Discovery medicine最新文献

{"title":"Characterization of Metronidazole, Clarithromycin and Amoxicillin Resistance Genes in <i>Helicobacter pylori</i> Isolated from Gastroenteritis Patients.","authors":"Somaid Iqbal, Waheed Ullah, Syed Faheem Shah, Aisha Gul, Abdul Basit","doi":"10.24976/Discov.Med.202436188.171","DOIUrl":"https://doi.org/10.24976/Discov.Med.202436188.171","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;&lt;i&gt;Helicobacter pylori&lt;/i&gt; (&lt;i&gt;H. pylori&lt;/i&gt;)is a Gram-negative, microaerophilic, and spiral shape bacterium that resides inside the human stomach. The human stomach serves as its primary reservoir. Complaints about stomach complication due to &lt;i&gt;H. pylori&lt;/i&gt; infections are reported in the majority of populations around the globe. Chronic gastritis and intestinal metaplasia of the gastric mucosa are major complications of a long-term &lt;i&gt;H. pylori&lt;/i&gt; infections that can lead to gastric cancer in severe cases. This study aims to characterize &lt;i&gt;H. pylori&lt;/i&gt; isolates from gastroenteritis patients and to determine the resistance of &lt;i&gt;H. pylori&lt;/i&gt; to various antibiotics.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;In the current study, a total of (n = 80) gastric biopsy samples were randomly collected from gastroenteritis patients in brain-heart infusion broth. These were inoculated on Columbia blood agar supplemented with &lt;i&gt;Helicobacter pylori&lt;/i&gt; selective supplement (DENT). After culturing, Microscopy and biochemical tests were performed. The susceptibility profile of &lt;i&gt;H. pylori&lt;/i&gt; isolates was evaluated using the Kirby Bauer disk diffusion method. On the basis of the drug resistance profile, a total of (n = 20) isolates including (n = 10) from females and (n = 10) from males were selected for the detection and characterization of resistant genes. After confirmation of &lt;i&gt;H. pylori&lt;/i&gt; using &lt;i&gt;16s rRNA&lt;/i&gt;, polymerase chain reaction (PCR) was done for the detection of resistance genes including Metronidazole resistance (&lt;i&gt;rdxA&lt;/i&gt; gene), Clarithromycin resistance (&lt;i&gt;23s rRNA&lt;/i&gt; gene) and Amoxicillin resistance (Penicillin-binding protein A1 (&lt;i&gt;pbpA1&lt;/i&gt;) gene).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;In a total of (n = 80) samples, &lt;i&gt;H. pylori&lt;/i&gt; was isolated from 72.5% (n = 58) samples. Among the positive patients, there were 62% (n = 36) of female positive patients while in males, its ratio was 38% (n = 22). It was more common in the age between 30-50 years 55.17% (n = 32). It has shown the highest resistance towards Metronidazole 90% (n = 52), and the lowest toward Levofloxacin 65% (n = 38). Metronidazole resistance gene (&lt;i&gt;rdxA&lt;/i&gt; gene) was detected in (n = 13) isolates including (n = 9) isolates from females and (n = 4) from males. In the case of, the Clarithromycin resistance gene (&lt;i&gt;23s rRNA&lt;/i&gt;) (n = 10) was positive for &lt;i&gt;H. pylori&lt;/i&gt; including (n = 6) isolates from females and (n = 7) were positive for Amoxicillin (&lt;i&gt;pbpA1&lt;/i&gt; gene) including (n = 2) in female and (n = 5) from male patients.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;This study highlights the increasing incidence of &lt;i&gt;H. pylori&lt;/i&gt; infections in both male and female patients. It also revealed the current status of antibiotic resistance and its resistance genes in patients facing gastrointestinal issues. Continuous surveillance of resistant clones will help in formulating strategies that can help in combating of resistant clone. It will also help","PeriodicalId":93980,"journal":{"name":"Discovery medicine","volume":"36 188","pages":"1848-1857"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"METTL3 Regulates the Translation of Oncogene Myc through m⁶A Modification and Promotes the Occurrence and Development of Cervical Cancer.","authors":"Yanyan Ma, Hongyan Shi, Wei Zheng","doi":"10.24976/Discov.Med.202436188.176","DOIUrl":"10.24976/Discov.Med.202436188.176","url":null,"abstract":"<p><strong>Background: </strong>Cervical cancer (CC) is one of the major types of gynecological cancer, with a high global incidence and mortality rate. Methyltransferase-like 3 (METTL3), a key constituent of methyltransferase, plays a crucial role in various biological processes. Still, only a rare report has been made on its involvement in the progression of CC. Therefore, this study aims to investigate the impact of METTL3 in CC and its molecular mechanisms.</p><p><strong>Methods: </strong>Gene expression datasets about CC were obtained from the Gene Expression Omnibus (GEO) database, and the expression of <i>METTL3</i> and <i>Myc</i> was analyzed. Cell viability was detected after <i>METTL3</i> knockdown in HeLa and SiHa cells, followed by cell counting Kit-8 (CCK-8) assays. The relative expression of <i>METTL3</i> and <i>Myc</i> was detected via real-time quantitative PCR (qPCR) assays, and the protein expression was determined using Western blot. Meanwhile, cell invasion and migration capabilities were assessed utilizing transwell assays, and cell proliferation was detected using the EdU experiment. Furthermore, RNA methylation immunoprecipitation-qPCR detection was performed to determine the expression of <i>Myc</i> after N⁶-methyladenosine (m⁶A) modification.</p><p><strong>Results: </strong>Analysis of the GEO database indicated elevated expression of METTL3 and Myc in CC tissues. Patients with high METTL3 expression had shorter disease-free survival, and patients with high Myc expression had shorter overall survival. Following the knockdown of <i>METTL3</i>, there was a significant reduction in the viability, proliferation, invasion, and migration abilities of HeLa and SiHa cells. Besides, the expression of <i>METTL3</i> and <i>Myc</i> mRNAs and proteins was greatly reduced. The level of m⁶A <i>Myc</i> decreased significantly after <i>METTL3</i> knockdown.</p><p><strong>Conclusions: </strong><i>METTL3</i> plays an important role in regulating cervical cancer cells. <i>METTL3</i> promotes CC development through m⁶A modification to regulate the expression of the oncogene <i>Myc</i>.</p>","PeriodicalId":93980,"journal":{"name":"Discovery medicine","volume":"36 188","pages":"1902-1910"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142335003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Comparison between Demyelinating and Omicron Variant Infection-Associated Optic Neuritis.","authors":"Jing Zhang, Lian Wang, Chunli Chen, Haitao Ren, Miao Jin, Hongjuan Liu, Bentao Yang, Zhiqin Huang, Libin Jiang, Fred Kuanfu Chen","doi":"10.24976/Discov.Med.202436188.175","DOIUrl":"https://doi.org/10.24976/Discov.Med.202436188.175","url":null,"abstract":"<p><strong>Background: </strong>The connection between viral infection and the onset of demyelination has garnered considerable attention. Omicron, the most recent prevalent strain of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has raised concerns. Optic neuritis (ON) associated with Omicron infection and spontaneous demyelinating ON may manifest distinct disease progressions. This study aims to contrast the features of these two distinct etiologies of ON.</p><p><strong>Methods: </strong>This case-control study comprised fifteen patients (21 eyes) diagnosed with Omicron infection-related ON and fifteen patients (24 eyes) with demyelinating ON serving as the control group. Clinical characteristics, cerebrospinal fluid (CSF) analysis, treatment protocols, and outcomes were compared between the two groups.</p><p><strong>Results: </strong>The Omicron-infected group exhibited a higher incidence of pain upon ocular movement (<i>p</i> = 0.023) and peripapillary hemorrhages (<i>p</i> = 0.046). In CSF analysis, there was an elevation in white cell counts (WCCs) (<i>p</i> = 0.004), with lymphocytes being the predominant cell type in the Omicron-related ON group. However, oligoclonal bands (OCBs), indicative of intrathecal synthesis, were significantly lower and lagged behind those of the demyelinating ON group (<i>p</i> = 0.021). SARS-CoV-2 RNA was not directly detected in the CSF of the Omicron-related ON group, and the degree of WCC elevation was closely linked with peripapillary hemorrhages (odds ratio = 0.029, <i>p</i> = 0.02). Additionally, the Omicron-related ON group displayed more pronounced ganglion cell loss following 3-month treatment (<i>p</i> = 0.02).</p><p><strong>Conclusion: </strong>Omicron-related ON is distinguished by more pronounced clinical symptoms and distinct CSF characteristics compared to spontaneous demyelinating ON. The absence of viral RNA sequence in the CSF of Omicron-associated ON supports the use of steroid monotherapy; however, varying treatment options and prognoses should be considered for these two types of ON.</p>","PeriodicalId":93980,"journal":{"name":"Discovery medicine","volume":"36 188","pages":"1891-1901"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of Microbleeds on Susceptibility-Weighted Imaging with Ferroptosis and Prognosis in Rabbits with Spinal Cord Injury.","authors":"Xing-Zhen Liu, Bo-Cheng Wang, Kang-Ping Shen, Wen-Jie Jin, Jie Zhao","doi":"10.24976/Discov.Med.202436188.173","DOIUrl":"https://doi.org/10.24976/Discov.Med.202436188.173","url":null,"abstract":"<p><strong>Background: </strong>Susceptibility-weighted imaging (SWI) is a common imaging technique used to identify cerebral microbleeds. Given that spinal cord injury (SCI) often creates an environment that favors ferroptosis, a type of cell death driven by iron, this study aimed to explore the relationship between microbleeds on SWI and ferroptosis, and explore the effect of deferoxamine on SCI.</p><p><strong>Methods: </strong>Thirty-six rabbits were divided into three groups: sham, SCI, and SCI with deferoxamine (DFO, a ferroptosis inhibitor) treatment (SCI+DFO). Following 48 hours of SCI modeling, the rabbits underwent magnetic resonance imaging (MRI) and SWI examinations. Ferroptosis markers and spinal cord tissue morphology were examined, and the modified Tarlov's score was used to assess neurological function.</p><p><strong>Results: </strong>SWI analysis revealed that rabbits in the SCI group exhibited lower signal intensities and larger microbleed areas compared to the those in the SCI+DFO group (<i>p</i> < 0.05). The SCI+DFO group demonstrated significantly decreased iron and malondialdehyde (MDA) levels, coupled with increased glutathione (GSH) and glutathione peroxidase 4 (GPX4) levels, along with attenuated ferroptosis (<i>p</i> < 0.05). This group also displayed greater Neuronal Nuclei (NeuN) expression, Tarlov's scores, and neurological recovery rates (all <i>p</i> < 0.05). A significant positive correlation was found between the microbleed area and iron content (r = 0.59, <i>p</i> = 0.04), MDA (r = 0.75, <i>p</i> = 0.01), and mitochondrial damage (r = 0.90, <i>p</i> < 0.01). Conversely, a negative correlation was established between the microbleed area and GPX4 levels (r = -0.87, <i>p</i> < 0.01), as well as neurological function recovery (r = -0.62, <i>p</i> = 0.03).</p><p><strong>Conclusion: </strong>The extent of microbleeds on SWI following SCI is closely correlated with ferroptosis, and the inhibition of ferroptosis could improve neurologic function. These findings suggest that the area of microbleeds on SWI could potentially serve as a predictive marker for ferroptosis in spinal cord injury.</p>","PeriodicalId":93980,"journal":{"name":"Discovery medicine","volume":"36 188","pages":"1869-1879"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Berberine Alleviates Sevoflurane Anesthesia-Induced Cognitive Dysfunction in Neonatal Mice via Regulating CREB1.","authors":"Huajuan Wang, Wangsheng Wu, Qunyan Zheng, Fangyan Yu, Haitao Zhang, Gongmin Yu, Li Huang","doi":"10.24976/Discov.Med.202436188.174","DOIUrl":"10.24976/Discov.Med.202436188.174","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Sevoflurane has been shown to stimulate neurotoxicity and lead to cognitive impairment. Berberine is known for its role in regulating nervous system diseases, including cognitive dysfunction. This study aimed to investigate the effects of berberine on cognitive dysfunction induced by sevoflurane anesthesia and its potential mechanisms.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;In the &lt;i&gt;in vivo&lt;/i&gt; study, neonatal mice were subjected to sevoflurane anesthesia to induce cognitive dysfunction. The cognitive function of the neonatal mice was evaluated using the Morris water maze test, open field test, and tail suspension test. Enzyme-linked immunosorbent assay (ELISA) was utilized to assess the levels of inflammatory factors. Immunohistochemistry (IHC) was conducted to detect ionized calcium-binding adaptor molecule 1 (IBA-1)-positive cells and cleaved caspase-3-positive cells in the hippocampus of the neonatal mice. Western blotting was used to measure the levels of cyclic adenosine monophosphate (cAMP) response element-binding protein 1 (CREB1) in hippocampal tissues and neurons. Hippocampal neurons were isolated from the hippocampus of neonatal mice. These neurons were treated with berberine or subjected to cell transfection. The cell counting kit-8 (CCK-8) assay and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay were conducted to measure cell viability and apoptosis of hippocampal neurons &lt;i&gt;in vitro&lt;/i&gt;.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Berberine significantly attenuated sevoflurane-induced cognitive impairment and inflammation in neonatal mice (&lt;i&gt;p&lt;/i&gt; &lt; 0.05 or &lt;i&gt;p&lt;/i&gt; &lt; 0.01). Additionally, berberine reduced sevoflurane-triggered neuronal apoptosis in the hippocampus of neonatal mice (&lt;i&gt;p&lt;/i&gt; &lt; 0.01). Sevoflurane markedly decreased CREB1 expression in the hippocampus of neonatal mice (&lt;i&gt;p&lt;/i&gt; &lt; 0.01), which was elevated by berberine treatment (&lt;i&gt;p&lt;/i&gt; &lt; 0.01). Mechanistically, sevoflurane significantly suppressed cell viability and promoted cell apoptosis of hippocampal neurons (&lt;i&gt;p&lt;/i&gt; &lt; 0.0001 or &lt;i&gt;p&lt;/i&gt; &lt; 0.01), which were mitigated by berberine (&lt;i&gt;p&lt;/i&gt; &lt; 0.05, &lt;i&gt;p&lt;/i&gt; &lt; 0.01, or &lt;i&gt;p&lt;/i&gt; &lt; 0.001). Furthermore, berberine significantly elevated CREB1 expression in sevoflurane-treated hippocampal neurons (&lt;i&gt;p&lt;/i&gt; &lt; 0.01). The beneficial effects of berberine on cell viability and apoptosis in sevoflurane-treated hippocampal neurons were blocked by CREB1 depletion (&lt;i&gt;p&lt;/i&gt; &lt; 0.001).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Our results demonstrated that CREB1 was significantly decreased in the hippocampus of sevoflurane-treated neonatal mice &lt;i&gt;in vivo&lt;/i&gt; and in sevoflurane-treated hippocampal neurons &lt;i&gt;in vitro&lt;/i&gt;. This decrease was mitigated by berberine treatment. Moreover, berberine improved sevoflurane anesthesia-induced cognitive impairment in neonatal mice by attenuating neuronal inflammation and apoptosis &lt;i&gt;in vivo&lt;/i&gt;. The inhibitory effects of berberine on sevoflurane-induced","PeriodicalId":93980,"journal":{"name":"Discovery medicine","volume":"36 188","pages":"1880-1890"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Impact of Dibutyl Phthalate on Insulin Signaling in Human Skeletal Muscle Cells.","authors":"Dan Shan, Yan Chen, Kunyan Zhou","doi":"10.24976/Discov.Med.202436188.167","DOIUrl":"10.24976/Discov.Med.202436188.167","url":null,"abstract":"<p><strong>Background: </strong>In China, the environmental concern of Dibutyl Phthalate (DBP) exposure significantly endangers human health by inducing insulin resistance (IR). Skeletal muscle tissue plays a critical role in this process. However, the precise molecular mechanisms through which DBP interferes with the insulin signaling pathway remain to be fully elucidated. This study aims to explore the molecular mechanisms by which DBP induces IR in skeletal muscle, focusing on the phosphatidylinositol 3-kinase (PI3K)-serine/threonine kinase (AKT)-glucose transporter 4 (GLUT4) signaling pathway.</p><p><strong>Methods: </strong>To investigate the molecular mechanisms underlying DBP-induced IR, an experimental study was established on a human skeletal muscle cell line (HSkMC). Expression levels of mRNA and proteins associated with key signaling genes within the insulin receptor (INSR)-insulin receptor substrate (IRS)-PI3K-AKT-GLUT4 pathway were assessed using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot techniques. Additionally, this study explored the effects of DBP alone and in combination with a PI3K inhibitor (BKM120) or phosphatase and tensin homolog (PTEN) overexpression lentivirus on these signaling components.</p><p><strong>Results: </strong>Results from this study demonstrated that DBP exposure significantly decreased mRNA levels of <i>INSR</i>, <i>IRS1</i>, <i>PI3K</i>, <i>AKT2</i>, and <i>GLUT4</i> in HSkMC cells compared to untreated control cells. This reduction was exacerbated when DBP was combined with BKM120 or PTEN overexpression lentivirus, suggesting a synergistic effect. Furthermore, DBP treatment reduced the expression and phosphorylation of AKT2, indicating a disruption in the insulin signaling pathway.</p><p><strong>Conclusions: </strong>This study elucidates a molecular mechanism by which DBP induces IR in skeletal muscle cells, primarily through the deregulation of the PI3K-dependent insulin signaling pathway. These insights enhance comprehension of the pathophysiological changes associated with IR caused by environmental pollutants like DBP, potentially guiding future strategies for prevention and intervention.</p>","PeriodicalId":93980,"journal":{"name":"Discovery medicine","volume":"36 188","pages":"1811-1818"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142335008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between <i>DEFB1</i> rs11362 and Caries Susceptibility in Permanent Dentition: A Cross Sectional Study.","authors":"Qiulin Liu, Li Liu, Shaoyong Chen, Xueting Yu, Shuang Chen, Shiqi Cheng, Xiaojuan Zeng","doi":"10.24976/Discov.Med.202436188.170","DOIUrl":"https://doi.org/10.24976/Discov.Med.202436188.170","url":null,"abstract":"<p><strong>Background: </strong>Dental caries is a multifactorial chronic bacterial infectious disease. Variations in the predisposition of the general population to dental cavities suggest that genetic and immunological factors play significant roles in its pathogenesis. This study aims to explore the impact of the Beta-Defensin 1 (<i>DEFB1</i>) rs11362 polymorphism on caries susceptibility in permanent dentition among the Bai Kuyao and Zhuang ethnic groups in China.</p><p><strong>Methods: </strong>A sample of 754 adolescents aged 12-15 was randomly selected from primary and junior high schools in Nandan County, Guangxi, China. All adolescents underwent clinical examinations, and DNA samples were collected. The genotype of <i>DEFB1</i> rs11362 was determined using single nucleotide polymorphism (SNP) typing. The concentration of human β Defensin 1 (hBD-1) protein in saliva was measured using a double-antibody sandwich enzyme-linked immunosorbent assay (ELISA).</p><p><strong>Results: </strong>The distribution of the <i>DEFB1</i> rs11362 T allele was lower in the Bai Kuyao group compared to the Zhuang group. The disparity in the rs11362 genotype was statistically significant in the superficial dentin caries subgroup of the Bai Kuyao population (<i>p</i> = 0.017). Following adjustment for all potential confounding variables, the analysis revealed a heightened risk of superficial dental caries among CT genotype carriers in the Bai Kuyao population under a co-dominant model (odds ratios (OR) = 2.70; 95% confidence intervals (CI) [1.35-5.44]; <i>p</i> = 0.005), and an increased risk among CC genotype carriers in the Bai Kuyao population under a dominant model (OR = 2.35; 95% CI [1.18-4.67]; <i>p</i> = 0.015). A significant difference (<i>p</i> < 0.05) was noted in the distribution of rs11362 genotypes and salivary hBD-1 levels among the Bai Kuyao group. Salivary hBD-1 levels were notably higher in the CC genotype group (4.12 ± 2.07 ng/mL) compared to both the CT (2.77 ± 1.62 ng/mL) and TT genotype groups (2.32 ± 0.98 ng/mL).</p><p><strong>Conclusion: </strong>The <i>DEFB1</i> rs11362 polymorphism showed an association with caries susceptibility in permanent teeth and influenced hBD-1 protein expression in saliva. Consequently, the <i>DEFB1</i> polymorphism likely represents a concealed risk factor for caries.</p>","PeriodicalId":93980,"journal":{"name":"Discovery medicine","volume":"36 188","pages":"1840-1847"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PCGF2 Acts as an Oncogenic Driver in Colon Cancer through the Upregulation of CENPE.","authors":"Qingwei Luo, Xiaoli Chen, Jun Tang, Wei Yan, Zhihong Li","doi":"10.24976/Discov.Med.202436188.166","DOIUrl":"https://doi.org/10.24976/Discov.Med.202436188.166","url":null,"abstract":"<p><strong>Background: </strong>Colon cancer (CC) is a highly prevalent malignancy that contributes significantly to global morbidity and mortality. The polycomb group ring finger 2 (PCGF2) has been identified as a relevant factor influencing the outcomes of CC. At the same time, the centromere-associated protein E (CENPE) is implicated in promoting carcinogenesis and adversely affecting the survival of tumor patients. The primary objective of this study was to elucidate the precise impact of PCGF2 on CC and unravel the underlying mechanisms associated with CENPE.</p><p><strong>Methods: </strong>Human normal colon epithelial cells and CC cells were utilized to investigate the differential expression of PCGF2 and CENPE. CC cell line LOVO was exploited and transfected for PCGF2 regulation. Subsequently, cell viability and proliferation were assessed using the cell counting kit 8 (CCK-8) and colony forming assay. Cell viability and proliferation were assessed using the terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) assay, while cell migration and invasion capabilities were determined using the transwell assay, and mRNA levels of cell cycle-related genes were measured for evaluating cell cycle activation. In addition, mice were used for <i>in vivo</i> experiments to investigate the progression of CC cells with different levels of PCGF2. Moreover, GSK-923295 was used to inhibit CENPE, followed by the evaluation of cell progression.</p><p><strong>Results: </strong>PCGF2 and CENPE were upregulated in CC cell lines (<i>p</i> < 0.001), and upregulation/downregulation of PCGF2 led to the upregulation and downregulation of CENPE (<i>p</i> < 0.001). The upregulation/downregulation of PCGF2 led to an increase/decrease in viability, proliferation, migration, and invasion while suppressing/enhancing apoptosis in LOVO cells (<i>p</i> < 0.001), promoting cell progression. The tumor progression of LOVO cells with PCGF2 knockdown was slower (<i>p</i> < 0.001). The PCGF2-promoting LOVO cell progression was disrupted when CENPE was inhibited, presented by the reversely decreased viability, proliferation, migration, invasion, and cell cycle activation, and increased apoptosis (<i>p</i> < 0.001).</p><p><strong>Conclusion: </strong>PCGF2 promotes CC cell progression by upregulating CENPE, providing PCGF2 inhibition and CENPE inhibition as potential therapeutic targets for treating CC.</p>","PeriodicalId":93980,"journal":{"name":"Discovery medicine","volume":"36 188","pages":"1800-1810"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142335005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current and Emerging Immunotherapies for Systemic AL Amyloidosis.","authors":"Valeria Moreno, Ludovic Saba, Sara Tama-Shekan, Chakra P Chaulagain","doi":"10.24976/Discov.Med.202436188.162","DOIUrl":"https://doi.org/10.24976/Discov.Med.202436188.162","url":null,"abstract":"<p><p>Systemic light-chain (AL) amyloidosis is a rare and complex clonal plasma cell neoplasm characterized by the production of misfolded and unstable immunoglobulin light-chains leading to multisystem amyloid deposition, which progresses to organ dysfunction and eventual failure. The importance and urgency of AL amyloidosis depends on its potential to induce significant organ impairment, progressive course, risk of life-threatening complications, and the limited treatment options available. Treatment options and prognosis depend on the number and severity of organ involvement at the time of diagnosis with cardiac involvement carrying the worst outcomes. The treatments aim to target eliminating the underlying clonal plasma cell neoplasm and prevent the production and deposition of amyloid precursor immunoglobulin light-chain protein in the affected vital organs. Strategies for treating systemic AL amyloidosis have incorporated anti-plasma cell therapies approved in the management of multiple myeloma due to their shared cellular derivation. Quadruplet therapy of cyclophosphamide, bortezomib, dexamethasone and daratumumab (DaraCyborD) is the currently approved first-line induction therapy for systemic AL amyloidosis. Some patients need upfront autologous hematopoietic stem cell transplantation (HSCT) after high-dose melphalan conditioning particularly if DaraCyborD is not able to achieve complete hematologic response (CHR). Additionally, a promising treatment option involves disassembling amyloid deposits from the vital organs using monoclonal antibodies such as CAEL 101 or Birtamimab with the expectation of restoring damaged tissues of the vital organs affected thereby improving or reversing patients' symptoms. Both CAEL 101 and Birtamimab are currently being tested in phase 3 clinical trials for systemic AL amyloidosis patients with advanced cardiac involvement. This comprehensive review provides an up-to-date overview of AL amyloidosis therapy, with a particular focus on recent advances and future directions of immunotherapeutic strategies.</p>","PeriodicalId":93980,"journal":{"name":"Discovery medicine","volume":"36 188","pages":"1761-1771"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>CCT2</i> Regulates <i>ZEB1</i>-Induced EMT Gene Transcription to Promote the Metastasis and Tumorigenesis of Papillary Thyroid Carcinoma.","authors":"Weiping Liu, Renzhi Lin, Chumeng Zhu, Yuxingzi Chen, Qiangang Gao, Jijun Zhong","doi":"10.24976/Discov.Med.202436188.168","DOIUrl":"10.24976/Discov.Med.202436188.168","url":null,"abstract":"<p><strong>Background: </strong>Papillary thyroid carcinoma (PTC) is the most common malignant tumor of the thyroid, and its invasiveness and metastatic ability are closely related to patient prognosis. Chaperonin containing TCP1 subunit 2 (CCT2) is an important component of the molecular chaperone protein complex and has been shown to regulate cell proliferation and migration in various tumors. Epithelial-mesenchymal transition (EMT) is a critical process in tumor metastasis, and Zinc Finger E-Box Binding Homeobox 1 (<i>ZEB1</i>) is a core transcription factor that regulates EMT. This study aims to explore how <i>CCT2</i> induces EMT gene transcription through <i>ZEB1</i>, thereby promoting the metastasis and tumorigenesis of PTC.</p><p><strong>Methods: </strong>CCT2 in PTC tissues was analyzed using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot. siRNA and overexpression vectors were used to silence and overexpress <i>CCT2</i>, respectively, and the effects on PTC cell migration, invasion, proliferation, and apoptosis were observed. Rescue experiments were used to investigate the effect of <i>CCT2</i> on <i>ZEB1</i> and EMT-related genes. Cell apoptosis was detected by Terminal deoxynucleotidyl transferase dUTP Nick End Labeling (TUNEL) assay. Silencing <i>ZEB1</i> was used to verify its effect on the oncogenic activity of <i>CCT2</i>.</p><p><strong>Results: </strong><i>CCT2</i> was found to be highly expressed in PTC tissues (<i>p</i> < 0.01). In <i>in vitro</i> and <i>in vivo</i> experiments, silencing <i>CCT2</i> inhibited the migration and invasion of PTC cells and their metastasis, while overexpression of <i>CCT2</i> produced the opposite effect. Additionally, <i>CCT2</i> promoted PTC cell proliferation and inhibited apoptosis (<i>p</i> < 0.01). Mechanistic studies revealed that <i>CCT2</i> upregulated <i>ZEB1</i> expression (<i>p</i> < 0.01), thereby inducing EMT gene transcription (<i>p</i> < 0.01). Silencing <i>ZEB1</i> reduced the oncogenic effect of <i>CCT2</i>.</p><p><strong>Conclusion: </strong>This study first revealed the high expression of <i>CCT2</i> in PTC and its essential role in the migration, invasion, proliferation, and anti-apoptosis of tumor cells. <i>CCT2</i> promotes the metastasis and tumorigenesis of PTC by regulating <i>ZEB1</i> and EMT-related genes. These findings provide new potential targets for molecular targeted therapy of PTC and explore new directions for future clinical treatment strategies.</p>","PeriodicalId":93980,"journal":{"name":"Discovery medicine","volume":"36 188","pages":"1819-1830"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}