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Coronavirus disease 2019 (COVID-19) has been spreading worldwide with a mind-boggling speed According to a statement from World Health Organization (WHO), COVID-19 has infected more than six billions people and caused more than one and half million passing in the world Based on previous experience with SARS, the Taiwanese government had decided to block viral transmission during its early stages This review sums up the clinical characteristics, Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) viral infection process, diagnostic methods, preventive strategy, and the executive proportions of COVID-19, as well as the name-based mask distribution system (NBMDS) in Taiwan We also give a review of the conceivable sub-atomic pharmacologic systems against SARS-CoV-2 specialists and the blend of remdesivir (GS-5734), chloroquine (CQ), and hydroxychloroquine (HCQ) Lastly, we summarized the therapeutic agents against COVID-19 as mentioned by COVID-19 treatment guidelines In this review, development of novel anti-SARS-CoV-2 viral agents, vaccines for COVID-19 therapy or an effective combination therapy can be expected based on all the information accumulated Last but not least, we might want to stretch out our best respects to all medical providers in their worldwide battle against COVID-19

Novel quinazolinone compounds have been studied in the field of drug discovery for a long time. Among their broad range of pharmacological effects, certain compounds effectively inhibit cancer cell proliferation. MJ-33 is a quinazolinone derivative with proposed anticancer activities that was synthesized in our laboratory. The present study aimed to evaluate the anticancer activity of MJ-33 in fluorouracil (5FU)-resistant colorectal cancer cells (HT-29/5FUR) and to investigate the underlying molecular mechanisms. The cell viability assay results indicated that HT-29/5FUR cell viability was inhibited by MJ-33 treatment in a concentration-dependent manner compared with the control group. The cellular morphological alterations observed following MJ-33 treatment indicated the occurrence of apoptosis and autophagy, as well as inhibition of cell proliferation in a time-dependent manner compared with the control group. The acridine orange, LysoTracker Red and LC3-green fluorescent protein staining results indicated that MJ-33 treatment significantly induced autophagy compared with the control group. The DAPI/TUNEL dual staining results demonstrated increased nuclear fragmentation and condensation following MJ-33 treatment compared with the control group. The Annexin V apoptosis assay and image cytometry analysis results demonstrated a significant increase in apoptotic cells following MJ-33 treatment compared with the control group. The western blotting results demonstrated markedly decreased Bcl-2, phosphorylated (p)-BAD, pro-caspase-9 and pro-caspase-3 expression levels, and notably increased cytochrome c and apoptotic peptidase activating factor 1 expression levels following MJ-33 treatment compared with the control group. Moreover, the expression levels of autophagy-related proteins, including autophagy related (ATG)-5, ATG-7, ATG-12, ATG-16, p62 and LC3-II, were increased following MJ-33 treatment compared with the control group. Furthermore, MJ-33-treated HT-29/5FUR cells displayed decreased expression levels of p-AKT and p-mTOR compared with control cells. The results suggested that MJ-33-induced apoptosis was mediated by AKT signaling, and subsequently modulated via the mitochondria-dependent signaling pathway. Therefore, the results suggested that suppression of AKT/mTOR activity triggered autophagy in the HT-29/5FUR cell line. In summary, the results indicated that MJ-33 inhibited HT-29/5FUR cell viability, and induced apoptosis and autophagy via the AKT/mTOR signaling pathway. The present study may provide novel insight into the anticancer effects and mechanisms underlying MJ-33 in 5FU-resistant colorectal cancer cells.

Melanoma is a malignant tumor with aggressive behavior. Vemurafenib, a BRAF inhibitor, is clinically used in melanoma, but resistance to melanoma cytotoxic therapies is associated with BRAF mutations. Curcumin can effectively inhibit numerous types of cancers. However, there are no reports regarding the correlation between curcumin and vemurafenib-resistant melanoma cells. In this study, vemurafenib-resistant A375.S2 (A375.S2/VR) cells were established, and the functional mechanism of the epidermal growth factor receptor (EGFR), serine-threonine kinase (AKT), and the extracellular signal-regulated kinase (ERK) signaling induced by curcumin was investigated in A375.S2/VR cells in vitro. Our results indicated that A375.S2/VR cells had a higher IC

Dracorhodin can be isolated from the exudates of the fruit of Daemonorops draco. Previous studies suggested that dracorhodin perchlorate can promote fibroblast proliferation and enhance angiogenesis during wound healing. In the present study, the potential bioactivity of dracorhodin perchlorate in human HaCaT keratinocytes, were investigated in vitro, with specific focus on HaCaT wound healing. The results of in vitro scratch assay demonstrated the progressive closure of the wound after treatment with dracorhodin perchlorate in a time-dependent manner. An MTT assay and propidium iodide exclusion detected using flow cytometry were used to detect cell viability of HaCaT cells. Potential signaling pathways underlying the effects mediated by dracorhodin perchlorate in HaCaT cells were clarified by western blot analysis and kinase activity assays. Dracorhodin perchlorate significantly increased the protein expression levels of β-catenin and activation of AKT, ERK and p38 in HaCaT cells. In addition, dracorhodin perchlorate did not induce HaCaT cell proliferation but promoted cell migration. Other mechanisms may yet be involved in the dracorhodin perchlorate-induced wound healing process of human keratinocytes. In summary, dracorhodin perchlorate may serve to be a potential molecularly-targeted phytochemical that can improve skin wound healing.

Coronavirus disease 2019 (COVID-19) has been spreading worldwide with a mind-boggling speed. According to a statement from World Health Organization (WHO), COVID-19 has infected more than six billions people and caused more than one and half million passing in the world. Based on previous experience with SARS, the Taiwanese government had decided to block viral transmission during its early stages. This review sums up the clinical characteristics, Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) viral infection process, diagnostic methods, preventive strategy, and the executive proportions of COVID-19, as well as the name-based mask distribution system (NBMDS) in Taiwan. We also give a review of the conceivable sub-atomic pharmacologic systems against SARS-CoV-2 specialists and the blend of remdesivir (GS-5734), chloroquine (CQ), and hydroxychloroquine (HCQ). Lastly, we summarized the therapeutic agents against COVID-19 as mentioned by COVID-19 treatment guidelines. In this review, development of novel anti-SARS-CoV-2 viral agents, vaccines for COVID-19 therapy or an effective combination therapy can be expected based on all the information accumulated. Last but not least, we might want to stretch out our best respects to all medical providers in their worldwide battle against COVID-19.

The coronavirus disease 2019 (COVID-19) outbreak, which has caused millions of confirmed infections and thousands of deaths, has been the most devastating worldwide crises recently. The main clinical symptoms of confirmed COVID-19 cases include fever, dry cough, general fatigue, respiratory symptoms, diarrhoea and sore throat, similar to those of acute respiratory distress syndrome. SARS-CoV-2, the causative agent of COVID-19, belongs to a novel coronavirus strain against which no drug or vaccine currently exists. Therefore, research units around the world have been actively developing efficient diagnostic tools and new drugs. This review summarises the clinical manifestations of COVID-19, analyses the viral genome sequence and life cycle, identifies methods for preventing viral transmission, discusses possible molecular pharmacologic mechanisms and approaches in the development of anti-SARS-CoV-2 virus therapeutic agents and introduces management measures against COVID-19 in Taiwan, especially policies for a name-based mask distribution system. Finally, we summarise traditional Chinese medicines (TCM) for COVID-19. Based on all the information accumulated in this review, development of novel anti-viral agents, vaccines for SARS-CoV-2 therapy or an effective combination therapy can be expected. Finally, we would like to extend our best regards to the frontline health workers in their global fight against COVID-19.

Diabetes mellitus (DM) is a chronic disease. The KK Cg-Ay/J (KK-Ay) mouse is an animal model to study type 2 diabetes mellitus (T2D) disease. The present study assessed the expression of hematopoietically expressed homeobox (HHEX) protein in liver tissues of different age groups of mice (6, 16 and 42 weeks) by immunohistochemistry (IHC). The results demonstrated a significant decrease in the percentage of HHEX-positive cells in KK-Ay mice as compared with that in KK-α/α control mice. Furthermore, in Taiwan's Han Chinese population, genotypic and allelic frequency distributions of the rs61862780 single-nucleotide polymorphism (SNP) in the HHEX gene were investigated. The results demonstrated that in the rs61862780 SNP of the 3'-untranslated region (UTR) of HHEX, the frequency of the CC genotype was higher in patients (6.0%) than in controls (2.7%), while the TT genotype frequency was about equal. In the same SNP, the frequency of the C allele was higher in patients (21.0%) than in controls (17.3%), while the T allele frequency was about equal. These results may pave the road for exploring the KK-Ay mouse model and the HHEX SNP rs61862780, which was correlated with the susceptibility to T2D in a Chinese population. Based on these findings, an association of HHEX gene expression with pathological features of T2D was indicated.

Osteosarcoma is the most common primary malignancy of the bone and is characterized by local invasion and distant metastasis. Over the past 20 years, long-term outcomes have reached a plateau even with aggressive therapy. Overexpression of insulin-like growth factor 1 receptor (IGF‑1R) is associated with tumor proliferation, invasion and migration in osteosarcoma. In the present study, our group developed a novel quinazoline derivative, 6-fluoro‑2-(3-fluorophenyl)-4-(cyanoanilino)quinazoline (HMJ‑30), in order to disrupt IGF‑1R signaling and tumor invasiveness in osteosarcoma U‑2 OS cells. Molecular modeling, immune-precipitation, western blotting and phosphorylated protein kinase sandwich ELISA assays were used to confirm this hypothesis. The results demonstrated that HMJ‑30 selectively targeted the ATP-binding site of IGF‑1R and inhibited its downstream phosphoinositide 3-kinase/protein kinase B, Ras/mitogen-activated protein kinase, and IκK/nuclear factor-κB signaling pathways in U‑2 OS cells. HMJ‑30 inhibited U‑2 OS cell invasion and migration and downregulated protein levels and activities of matrix metalloproteinase (MMP)‑2 and MMP-9. An increase in protein levels of tissue inhibitor of metalloproteinase (TIMP)‑1 and TIMP‑2 was also observed. Furthermore, HMJ‑30 caused U‑2 OS cells to aggregate and form tight clusters, and these cells were flattened, less elongated and displayed cobblestone-like shapes. There was an increase in epithelial markers and a decrease in mesenchymal markers, indicating that the cells underwent the reverse epithelial-mesenchymal transition (EMT) process. Overall, these results demonstrated the potential molecular mechanisms underlying the effects of HMJ‑30 on invasiveness and EMT in U‑2 OS cells, suggesting that this compound deserves further investigation as a potential anti-osteosarcoma drug.

Pterostilbene is a natural polyphenolic compound that is primarily found in fruits, such as blueberries and has a similar structure to resveratrol. Pterostilbene exhibits antioxidant, anti-inflammatory and antitumor activity but the effects of pterostilbene on drug-resistant oral cancer cells and its underlying mechanisms of action have not yet been explored. Therefore, the present study was performed to clarify the anticancer effects of pterostilbene on cisplatin-resistant human oral cancer CAR cells. The results demonstrated that CAR cells exhibited marked shrinkage, cell membrane breakage and autophagic vacuole formation following treatment with pterostilbene. Pterostilbene also effectively inhibited cell viability and suppressed cell confluence in a time- and concentration-dependent manner. Probing with acridine orange, monodansylcadaverine and LysoTracker Red demonstrated that the number of acidic vesicular organelles was increased, indicating increased autophagy. Furthermore, Heochst 33342 staining determined that DNA condensation, a characteristic of apoptosis, was enhanced following treatment with pterostilbene. Furthermore, pterostilbene upregulated mRNA levels of LC3-II and Atg12, as well as the expression of Atgs/Beclin-1/LC3-associated signaling, suggesting that it enhances autophagy. The autophagy inhibitors 3-methyladenine and chloroquine were used to confirm that pterostilbene induces autophagy. It was also determined that pterostilbene triggered caspase-dependent apoptosis by directly testing DNA breakage and using the pan-caspase inhibitor carbobenzoxyvalyl-alanyl-aspartyl fluoromethyl ketone. The results demonstrated that pterostilbene mediates the apoptosis of CAR cells via the intrinsic apoptotic cascade. In addition, pterostilbene inhibited MDR1 expression and the phosphorylation of AKT on the Ser473 site in CAR cells. Therefore, pterostilbene may elicit an oral anticancer response in drug-resistant cells and may be used as a chemotherapeutic adjuvant to treat patients with oral cancer.

Oral squamous cell carcinoma (OSCC) is a type of cancer with high morbidity and mortality rates worldwide; it also demonstrates chemotherapeutic resistance. Triterpenoid ursolic acid has been shown to exhibit various biological activities and anticancer effects in several preclinical studies. In our previous study, human cisplatin‑resistant oral cancer CAR cells were established, and the present study aimed to further examine the effects of ursolic acid on CAR cells. The results revealed that ursolic acid inhibited CAR cell viability, as determined using a 3‑(4,5‑dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide assay. Ursolic acid‑induced cell death was mediated through a caspase‑dependent pathway, determined with the pan‑caspase inhibitor, z‑VAD‑fmk. Ursolic acid also increased the activities of caspase‑3 and caspase‑9 in CAR cells, determined by a colorimetric assay. Specifically, the production of reactive oxygen species and loss of mitochondrial membrane potential, detected by flow cytometry, were observed in the ursolic acid‑treated CAR cells. The apoptosis‑associated signaling showed that ursolic acid decreased the phosphorylation of AKT (Ser473) and B‑cell lymphoma 2 (Bcl‑2)‑associated agonist of cell death (BAD; Ser136), and the protein levels of Bcl‑2 and Bcl‑extra large (Bcl‑xL), and increased the expression of BAD and Bcl‑2‑associated X (Bax) protein in CAR cells. In summary, the results supported the potential application of ursolic acid against drug‑resistant oral carcinoma and to improve oral anticancer efficacy in the near future.

Background/aim Gadoxetate disodium (Primovist or Eovist) is extensively used as a hepatospecific contrast agent during magnetic resonance imaging (MRI) examinations. However, there is no information determining whether gadoxetate disodium has a cytotoxic impact and/or affects relative gene expression on liver cells. In the current study, we investigated the effects of gadoxetate disodium on cytotoxicity and the levels of gene expression in human normal Chang Liver cells. Materials and methods The cytotoxic effect was detected via methyl thiazolyl tetrazolium (MTT) assay and 4',6-diamidino-2-phenylindole (DAPI) staining. mRNA expression was monitored by cDNA microarray and quantitative PCR (qPCR) analysis. The protein levels were determined by western blotting. Results Gadoxetate disodium at 5 and 10 mM failed to induce any cell cytotoxicity and morphological changes in Chang Liver cells. Our data demonstrated that gadoxetate disodium significantly enhanced the expression of 29 genes and suppressed that of 27. The SLCO1C1 (solute carrier organic anion transporter family member 1C1) mRNA expression was also increased by 2.62-fold (p-value=0.0006) in gadoxetate disodium-treated cells. Furthermore, we also checked and found that gadoxetate disodium up-regulated organic anion transporter polypeptide 1B1 (OATP1B1) protein level and increased OATP uptake transporter gene SLCO1C1 mRNA expression. Conclusion Our results provide evidence regarding that gadoxetate disodium might be no cytotoxic effects on liver cells.

Oral cancer is a serious and fatal disease. Cisplatin is the first line of chemotherapeutic agent for oral cancer therapy. However, the development of drug resistance and severe side effects cause tremendous problems clinically. In this study, we investigated the pharmacologic mechanisms of YC-1 on cisplatin-resistant human oral cancer cell line, CAR. Our results indicated that YC-1 induced a concentration-dependent and time-dependent decrease in viability of CAR cells analyzed by MTT assay. Real-time image analysis of CAR cells by IncuCyte™ Kinetic Live Cell Imaging System demonstrated that YC-1 inhibited cell proliferation and reduced cell confluence in a time-dependent manner. Results from flow cytometric analysis revealed that YC-1 promoted G0/G1 phase arrest and provoked apoptosis in CAR cells. The effects of cell cycle arrest by YC-1 were further supported by up-regulation of p21 and down-regulation of cyclin A, D, E and CDK2 protein levels. TUNEL staining showed that YC-1 caused DNA fragmentation, a late stage feature of apoptosis. In addition, YC-1 increased the activities of caspase-9 and caspase-3, disrupted the mitochondrial membrane potential (AYm) and stimulated ROS production in CAR cells. The protein levels of cytochrome c, Bax and Bak were elevated while Bcl-2 protein expression was attenuated in YC-1-treated CAR cells. In summary, YC-1 suppressed the viability of cisplatin-resistant CAR cells through inhibiting cell proliferation, arresting cell cycle at G0/G1 phase and triggering mitochondria-mediated apoptosis. Our results provide evidences to support the potentially therapeutic application of YC-1 on fighting against drug resistant oral cancer in the future.

Diabetes mellitus (DM) is a chronic disease. The KK Cg-Ay/J (KK-Ay) mouse is an animal model to study type 2 diabetes mellitus (T2D) disease. The present study assessed the expression of hematopoietically expressed homeobox (HHEX) protein in liver tissues of different age groups of mice (6, 16 and 42 weeks) by immunohistochemistry (IHC). The results demonstrated a significant decrease in the percentage of HHEX-positive cells in KK-Ay mice as compared with that in KK-α/α control mice. Furthermore, in Taiwan's Han Chinese population, genotypic and allelic frequency distributions of the rs61862780 single-nucleotide polymorphism (SNP) in the HHEX gene were investigated. The results demonstrated that in the rs61862780 SNP of the 3′-untranslated region (UTR) of HHEX, the frequency of the CC genotype was higher in patients (6.0%) than in controls (2.7%), while the TT genotype frequency was about equal. In the same SNP, the frequency of the C allele was higher in patients (21.0%) than in controls (17.3%), while the T allele frequency was about equal. These results may pave the road for exploring the KK-Ay mouse model and the HHEX SNP rs61862780, which was correlated with the susceptibility to T2D in a Chinese population. Based on these findings, an association of HHEX gene expression with pathological features of T2D was indicated.