Cellular and molecular biology最新文献

Connective tissue growth factor (CTGF) and Caspase 8 (CASP8) have been implicated in cancer development and progression. Variants such as CASP8 rs3834129 (-652 6N I/D) and CTGF rs6918698 (-945 C>G) have been associated with several cancers, although their association is still debated between populations. This study investigates the possible association between the CASP8 rs3834129 and CTGF rs6918698 variants with  colorectal cancer (CRC) in Mexican patients. Genomic DNA was extracted from 250 CRC patients and 250 control subjects. The identification of CASP8 and CTGF variants was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. The association was determined by the odds ratio (OR) analysis and P values were adjusted by the Bonferroni correction. Patients carrying the D/D genotype for the CASP8 rs3834129 variant exhibited an increased susceptibility to CRC (P = 0.012). The D/D genotype was associated with older 50-year-old patients (P = 0.006). In addition, this same D/D genotype was associated with TNM II stage (P = 0.013) and rectal localization (P = 0.023). Additionally, patients carrying the G/G genotype for the CTGF rs6918698 variant showed a decreased susceptibility to CRC (P = 0.009), and in the sex stratification, this gene has protective role in males (P = 0.008). This same genotype was associated with decreased susceptibility to early TNM stages (I+II) (P = 0.023) and right-sided colon tumor localization (P = 0.002). There was no association between response to treatment and the variants analyzed. Our findings suggest that the CASP8 rs3834129 and CTGF rs6918698 variants have a significant impact on the development of CRC.

During the field visits in growing season of 2022 in Dammam Region of Saudi Arabia, begomovirus-like symptoms including leaf curling, leaf cupping, leaf distortion, vein thickening and reduced leaf size were observed in squash and cucumber fields. Twenty-five samples were collected from each crop and PCR amplification was done using general diagnostic begomovirus primers (AC-1048/AV-494 and Begomo I/Begomo II). The obtained results showed desired sized amplified DNA fragments (550 bp and 1.1 kb) according to the primer sites. Sequencing results were analyzed using BLAST and revealed the presence of three different bipartite begomoviruses which include Squash leaf curl virus (SqLCV) isolated from squash and cucmber, Watermelon chlorotic stunt virus (WmCSV) and Tomato leaf curl Palampur virus (ToLCPalV) isolated from squash. The highest nucleotide identity found was 99.4% with Egyptian SqLCV isolated from squash and the lowest similarity was 93.3% found with a USA isolate isolated from wheel cactus. Sequencing results of two isolates of WmCSV showed 100% sequence identity with each other, eight isolates from Palestine isolated from watermelon, two isolates from Mexico isolated from prickly pear cactus and Watermelon, one isolate from each Lebanon and Jordan isolated from melon and wild mustard respectively. The lowest identity (87%) was found with a Saudi Arabian isolate isolated from papaya. For ToLCPalV isolate showed the highest identity (100 %) with an already reported isolate of same virus from melon in Saudi Arabia and two isolates isolated from cucumber and cantaloupe in Iran. However, the lowest identity (95.3%) was found with an Indian isolate isolated from eggplant. This is the first investigation of complex viral disease caused by SqLCV, WmCSV and ToLCPalV on the basis of molecular characterization from squash and a SqLCV isolate from Cucumber in Saudi Arabia.

The current study was designed to investigate the effect of A. indica (Neem) leaf extracts (ethanolic and aqueous) in yeast-induced pyrexia and acetic acid-induced writhing in rat models to evaluate the antipyretic and analgesic biomarkers and its phytochemical screening with computational analysis. For the antipyretic activity model 60 albino rats (160-200g) of either sex were divided into 4 groups and all groups were injected with yeast to induce pyrexia. Out of 4 groups, first group (control) consisted of 6 rats, treated with normal saline, the second group (standard) comprised 6 rats, treated with paracetamol. Third and fourth experimental groups consisted of 48 rats, treated with A. indica leaf ethanolic and aqueous extracts at doses of (50, 100, 200 and 400mg/kg b.w). For analgesic activity group division was the same and all groups were injected with acetic acid to induce pain TNF-α and IL-6 levels were measured using ELISA kits after blood samples were taken and serums were separated. An acute toxicity study was performed. In molecular docking, nimbandiol and nimbolide were used as ligand molecules to target protein Tnf-α and IL-6. In both activities at the dose of 400mg/kg, group III showed significant inhibition (p<0.05). Biomarkers showed significant results at the dose of 400mg/kg. Phytochemical screening was performed to reveal the existence of various active constituents. In molecular docking, nimbandiol and nimbolide showed -5 and -5.3 binding energies respectively, as compared to the standard drug paracetamol with -4.2 binding energy to TNF-Alpha protein. Therefore, A. indica extracts can be used as a valuable drug for the treatment of pain and fever.

The incidence of melanoma, a highly aggressive skin cancer, continues to increase worldwide, particularly among populations with lighter skin tones. The diagnostic challenge of melanoma lies in the absence of a distinctive clinical presentation, as its characteristics vary based on anatomical location, growth type, and histopathology. The melanoma-associated antigen (MAGE) gene family is differentially expressed in various human cancers, including melanoma. In this study, we explored the association between human MAGEA2 (hMAGEA2) expression and melanoma. Using a human melanoma tissue array, we confirmed that hMAGEA2 expression was higher in melanoma and metastatic melanoma than in normal tissues. Additionally, we used SK-MEL-5 and SK-MEL-28 cell lines to investigate the cellular and molecular mechanisms underlying melanoma progression and invasiveness. In SK-MEL-5 and SK-MEL-28 cells, hMAGEA2 overexpression accelerated cell proliferation. Conversely, the knockdown of hMAEGA2 reduced cell proliferation, colony formation, and migration significantly and induced arrest at the G2/M phase of the cell cycle. With respect to the molecular mechanism, the knockdown of hMAGEA2 decreased the phosphorylation of Akt, JNK, and p38 MAPK. Additionally, hMAGEA2 knockdown reduced tumor formation significantly at the in vivo level. Collectively, the robust correlation between hMAGEA2 and melanoma metastasis supports the potential utility of hMAGEA2 as both a diagnostic marker and novel therapeutic target for patients with melanoma metastasis.

Substances released outside of the cells during cell necrosis are collectively called danger-associated molecular patterns (DAMPS) or alarmins. A pro-inflammatory cytokine, interleukin-1α (IL-1α) is known as a typical alarmin. IL-1α transmits signals by binding to IL-1 receptor 1 (IL-1R1), type I protein, expressed on the cell membrane of target cells, but detection of IL-1R1 at the protein and mRNA levels is difficult. Although the reasons are not elucidated, we attempted to add the HiBiT-tag to the N-terminus (N'-R1) or C-terminus (C'-R1) of IL-1R1 to examine whether the detection sensitivity can be augmented. Increase in detection sensitivity will allow the investigation of its function and subcellular localization much further. Using uterine cervical cancer-derived HeLa cells and its derivative CR-R1-4 cells lacking IL-1R1, C'-R1 was demonstrated to significantly increase the detection sensitivity of IL-1R1. Furthermore, the signal transduction function of neither N'-R1 nor C'-R1 was affected. Immunofluorescence cell staining revealed that wild-type IL-1R1 is mainly localized in the nucleus, whereas C'-R1 is localized both in the nucleus and the cytoplasm. The above results showed that adding a tag to the C-terminus of IL-1R1 increases detection sensitivity while maintaining its function. In the future, we would like to further investigate the relationship between changes in the intracellular localization of C'-R1 and increases in detection sensitivity.

Chronic periodontitis (CP) is distinguished by an inflammatory reaction and the presence of oxidative stress (OS), which has consequences for overall health. Interleukin-1β (IL-1β) and malondialdehyde (MDA) serve as markers of inflammation and OS, respectively. Analyzing the alterations in their reaction to periodontal therapy can provide valuable insights into the management and monitoring of CP progression. The current study aimed to evaluate the impact of non-surgical periodontal therapy (NST) on IL-1β and MDA levels in the serum and saliva of CP patients and explore their correlation with clinical periodontal indices post-therapy. There were 60 participants in this research, aged 33 to 50, equally split between thirty periodontally healthy controls and 30 patients with CP. Measures were taken of the clinical periodontal parameters, including the bleeding index, probing pocket depth, gingival index, and plaque index. Saliva and blood samples were collected for IL-1β and MDA analysis using ELISA and spectrophotometrically. CP patients received scaling and root planning (SRP) as part of phase I periodontal therapy, and after six weeks, we reevaluated clinical parameters and IL-1β and MDA levels. In CP patients, both saliva and serum IL-1β and MDA levels significantly increased alongside worsening clinical periodontal parameters compared with periodontally healthy individuals. phase I periodontal therapy led to a notable decrease in both saliva and serum IL-1β and MDA levels, accompanied by improvements in clinical parameters. Additionally, following six weeks of scale and root planning treatment, our data showed a strong positive relationship between salivary IL-1β and MDA levels with PPD and CAL. SRP therapy is effective in managing periodontal health, as evidenced by a significant decrease in clinical parameters and biomarker levels after treatment for CP patients. This suggests that salivary IL-1β and MDA may be useful biomarkers for indicating the severity of periodontal disease and the effectiveness of treatment.

Gout is a systemic disorder that occurs due to an accumulation of uric acid crystals in the tissues. The association between the Ketogenic diet and uric acid concentration has been poorly established. This study aims to evaluate and assess the association of Serum uric acid and other variables with ketogenic diet among Gout patients in comparison with Healthy control subjects. A case-control observational study. Subjects were grouped into Group I (Gout patients-103 individuals) and Group II (healthy Subjects-55 individuals). Parameters of Serum creatinine, blood urea, and uric acid were assessed for both groups. The study population included 51.3% of male and 48.7% of female participants, with an age range of 20-74, with a mean of 35.72±13.69 years old. Ketogenic and meat-rich diet as strong risk factors for Gout were higher among all case groups (45.6%) and (92.2%), respectively. The Pearson's correlation coefficient of serum uric acid with other variables showed that the relation between serum uric acid with age, and weight among gout patients was found to be a weakly positive correlation and statistically significant (r=0.24, P= 0.013), and (r=0.22, P=0.026) respectively. This prospective study confirms that a ketogenic diet and a diet rich in meat have been associated with an increased incidence of gout.  Indeed, results have shown that the ketogenic diet might have an increasing effect on serum uric acid. The frequencies of comorbidities have been constantly shown to be increased in gout.

The study objectives were to analyze catheter-associated bloodstream infection (CABSI) risk factors in chronic kidney disease on regular hemodialysis and identify the bacterial species responsible for this by molecular analysis. This research was conducted in Erbil Teaching Hospital-Dialysis Unit in Erbil City-Kurdistan Region-Iraq from January to June 2024. It has been performed on 100 hemodialysis samples from both males and females. The investigation showed that the prevalence of CABSI among hemodialysis patients was 44 (44%) out of 100 (100%). The highest percentage of patients were aged between 60-69 years (32%, OR= 0.9, 95%CI [0.1-2.4], P< 0.001) and also male (66%, OR=2.7, 95%CI [0.9-9.4], P< 0.032). Additionally, the patients with Diabetes Mellitus were 70%, (OR= 6.3, 95%CI [0.3-10.4], P< 0.031), and with hypertension was 92%, (OR= 3.1, 95%CI [0.21-5.4], P<0.02.  However, the dialysis duration of most patients was between 1-3 months (60%, OR=0.1, 95%CI [0.1-3.2], P<0.006) and the majority used two catheters (52%, OR= 0.6, 95%CI [0.1-3.2], P<0.012). The most common pathogens identified were Staphylococcus epidermis (44 cases, 100%), Pseudomonas aeruginosa (29 cases, 66%), and, Acinetobacter baumanni (24 cases, 55%). Thirteen bacterial species were recorded in the NCBI GenBank database. The phylogenetic tree demonstrated the distribution and relationship between these bacteria in hemodialysis patients. It showed that the bacterial species were closely related. To lower the risk of catheter-associated bloodstream infection, medical staff should actively develop countermeasures and gain a thorough understanding of the risk factors, which include age, diabetes, length of catheterization, and catheterization site.

The present study examined the functional activities of the human bone marrow mesenchymal stem cells (hBM-MSCs) under the effects of various concentrations of the inflammatory mediator interleukin 1 beta (IL-1β). The effects of IL-1β on the functional properties of hBM-MSCs were measured using functional assays (adhesion, proliferation, and migration). hBM-MSCs expressions of colony-stimulating factors 1 and 2 (CSF1, CSF2), C-C chemokine receptor type 2 (CCR2), C-X-C chemokine receptor type 1 and 3 (CXCL1, CXCL3), were examined using real-time polymerase chain reaction (RT‒PCR). The pro-inflammatory cytokine IL-1β did not disrupt hBM-MSCs adhesion, but it improved proliferation and migration only up to 50 ng/ml. However, in response to 100 ng/ml IL-1β, cell growth, proliferation, and migration were reduced significantly. The expression of CSF1, CCR2, CXCL3, and IL-1β genes increased with the increase in the concentration of IL-1β. CSF2 and CXCL1 gene expression increased in the 50ng/ml group compared with the 10ng/ml group to be higher than the control group in the 100ng/ml IL-1β group which might facilitate the differentiation, and homing of MSCs to the site of injury and augment their activities in the inflamed microenvironment. The study corroborates the advantages of prior stimulation of mesenchymal stem cells (MSCs) with the cytokine IL-1β, demonstrating an upregulation of key chemokines and cytokines. This upregulation potentially enhances MSCs' ability to differentiate and migrate to injury sites, while also augmenting their functional role within an inflamed microenvironment, thereby amplifying their therapeutic potential.

Breast cancer is the most common malignancy in women. Breast cancer, the second leading cause of cancer deaths, affects 2.1 million women each year and is estimated to have killed 627,000 women worldwide in 2018. Unfortunately, the age of onset of this cancer in our country IRAN is about 10 years lower than the global average and is close to 45 years. Chemotherapy is one of the basic treatments for cancer. Predicting the benefits of chemotherapy is challenging. Studies are now underway to use gene expression tests to pinpoint patients who are most likely to benefit from adjuvant chemotherapy. In the present study, the expression of two long non-coding RNAs TP53TG1 and PANDA in the blood of breast cancer patients before and after receiving chemotherapy compared with this amount in the blood of normal people using Real-Time RT PCR technique to find a meaningful relationship ¬ Compared statistically. Compared to normal samples, the expression level of TP53TG1 in the blood of patients was reduced. Although it was not statistically significant. Its expression also increased after receiving chemotherapy. Compared to normal samples, the expression of PANDA in the blood of patients was increased, which was statistically significant. Also, its expression decreased after receiving chemotherapy. These findings suggest that PANDA and TP53TG1 expression levels may be possible markers associated with tumorigenesis and may also be considered as possible indicators of response to chemotherapy.