.97) were preventive factors for active trachoma infection. Conclusion: A significant prevalence of active trachoma infection was reported in the area as compared with previous findings and urgent clinical intervention, and the WHO critical SAFE strategies (surgery, antibiotics, facial cleanliness, and environmental improvement) implementation is highly needed in the area. In addition, healthcare providers should focus on information dissemination on proper latrine utilization, and washing the face regularly to prevent active trachoma infection is highly recommended.

Exploring multi-level risk factors and post-war burdens of trachomatous trichiasis among displaced population in Raya Kobo districts, implication for urgent action.

AIM: To estimate post-war burdens of trachomatous trichiasis (TT) and multi-level risk factors among displaced population in Raya Kobo districts, implication for urgent action. METHODS: A community-based cross-sectional study was conducted among 603 participants from randomly selected 14 displaced slums in the Raya Kobo district. The data was collected from February 16th to March 30th, 2023. Study participants were selected using the multistage sampling technique. A structured questionnaire and ophthalmic loupe with ×2.5 magnificence were used to collect from participants. Multi-level binary logistic regression was used to determine associated factors with TT infection. Adjusted odds ratio (AOR) with 95% confidence interval (CI) were claimed for the strength of association at P<0.05. RESULTS: We recruited 602 (99.9%) participants for the final analysis. From the total, 126 (20.9%) and 98 (16.3%, 95%CI: 13.5%-19.4%) participants were diagnosed with active trachoma & TT infection, respectively. Being age ≥45y (AOR=7.9, 95%CI: 2.4-25.3), having multiple eye infections (AOR=2.73, 95%CI: 1.47-5.29), poor wealth index (AOR=9.2; 95%CI: 2.7-23.7) and twice face washing per day (AOR=0.082, 95%CI: 0.03-0.21) has identified as individual as factors for TT infection. Whereas, distance between clean water source ≥10 km (AOR=6.5, 95%CI: 3.9-31.3), and latrine availability (AOR=0.35, 95%CI: 0.21-0.58) were the two community-level factors associated with TT infections. CONCLUSION: The high prevalence of TT infection post-war throughout the study districts indicates a need for urgent clinical intervention in addition to rapid scaling up surgery, antibiotics, facial cleanliness, and environmental improvement (SAFE) strategies, strategy for high-risk population. Age≥45y, distance from the clean water source, poor wealth indexes, and eye infection are identified to be risk factors for TT infection. Furthermore, community-level preventative factors for TT infection are found as latrine availability and face washing practice.

LncRNA15691 promotes T-ALL infiltration by upregulating CCR9 via increased MATR3 stability.

Our previous studies demonstrated that CCR9 plays an important role in several aspects of T-cell acute lymphoblastic leukemia progression and that CCR9 is a potential therapeutic target. However, the underlying mechanism that regulates CCR9 expression remains incompletely understood. In this study, bioinformatics analysis and validation in clinical samples revealed the lncRNA15691 to be positively correlated with CCR9 mRNA expression and significantly upregulated in T-cell acute lymphoblastic leukemia samples and CCR9high T-cell acute lymphoblastic leukemia cell lines. LncRNA15691, a previously uncharacterized lncRNA, was found to be located in both the cytoplasm and the nucleus via fluorescence in situ hybridization assay. In addition, lncRNA15691 upregulated the expression of CCR9 and was involved in T-cell acute lymphoblastic leukemia cell invasion. In vivo experiments showed that lncRNA15691 promoted leukemia cell homing/infiltration into the bone marrow, blood, and spleen, whereas the CCR9 ligand, CCL25, augmented the extramedullary infiltration of CCR9low leukemia cells overexpressing lncRNA15691 into blood, spleen, and liver. Subsequently, RNA protein pull-down assays, coupled with liquid chromatography-tandem mass spectrometry, were used to uncover potential lncRNA15691-interacting proteins, which were then validated by RNA immunoprecipitation. These mechanistic studies revealed that lncRNA15691 upregulated CCR9 expression via directly binding to and stabilizing MATR3 by inhibiting its nuclear degradation mediated by PKA. Collectively, our study revealed a novel mechanism of regulating CCR9 expression and implicated lncRNA15691 as a potential novel biomarker for T-cell acute lymphoblastic leukemia infiltration.

Levetiracetam ameliorates epileptogenesis by modulating the adenosinergic pathway in a kindling model of epilepsy in mice.

Background: Levetiracetam (LEV) has been found to have an antihyperalgesic effect via acting on the adenosine system. However, the effects of LEV on the modulation of the adenosine system in the brain have not been elucidated in the prevention of seizures and epilepsy. The present study aimed to explore the possible LEV mechanisms of action in the adenosine signaling systems in an animal model of epilepsy. Methodology: A docking study was initially performed to determine the possible interaction of LEV with adenosine A1 receptors (A1Rs) and equilibrative nucleoside transporters-1 (ENT1). The experimental study was divided into an acute seizure test (32 mice distributed into 4 groups) and a chronic kindling model study (40 mice distributed into 5 groups), followed by gene expression analysis and immunohistochemistry. The kindling model lasted 26 days and took 13 subconvulsive doses of pentylenetetrazole (PTZ) to completely kindle the mice in the PTZ control group. Gene expression changes in the A1Rs, potassium inwardly-rectifying channel 3.2 (Kir3.2), and ENT1 in the brain tissue samples of the mice following treatment with LEV were analyzed using reverse transcription-quantitative polymerase chain reaction, and immunohistochemistry was performed for the A1R protein expression. Results: Docking studies predicted a significant interaction of LEV with A1Rs and ENT1 proteins. Results from the acute testing revealed that caffeine (100 mg/kg) and 8-cyclopentyl-1,3-dipropylxanthine (25 mg/kg) significantly reversed the antiseizure effects of LEV by reversing the percent protection and shortening the onset of the first myoclonic jerk (FMJ) and generalized clonic seizures (GCSs). In the PTZ-induced kindling, LEV demonstrated an increased gene expression of A1Rs and Kir3.2 in the brain. LEV also significantly reduced the gene expression of ENT1. Furthermore, the immunohistochemical analysis showed that LEV increased the protein expression of A1Rs in the brain. Conclusion: Based on these results, it can be concluded that LEV modulates epileptogenesis by acting on the adenosine pathway in the central nervous system.

Anabolic-androgenic steroid use in a young body-builder: A case report and review of the literature.

Introduction: Anabolic-androgenic steroid (AAS) abuse is routine in athletes to enhance their overall physique. It often leads to detrimental effects, including cardiovascular diseases, hormonal imbalances, and cancer. Our case presentation emphasizes two important aspects: the first is the importance of thorough history taking in correctly diagnosing diseases with multiple etiologies. The second one relates to the reversible and preventable hazards of the increasing incidence of usage of illicit drugs, mainly androgenic anabolic steroids in young adults. Case presentation: We present a case of a 30-year-old male bodybuilder with presenting complaints of increased anxiousness, excessive anger, and dyspnea on minimal exertion. Echocardiogram showed a dilated cardiomyopathy with left ventricular ejection fraction (LVEF) of 20%. The patient was counseled for quitting AAS and symptomatically treated on heart failure management guidelines. He responded well to the management plan and now enjoying a healthy life. Conclusion: It is imperative to raise awareness regarding the substantial adverse effects of AAS abuse that might precipitate severe cardiovascular system complications leading to morbidity and eventual mortality. Most of the times, the pathological changes due to AAS abuse are reversible. This shows a good prognosis and better compliance with the management plan advised to the patients.

TTYH3, a potential prognosis biomarker associated with immune infiltration and immunotherapy response in lung cancer.

PURPOSE: The recognition of new diagnostic and prognostic biological markers for lung cancer is an essential and eager study. It's shown that ion channels play important roles in regulating various cellular processes and have been suggested to be associated with patient survival. However, tweety family member 3 (TTYH3), as a maxi-Cl- channel, its role in lung cancer remains elusive. METHODS: The expression, diagnostic and prognostic efficacy of TTYH3 were analyzed by public databases and clinical samples. Cell functional experiments were used to explore the effects of TTYH3 on cell viability. GO and KEGG enrichment analysis revealed underlying pathways that TTYH3 and its co-expressed genes were enriched in. TIMER, TIDE and R language analyses were used to detect the correlation between TTYH3 and immune infiltration cell and immunotherapy response. RESULTS: TTYH3 was up-regulated in lung cancer tissues compared to normal tissues and possessed a prominent diagnostic and prognostic value. TTYH3 knockdown significantly inhibited the proliferation of lung cancer cells. Enrichment analyses showed that TTYH3 and its co-expressed genes were mainly involved in immune related signaling pathways. Further investigation clarified that TTYH3 had a positive correlation with the infiltration of TAMs, Treg infiltration as well as T cell exhaustion and high TTYH3 expression indicated worse immunotherapy response and shorter survival after immune checkpoint blockade treatment. CONCLUSION: This study not only revealed the diagnostic and prognostic value of TTYH3 but also provided TTYH3-based estimation of immunotherapy response for lung cancer patients, which might provide new strategies like anti-TTYH3 combined with immune therapy for the treatment of lung cancer.

Hematopoietic Stem and Progenitor Cells (HSPCs) and Hematopoietic Microenvironment: Molecular and Bioinformatic Studies of the Zebrafish Models.

Hematopoietic stem cells (HSCs) reside in a specialized microenvironment in a peculiar anatomic location which regulates the maintenance of stem cells and controls its functions. Recent scientific progress in experimental technologies have enabled the specific detection of epigenetic factors responsible for the maintenance and quiescence of the hematopoietic niche, which has improved our knowledge of regulatory mechanisms. The aberrant role of RNA-binding proteins and their impact on the disruption of stem cell biology have been reported by a number of recent studies. Despite recent modernization in hematopoietic microenvironment research avenues, our comprehension of the signaling mechanisms and interactive pathways responsible for integration of the hematopoietic niche is still limited. In the past few decades, zebrafish usage with regards to exploratory studies of the hematopoietic niche has expanded our knowledge for deeper understanding of novel cellular interactions. This review provides an update on the functional roles of different genetic and epigenetic factors and molecular signaling events at different sections of the hematopoietic microenvironment. The explorations of different molecular approaches and interventions of latest web-based tools being used are also outlined. This will help us to get more mechanistic insights and develop therapeutic options for the malignancies.

Insulin receptor substrate 1(IRS1) is related with lymph node metastases and prognosis in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is one of the leading causes of cancer-related mortality globally with a high risk of lymph node metastasis (LNM). In this study, weighted gene co-expression network analysis (WGCNA) showed the identification of 10 modules among which the significant module (turquoise), including 1352 genes, was correlated with LNM. A group 52 overlapping differentially expressed genes (DEGs) was identified based on the comparison of turquoise module with GSE23400 and GSE20347 datasets. Using Ctyohubba plugin, we identified 7 hub genes (ACTG2, SORBS1, MYH11, CXCL12, CNN1, IRS1 and CXCL8). IRS1 displayed significant correlation with metastasis. The decreased expression of IRS1 was also a predictor of poor OS of ESCC patients whereas the hub genes namely ACTG2, MYH11, CXCL8, CXCL12, IRS1 and CNN1 were associated with RFS of ESCC patients. These findings suggest that the altered expression of these hub genes are associated with prognosis and thus can be used as potential biomarkers for ESCC. Moreover, immunohistochemical staining and cell functional experiments displayed that the overexpression of IRS1 was negatively associated with metastasis in ESCC. In general, our research revealed several novel genes in ESCC especially the association of IRS1 with LNM in ESCC, which could provide novel insights into the initiation and progression of ESCC.

Performance of waste plastic bio-oil as a rejuvenator for asphalt binder.

Pavement recycling is actively applied on asphalt roads due to ageing problems associated with bituminous binders when exposed to weathering and trafficking during their service life. Recycling of asphalt occurs through rejuvenator agents. This study utilised bio-oil produced from hydrothermal liquefaction of waste plastic films (linear low-density polyethylene - LLDPE) to rejuvenate laboratory-aged bitumen. Initially, the neat bitumen was aged through thermal ageing (Pressure Ageing Vessel - PAV) and then the aged binder was mixed with bio-oil from waste plastics at 5% and 8% bio-oil (BO) by weight of aged binder. All four binders including neat bitumen, aged bitumen, aged bitumen/BO-5% and aged bitumen/BO-8% were analysed for thermogravimetric analysis, Fourier Transform Infra-Red analysis, rheology in the linear viscoelastic region, multiple stress creep and recovery analysis, and linear amplitude sweep analysis. The ageing of neat binder resulted in hardening of the binder; however, the bio-oil rejuvenator softened the aged binder significantly. The thermo-chemical and rheological performance of aged binder was significantly improved after the addition of bio-oil. The outcomes suggest how bio-oil produced from hydrothermal liquefaction of waste plastics (possibly non-recyclable) may serve as potential rejuvenator for aged asphalt binders in an effort to recycle more using non-recyclable material.

Inhibition of FOXO1­mediated autophagy promotes paclitaxel­induced apoptosis of MDA­MB­231 cells.

Triple­negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, and it often becomes resistant to paclitaxel (PTX) therapy. Autophagy plays an important cytoprotective role in PTX­induced tumor cell death, and targeting autophagy has been promising for improving the efficacy of tumor chemotherapy in recent years. The aim of the present study was to clarify the mechanism of PTX inducing autophagy in TNBC cells to provide a potential clinical chemotherapy strategy of PTX for TNBC. The present study reported that PTX induced both apoptosis and autophagy in MDA­MB­231 cells and that inhibition of autophagy promoted apoptotic cell death. Furthermore, it was found that forkhead box transcription factor O1 (FOXO1) enhanced PTX­induced autophagy through a transcriptional activation pattern in MDA­MB­231 cells, which was associated with the downstream target genes autophagy related 5, class III phosphoinositide 3­kinase vacuolar protein sorting 34, autophagy related 4B cysteine peptidase, beclin 1 and microtubule associated protein 1 light chain 3ß. Knocking down FOXO1 attenuated the survival of MDA­MB­231 cells in response to PTX treatment. These findings may be beneficial for improving the treatment efficacy of PTX and to develop autophagic targeted therapy for TNBC.

Synergy in penicillin, cephalosporin, amphenicols, and aminoglycoside against MDR S. aureus isolated from Camel milk

Abstract This study investigated the synergy testing of penicillin, cephalosporin, amphenicols, and aminoglycoside in the camel milk (n=768 samples), subsequently used for isolation of MDR S. aureus targeting mecA gene. Antibiotic susceptibility of S. aureus showed >90% isolates were sensitive to ciprofloxacin and trimethoprim and resistant against oxacillin, ampicillin, and cefoxitin. Further, 50-85% of the S. aureus were sensitive to gentamicin, oxytetracycline, and chloramphenicol and resistant against cefotaxime, vancomycin, and cefixime. Minimum inhibitory concentration (MIC) of cefotaxime, (C) and ampicillin (A) in combination with gentamicin (G) was reduced by 99.34% and 70.46%, respectively, while with chloramphenicol (Ch), reduction was 57.49% and 60%, respectively. In addition, the Fractional Inhibitory Concentration Index (FICI) of G+A, Ch+C and Ch+G combinations showed synergy against 80%, 60%, and 30% of MDR S. aureus, respectively. Similarly, C+A and Ch+G displayed indifferent interaction against 70 % and 30% of isolates, respectively, while the later showed additive interaction against 10% of MDR S. aureus. Altogether, our results described effective combination of gentamicin and chloramphenicol with ampicillin and cefotaxime to combat MDR S. aureus

The effect of GnRH administration/insemination time on follicular growth rate, ovulation intervals, and conception rate of Nili Ravi buffalo heifers in 7 -day-CIDR Co-synch.

The present study aimed to compare two different insemination times (72 vs 84 h) associated with an ovulation induction (GnRH) in a 7-day CIDR Co-synch to improve the conception rate of Nili Ravi buffalo heifers. Forty Nili Ravi buffalo heifers were randomly separated into two treatments based on artificial insemination (AI) timing (72 vs 84 h). All heifers were subjected to controlled internal drug release (CIDR), containing 1.38 g of progesterone for 7 days. On CIDR removal, both treatments received 150 µg of prostaglandin intramuscularly. In 7-day CIDR Co-synch (n = 20), animals were injected 100 µg of GnRH administration intramuscularly and inseminated concurrently at 72 h after CIDR removal. The remaining half (n = 20) were injected and inseminated concurrently at 84 h of CIDR removal. Pregnancy diagnosis was performed on day 40 of timed artificial insemination (TAI) with ultrasound. The follicular growth rate between 72 h after PGF2α/CIDR removal to pre-ovulatory follicle in 7-day CIDR Co-synch was more (0.102 ± 0.005 mm vs 0.079 ± 0.003 mm; P = 0.01) at 84 than 72 h. The interval from GnRH administration/TAI to ovulation was high (26.8 ± 1.64 h vs. 15.1 ± 1.25 h, P = 0.01) in 72 than 84 h. Conception rates were considerably higher in buffalo heifers inseminated at 84 h (65%) than 72 h (25%) in 7-day CIDR Co-synch protocol. In conclusion that in Nili Ravi buffalo heifers, GnRH administration/TAI after 84 h of CIDR removal allows greater follicular growth rate and shortens interval from AI to ovulation compared to the GnRH administration/TAI after 72 h of CIDR removal in 7-day CIDR-Co-synch protocol.

Recent Progress on Primary Central Nervous System Lymphoma-From Bench to Bedside.

Primary central nervous system lymphoma (PCNSL) is a rare subtype of extra-nodal lymphoma. The high relapse rate of PCNSL remains a major challenge to the hematologists, even though patients exhibit high sensitivity to the methotrexate-based chemotherapeutic regimens. Recently, the advent of Bruton's tyrosine kinase inhibitor (BTKi) and CAR T treatment has made more treatment options available to a proportion of patients. However, whether BTKi monotherapy should be given alone or in combination with conventional chemotherapy is still a clinical question. The status of CAR T therapy for PCNSLs also needs to be elucidated. In this review, we summarized the latest progress on the epidemiology, pathology, clinical manifestation, diagnosis, and treatment options for PCNSLs.

Research Development on Anti-Microbial and Antioxidant Properties of Camel Milk and Its Role as an Anti-Cancer and Anti-Hepatitis Agent.

Camel milk is a rich source of vitamin C, lactic acid bacteria (LAB), beta-caseins and milk whey proteins, including lactoferrin, lysozyme, lactoperoxidase, alpha-lactalbumin and immunoglobulin. The lactoferrin plays a key role in several physiological functions, such as conferring antioxidant, anti-microbial and anti-inflammatory functions in cells. Similarly, the camel milk alpha-lactalbumin has shown greater antioxidative activity because of its higher antioxidant amino acid residues. The antioxidant properties of camel milk have also been ascribed to the structural conformation of its beta-caseins. Upon hydrolysis, the beta-caseins lead to some bioactive peptides having antioxidant activities. Consequently, the vitamin C in camel milk has a significant antioxidant effect and can be used as a source of vitamin C when the climate is harsh. Furthermore, the lysozyme and immunoglobulins in camel milk have anti-microbial and immune regulatory properties. The LAB isolated from camel milk have a protective role against both Gram-positive and -negative bacteria. Moreover, the LAB can be used as a probiotic and may restore the oxidative status caused by various pathogenic bacterial infections. Various diseases such as cancer and hepatitis have been associated with oxidative stress. Camel milk could increase antiproliferative effects and regulate antioxidant genes during cancer and hepatitis, hence ameliorating oxidative stress. In the current review, we have illustrated the anti-microbial and antioxidant properties of camel milk in detail. In addition, the anti-cancer and anti-hepatitis properties of camel milk have also been discussed.

Targeting chemokines for acute lymphoblastic leukemia therapy.

Acute lymphoblastic leukemia (ALL) is a hematological malignancy characterized by the malignant clonal expansion of lymphoid hematopoietic precursors. It is regulated by various signaling molecules such as cytokines and adhesion molecules in its microenvironment. Chemokines are chemotactic cytokines that regulate migration, positioning and interactions of cells. Many chemokine axes such as CXCL12/CXCR4 and CCL25/CCR9 have been proved to play important roles in leukemia microenvironment and further affect ALL outcomes. In this review, we summarize the chemokines that are involved in ALL progression and elaborate on their roles and mechanisms in leukemia cell proliferation, infiltration, drug resistance and disease relapse. We also discuss the potential of targeting chemokine axes for ALL treatments, since many related inhibitors have shown promising efficacy in preclinical trials, and some of them have entered clinical trials.

CLEC3B as a potential diagnostic and prognostic biomarker in lung cancer and association with the immune microenvironment.

BACKGROUND: Lung cancer is the leading cause of cancer-related mortality globally. Discovering effective biomarkers for early diagnosis and prognosis is important to reduce the mortality rate and ensure efficient therapy for lung cancer patients. C-type lectin domain family 3 member B (CLEC3B) has been reported in various cancers, but its correlation with lung cancer remains elusive. METHODS: The GEO, TCGA and Oncomine databases were analyzed to examine the expression of CLEC3B in lung cancer. The CLEC3B mRNA levels in 15 patient tissue samples were detected by real-time PCR and the CLEC3B protein levels in 34 patient tissue samples were detected by immunohistochemistry. A Chi-square test was performed to analyze the correlation of CLEC3B expression and clinicopathological factors. The diagnostic value of CLEC3B was revealed by receiver operating characteristic (ROC) curves. Univariate and multivariate Cox proportional hazards regression models and Kaplan-Meier plots were used to evaluate the prognostic value of CLEC3B in lung cancer. The TIMER database was used to evaluate the correlation of CLEC3B and immune infiltration. Gene set enrichment analysis revealed tumor-associated biological processes related to CLEC3B. RESULTS: CLEC3B is significantly downregulated in lung cancer patients compared with nontumor controls according to database analysis and patient tissue sample detection (p < 0.001). Specifically, CLEC3B is significantly downregulated in stage IA lung cancer patients (p < 0.001) and has a high diagnostic accuracy (area under the receiver operating characteristic curve > 0.9). Moreover, low expression of CLEC3B is related to poor progression-free survival (HR = 0.60, 95% CI 0.49-0.74, p = 8.3e-07) and overall survival (HR = 0.66, 95% CI 0.58-0.75, p = 2.1e-10), indicating it as a risk factor for lung cancer. Multivariate analysis value showed that low expression of CLEC3B may be an independent risk factor for disease-free survival in lung cancer patients (HR = 0.655, 95% CI 0.430-0.996, Cox p = 0.048). In addition, we also investigated the potential role of CLEC3B in tumor-immune interactions and found that CLEC3B might be associated with the immune infiltration and immune activation of lung cancer, especially in squamous cell carcinoma. CONCLUSIONS: Our findings indicate that CLEC3B expression is downregulated in lung cancer and reveal the diagnostic and prognostic potential of CLEC3B in lung cancer and its potential as an immune-related therapeutic target in lung cancer.

Nicotinamide increases the sensitivity of chronic myeloid leukemia cells to doxorubicin via the inhibition of SIRT1.

The NAD-dependent deacetylase Sirtuin 1 (SIRT1) plays a vital role in leukemogenesis. Nicotinamide (NAM) is the principal NAD+ precursor and a noncompetitive inhibitor of SIRT1. In our study, we showed that NAM enhanced the sensitivity of chronic myeloid leukemia (CML) to doxorubicin (DOX) via SIRT1. We found that SIRT1 high expression in CML patients was associated with disease progression and drug resistance. Exogenous NAM efficiently repressed the deacetylation activity of SIRT1 and induced the apoptosis of DOX-resistant K562 cells (K562R) in a dose-dependent manner. Notably, the combination of NAM and DOX significantly inhibited tumor cell proliferation and induced cell apoptosis. The knockdown of SIRT1 in K562R cells enhanced NAM+DOX-induced apoptosis. SIRT1 rescue in K562R reduced the NAM+DOX-induced apoptosis. Mechanistically, the combinatory treatment significantly increased the cleavage of caspase-3 and PARP in K562R in vitro and in vivo. These results suggest the potential role of NAM in increasing the sensitivity of CML to DOX via the inhibition of SIRT1.

Emerging Role of Myeloid-derived Suppressor Cells in the Biology of Transplantation Tolerance.

Myeloid-derived suppressor cells (MDSCs), a heterogeneous population of myeloid cells, are characterized by their immunosuppressive abilities through the secretion of various cytokines such as inducible nitric oxide synthase, nitric oxide, reactive oxygen species, transforming growth factor-ß, and arginase-1. Accumulating evidence highlights its potential role in maintaining immune tolerance in solid organ and hematopoietic stem cell transplantation. Mechanistically, MDSCs-induced transplant tolerance is mainly dependent on direct suppression of allogeneic reaction or strengthened cross-talk between MDSCs and Treg or NKT cells. Adopted transfer of in vitro- or in vivo-induced MDSCs by special drugs therefore becomes a potential strategy for maintaining transplantation tolerance. In this review, we will summarize the previously published data about the role of MDSCs in the biology of transplantation tolerance and gain insights into the possible molecular mechanism governing this process.