The coronavirus SARS-CoV-2 is the causative agent of the ongoing severe acute respiratory disease pandemic COVID-19. Tissue and cellular tropism is one key to understanding the pathogenesis of ...SARS-CoV-2. We investigate the expression and subcellular localization of the SARS-CoV-2 receptor, angiotensin-converting enzyme 2 (ACE2), within the upper (nasal) and lower (pulmonary) respiratory tracts of human donors using a diverse panel of banked tissues. Here, we report our discovery that the ACE2 receptor protein robustly localizes within the motile cilia of airway epithelial cells, which likely represents the initial or early subcellular site of SARS-CoV-2 viral entry during host respiratory transmission. We further determine whether ciliary ACE2 expression in the upper airway is influenced by patient demographics, clinical characteristics, comorbidities, or medication use, and show the first mechanistic evidence that the use of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARBs) does not increase susceptibility to SARS-CoV-2 infection through enhancing the expression of ciliary ACE2 receptor. These findings are crucial to our understanding of the transmission of SARS-CoV-2 for prevention and control of this virulent pathogen.
This study aimed to investigate skin condition, quality of life, and psychological impact of breast cancer patients after radiation therapy. We designed and administered a questionnaire to breast ...cancer survivors for better understanding the skin sequelae after radiation therapy.
This study performed an anonymous online survey. Invitation join was posted in Facebook groups for Breast Cancer. Content of the questionnaire included basic information and a three-point scale on the degree of skin dryness, sweating, hotness sensation, itchy sensation, presence of pigment deposition, history of severe skin disorder, psychological impact, and quality of life after radiotherapy. Categorical variables were summarized using counts and percentages, and then Mantel-Haenszel chi-square tests, multiple correspondence analysis, Wald chi-square statistics, and logistic regression analyses were performed; P < 0.05 was considered statistically significant.
In total, 421 breast cancer survivors completed the questionnaire. Among them, 331 (78.62%) reported rarely sweating; 340 (80.76%) reported dry skin; 184 (43.71%) reported itchy skin in addition to dry skin; 336 (79.81%) had severe or mild skin color deposition; and 76 (18.05%) had eczema or contact dermatitis. Dry skin problems were caused by absent sweating and skin dryness in the irradiated skin area, post-RT severe skin disorders, and skin color deposition. Compared with patients sweating normally in the radiation field, patients with absent sweating and hotness sensation in the radiation field had a higher risk of depression.
This study showed that breast cancer patients after whole breast radiotherapy may experience skin dryness, hypersensitivity and hyper pigmentation in the irradiated skin area. These "radiation-irritated skin" lesions may induce depressive psychological status and impact the quality of life in breast cancer patients after whole breast radiotherapy.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Cisplatin resistance is a major clinical problem in the clinical management of oral squamous cell carcinoma (OSCC) patients. Resveratrol is a natural phytoestrogen with antitumor activities. Whether ...resveratrol can overcome cisplatin resistance and prevent metastasis in OSCC cells is not known. In this study, we first examined the anti‐metastatic capacity of resveratrol and then explored the underlying mechanisms using a cisplatin‐resistant human OSCC cell line (CAR). The results demonstrated that at a non‐toxic dose range (25 to 75 µM), 24‐hr treatment of resveratrol was able to suppress the migration and invasion capacities of CAR cells dose dependently. Interestingly, 50 µM resveratrol treatment could significantly down‐regulate the expression of the phosphorylated forms of ERK and p‐38, in addition to those of MMP‐2 and MMP‐9. At the same time, the expression levels of phosphorylated ERK together with those unphosphorylated forms of ERK, p38, and JNK were all insignificantly altered. In conclusion, the signaling cascade for resveratrol's suppression of cisplatin‐resistant human oral cancer CAR cells was revealed and summarized. Also the rapid effectiveness in suppressing metastatic behaviors of drug‐resistant oral cancer cells of non‐toxic resveratrol might extend its application to the drug‐resistant oral cancer treatment in the near future.
Practical applications
Based on the evidence we provided in the study, we have proposed a model recording the possible pathway for resveratrol inhibiting the metastasis of cisplatin‐resistant oral cancer cells. We suppose this signaling pathway may work in other cancer cell lines, and can be helpful in full understanding of the drug‐resistance
The current study provides the drug reposition evidence for resveratrol can inhibit the metastasis behaviors of cisplatin‐resistant oral cancer cells. This novel application is beneficial in not only clinical therapy for the oral cancer patients but also in translational medical science achievements.
The coronavirus disease 2019 (COVID‑19) outbreak, which has caused >46 millions confirmed infections and >1.2 million coronavirus related deaths, is one of the most devastating worldwide crises in ...recent years. Infection with COVID‑19 results in a fever, dry cough, general fatigue, respiratory symptoms, diarrhoea and a sore throat, similar to those of acute respiratory distress syndrome. The causative agent of COVID‑19, SARS‑CoV‑2, is a novel coronavirus strain. To date, remdesivir has been granted emergency use authorization for use in the management of infection. Additionally, several efficient diagnostic tools are being actively developed, and novel drugs and vaccines are being evaluated for their efficacy as therapeutic agents against COVID‑19, or in the prevention of infection. The present review highlights the prevalent clinical manifestations of COVID‑19, characterizes the SARS‑CoV‑2 viral genome sequence and life cycle, highlights the optimal methods for preventing viral transmission, and discusses possible molecular pharmacological mechanisms and approaches in the development of anti‑SARS‑CoV‑2 therapeutic agents. In addition, the use of traditional Chinese medicines for management of COVID‑19 is discussed. It is expected that novel anti‑viral agents, vaccines or an effective combination therapy for treatment/management of SARS‑CoV‑2 infection and spread therapy will be developed and implemented in 2021, and we would like to extend our best regards to the frontline health workers across the world in their fight against COVID‑19.
Insulin‐like growth factors (IGF) play important roles in carcinogenesis. The associations of circulating IGF‐1 and insulin‐like growth factor‐binding protein‐3 (IGFBP‐3) with the risks of bladder ...cancer remain unclear. In this large case control study of 2011 bladder cancer cases and 2369 heathy controls, we assessed the associations of circulating IGF‐1 and IGFBP‐3 with bladder cancer risks using a Mendelian randomization approach, which uses genetic variants as instruments to study causal relationship between risk factors and diseases. We first constructed a weighted genetic risk score (GRS) predictive of circulating IGF‐1 and IGFBP‐3 using 413 genome‐wide association study‐identified single nucleotide polymorphisms (SNPs) associated with IGF‐1 and four SNPs with IGFBP‐3, respectively. We found that higher GRS for IGF‐1 was associated with a significantly reduced bladder cancer risk (odds ratio OR = 0.66 per SD increase, 95% confidence interval CI, 0.54–0.82, p < 0.001). We then used a summary statistics‐based MR method, inverse‐variance weighting (IVW), and found a similar risk estimate (OR = 0.67 per SD increase, 95% CI = 0.54–0.83, p < 0.001). When we categorized individuals into high and low IGF‐1 groups using the median GRS value in the controls, the high GRS group had a 21% reduced bladder cancer risk (OR = 0.79, 95% CI = 0.70–0.89) compared to the low GRS group. Genetically predicted circulating IGFBP‐3 was not associated with bladder cancer risk. In conclusion, our data demonstrated for the first time a strong inverse relationship between circulating IGF‐1 level and bladder cancer risk.
Hepatocellular cell carcinoma (HCC) is one of the most commonly diagnosed cancers worldwide and in Taiwan. Chemoprevention of cancer with dietary bioactive compounds could potentially reverse, ...suppress, or prevent cancer progression. Licochalcone A (LicA) is a characteristic chalcone of licorice, which is the root of Glycyrrhiza inflate. It had been reported that LicA has anti-inflammatory, anti-microbial, and anti-tumor properties. However, the effects of LicA on the migration and invasion of human HCC cells have not yet been reported. In the present study, it was found that LicA inhibits the migratory and invasion ability of SK-Hep-1 and HA22T/VGH cells in a dose-dependent manner, as assessed by the cell migration and Matrigel cell invasion assay. Using casein zymography, Western blotting, reverse transcriptase polymerase chain reaction, and an immunofluorescence assay, it was found that LicA induces a dose-dependent inhibition of uPA activity and expression, as well as reduces mRNA levels in SK-Hep-1 and HA22T/VGH cells. LicA was also found to inhibit the expression of phosphor-JNK and phosphor-MKK4 in SK-Hep-1 cells. Furthermore, LicA significantly decreased uPA levels in SP600125-treated or si-MKK4-transfected cells alongside a marked reduction in cell migration and invasion, which supports the notion that an inhibition of MKK4/JNK results in anti-metastatic effects. Moreover, LicA inhibited the expression of nuclear NF-κB, as well as the binding ability of NF-κB to the uPA promoter. These findings further our understanding of the role of LicA in suppressing tumor metastasis and its underlying molecular mechanisms, as well as suggest that LicA may be a promising anti-metastatic agent.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Taiwan has the highest incidence rate of oral cancer in the world. Although oral cancer is mostly an environmentally induced cancer, genetic factors also play an important role in its etiology. ...Genome-wide association studies (GWAS) have identified nine susceptibility regions for oral cancers in populations of European descent. In this study, we performed the first GWAS of oral cancer in Taiwan with 1529 cases and 44,572 controls. We confirmed two previously reported loci on the 6p21.33 (HLA-B) and 6p21.32 (HLA-DQ gene cluster) loci, highlighting the importance of the human leukocyte antigen and, hence, the immunologic mechanisms in oral carcinogenesis. The TERT-CLMPT1L locus on 5p15.33, the 4q23 ADH1B locus, and the LAMC3 locus on 9q34.12 were also consistent in the Taiwanese. We found two new independent loci on 6p21.32, rs401775 in SKIV2L gene and rs9267798 in TNXB gene. We also found two suggestive novel Taiwanese-specific loci near the TPRS1 gene on 8q23.3 and in the TMED3 gene on 15q25.1. This study identified both common and unique oral cancer susceptibility loci in the Taiwanese as compared to populations of European descent and shed significant light on the etiology of oral cancer in Taiwan.
We aimed to investigate the association between genotypes for
and
and the risk of developing colorectal cancer (CRC). We used polymerase chain reaction-restriction fragment length polymorphism ...(PCR-RFLP) to determine the
rs2910164 and
rs11614913 genotypes in 362 CRC patients and 362 controls. We also assessed the interactions between these genotypes and age, gender, smoking, alcohol consumption, and BMI status on CRC risk. Additionally, the serum expression level of mir196a-2 was quantified using quantitative reverse transcription-PCR. Our findings demonstrated that among the controls, the proportions of TT, CT, and CC genotypes of
rs11614913 were 32.3%, 48.1%, and 19.6%, respectively. As for the cases, the proportions were 24.6%, 45.0%, and 30.4%, respectively. Logistic regression analysis revealed that the CC genotype carriers had a 2.04-fold increased risk (95% confidence interval CI = 1.36-3.06,
= 0.0008). Furthermore, carriers of the CT + CC genotypes also exhibited a significant association with CRC risk (odds ratio OR = 1.46, 95% CI = 1.06-2.03,
= 0.0261). Moreover, carriers of the CC genotype had significantly higher serum levels of mir196a-2 compared to those with the TT genotype (
< 0.0001), indicating a genotype-phenotype correlation. No association was found regarding
rs2910164. In conclusion,
rs2910164 genotypes, along with their associated expression, can serve as predictive markers for CRC risk.
We conducted the first genome‐wide association study (GWAS) of prostate cancer (PCa) in Taiwan with 1844 cases and 80,709 controls. Thirteen independent single‐nucleotide polymorphisms (SNPs) reached ...genome‐wide significance (p < 5 × 10−8). Among these, three were distinct from previously identified loci: rs76072851 in CORO2B gene (15q23), odds ratio (OR) = 1.54, 95% confidence interval (CI), 1.36–1.76, p = 5.30 × 10−11; rs7837051, near two long noncoding RNA (lncRNA) genes, PRNCR1 and PCAT2 (8q24.21), OR = 1.41 (95% CI, 1.31–1.51), p = 8.77 × 10−21; and rs56339048, near an lncRNA gene, CASC8 (8q24.21), OR = 1.25 (95% CI, 1.16–1.35), p = 2.14 × 10−8. We refined the lead SNPs for two previously identified SNPs in Taiwanese: rs13255059 (near CASC8), p = 9.02 × 10−43, and rs1456315 (inside PRNCR1), p = 4.33 × 10−42. We confirmed 35 out of 49 GWAS‐identified East Asian PCa susceptibility SNPs. In addition, we identified two SNPs more specific to Taiwanese than East Asians: rs34295433 in LAMC1 (1q25.3) and rs6853490 in PDLIM5 (4q22.3). A weighted genetic risk score (GRS) was developed using the 40 validated SNPs and the area under the receiver‐operating characteristic curve for the GRS to predict PCa was 0.67 (95% CI, 0.63–0.71). These identified SNPs provide valuable insights into the molecular mechanisms of prostate carcinogenesis in Taiwan and underscore the significant role of genetic susceptibility in regional differences in PCa incidence.
Matrix metalloproteinase-2 (MMP-2) plays a critical role in the regulation of the extracellular matrix; however, its genotypes have seldom been examined in gastric cancer (GC). This study aimed to ...investigate the contribution of MMP-2 promoter -1306 (rs243865) and -735 (rs2285053) genotypes to GC risk in a cohort of Taiwanese individuals.
This study included 121 GC cases and 363 age- and sex-matched controls. The genotypes of MMP-2 were determined by typical polymerase chain reaction-restriction fragment length polymorphism.
The genotypic and allelic frequency analysis showed that MMP-2 rs243865 variant genotypes decreased the risk of GC. Stratification analysis showed that MMP-2 rs243865 genotypes associate with smoking, alcohol drinking, and Helicobacter pylori infection status to confer personal susceptibility to GC. There is no such association for MMP-2 rs2285053 genotype with GC risk.
The MMP-2 rs243865 genotypes may serve as a novel predictive marker for GC personal susceptibility among Taiwanese.
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