Capsaicin reverses cisplatin resistance in tongue squamous cell carcinoma by inhibiting the Warburg effect and facilitating mitochondrial-dependent apoptosis via the AMPK/AKT/mTOR axis.

Cisplatin is commonly used for the chemotherapy of tongue squamous cell carcinoma (TSCC); however, adverse side effects and drug resistance impact its therapeutic efficacy. Capsaicin is an active ingredient in chili peppers that exerts antitumor effects, whether it exerts antitumor effects on cisplatin-resistant cells remains unknown. Therefore, in this study, we investigated the effect of capsaicin on cisplatin resistance in TSCC cells and explored the underlying mechanisms. A cisplatin-resistant TSCC cell line was established by treated with increasing cisplatin concentrations. Combined treatment with cisplatin and capsaicin decreased the glucose consumption and lactate dehydrogenase activity and increased the adenosine triphosphate production both in vitro and in vivo, suggesting the inhibition of the Warburg effect. Moreover, this combined treatment induced cell apoptosis and significantly upregulated the levels of proapoptotic proteins, such as Bax, cleaved caspase-3, -7, and -9, and apoptosis-inducing factor. In contrast, levels of the antiapoptotic protein, Bcl-2, were downregulated. Additionally, LKB1 and AMPK activities were stimulated, whereas those of AKT and mTOR were suppressed. Notably, AMPK knockdown abolished the inhibitory effects of capsaicin and cisplatin on the AKT/mTOR signaling pathway and Warburg effect. Overall, combined treatment with capsaicin and cisplatin reversed cisplatin resistance by inhibiting the Warburg effect and facilitating mitochondrial-dependent apoptosis via the AMPK/AKT/mTOR axis. Our findings suggest combination therapy with capsaicin and cisplatin as a potentially novel strategy and highlight capsaicin as a promising adjuvant drug for TSCC treatment.

[Research progress on antitumor effect and molecular mechanism of capsaicin].

Capsaicin is a lipid-soluble vanillin alkaloid extracted from Capsicum plants in the Solanaceae family, which is the main active ingredient in capsicum, with multiple functions such as anti-inflammation, analgesia, cardiovascular expansion, and gastric mucosa protection. Recently, capsaicin has been confirmed as a potential antitumor compound. It can induce cell cycle arrest, inhibit cancer cell proliferation, metastasis, invasion, and angiogenesis, and promote apoptosis or autophagy in malignancy cell models and animal models of lung cancer, breast cancer, gastric cancer, and liver cancer. Meanwhile, capsaicin shows a synergistic antitumor effect when combined with other antitumor drugs such as sorafenib. Based on the recent literature on the antitumor effect of capsaicin, the present study analyzed the molecular mechanism of capsaicin in resisting tumors by inducing apoptosis and reviewed the effects of capsaicin in inducing tumor cell cycle arrest, inhibiting tumor cell proliferation, metastasis, and angiogenesis, and combating tumors with other drugs, thereby providing a theoretical basis for further research of capsaicin and its rational development and utilization.

Molecular subtyping and antimicrobial susceptibilities of Campylobacter coli isolates from diarrheal patients and food-producing animals in China.

The aim of this study was to determine the molecular subtyping and antimicrobial susceptibility characteristics of Campylobacter coli isolates from different sources in China. One hundred thirteen C. coli isolates were subtyped by pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST), and porA and flaA short variable region (SVR) nucleotide sequences. Cluster analysis was performed based on the PFGE and sequence types (ST). Eighty-four PFGE patterns (SmaI) were observed in 113 isolates. Fifty-four STs (28 novel) and three clonal complexes (CC), 86% of which were clustered to CC828, were observed, as well as 52 porA and 37 flaA-SVR sequence alleles. MLST, porA, and flaA-SVR analysis demonstrated that many isolates from diarrheal patients shared identical genotypes with chicken isolates. Minimum inhibitory concentration values of 10 antibiotics were analyzed for 109 isolates isolated in 2011 using the E-test method. The most frequently observed resistance agents were nalidixic acid (100%) and ciprofloxacin (100%), followed by levofloxacin (99%), tetracycline (94%), metronidazole (93%), erythromycin (61%), streptomycin (72%), gentamicin (59%), ampicillin (50%), and chloramphenicol (29%). Multidrug resistance was detected in 108 of 109 C. coli isolates (99%).

The activation of adenosine monophosphate-activated protein kinase inhibits the migration of tongue squamous cell carcinoma cells by targeting Claudin-1 via epithelial-mesenchymal transition.

BACKGROUND: The role of Claudin-1 in tongue squamous cell carcinoma (TSCC) metastasis needs further clarification, particularly its impact on cell migration. Herein, our study aims to investigate the role of Claudin-1 in TSCC cell migration and its underlying mechanisms. METHODS: 36 TSCC tissue samples underwent immunohistochemical staining for Claudin-1. Western blotting and immunofluorescence analyses were conducted to evaluate Claudin-1 expression and distribution in TSCC cells. Claudin-1 knockdown cell lines were established using short hairpin RNA transfection. Migration effects were assessed through wound healing assays. Furthermore, the expression of EMT-associated molecules was measured via western blotting. RESULTS: Claudin-1 expression decreased as TSCC malignancy increased. Adenosine monophosphate-activated protein kinase (AMPK) activation led to increased Claudin-1 expression and membrane translocation, inhibiting TSCC cell migration and epithelial-mesenchymal transition (EMT). Conversely, Claudin-1 knockdown reversed these inhibitory effects on migration and EMT caused by AMPK activation. CONCLUSIONS: Our results indicated that AMPK activation suppresses TSCC cell migration by targeting Claudin-1 and EMT pathways.

Capsaicin exerts synergistic pro-apoptotic effects with cisplatin in TSCC through the calpain pathway via TRPV1.

Capsaicin (CAP) exerts significant anti-tumor effects on a variety of tumors, with low intrinsic toxicity. Cisplatin (DDP) is currently the first-line drug for the treatment of oral cancer; however, its clinical efficacy is impeded by chemoresistance and negligible side effects. Whether the combined use of CAP and DDP has a synergistic antitumor effect on tongue squamous cell carcinoma (TSCC) cells and its underlying mechanisms remains unclear. The present study revealed that CAP reduced the activity of TSCC cells in a dose- and time-dependent manner. We also observed changes in the mitochondrial functional structure of TSCC cells, along with the induction of mitochondrial apoptosis. Moreover, when CAP was combined with DDP, a synergistic cytotoxic effect on TSCC cells was observed, which had a significant impact on inducing apoptosis, inhibiting proliferation, and disrupting the mitochondrial membrane potential in TSCC cells compared to the single-drug treatment and control groups. These effects are associated with TRPV1, a high-affinity CAP receptor. The combined use of CAP and DDP can activate the TRPV1 receptor, resulting in intracellular Ca2+ overload and activation of the calpain pathway, ultimately leading to mitochondrial apoptosis. This potential mechanism was validated in TSCC xenograft models. In conclusion, our findings clearly demonstrate that CAP exerts synergistic pro-apoptotic effects with DDP in TSCC through the calpain pathway mediated by TRPV1. Thus, CAP can be considered an effective adjuvant drug for DDP in the treatment of TSCC.

Support networks for Chinese older immigrants accessing English health and social care services: the concept of Bridge People.

As Chinese immigrants in the United Kingdom age, they experience an increasing need to access health and care services. It has, however, been reported that older Chinese immigrants have difficulties in accessing these services. This study explored the experiences of this population in using health and care services and the strategies that they adopted to address their difficulties. A grounded theory method with a two-staged research design was used. Stage 1 explored the participants' experiences of ageing and use of health and social care services through focus group interviews. Stage 2 investigated the strategies individuals used to support access to and use of services through individual interviews. Forty-four older Chinese people and 15 supporters participated in interviews during August 2011 and May 2013. These older Chinese immigrants were challenged in knowing about and in accessing services. Their difficulties were attributed to language barriers, lack of information and instrumental support, and emotional and cultural issues regarding use of health and care services. Their supporters facilitated access to services and acted as a bridge between the service and the user; therefore, they were given the title 'Bridge People'. Bridge People have different backgrounds: family and friends, public sector workers and staff from community-based Chinese organisations. The defining attributes of these supporters were: bilinguality, bicultural, multifunctionality and accessibility. There is no charge for this support; and the relationship between the Bridge Person and recipient involves trust and influence over decisions regarding use of health and care services. Bridge People should be recognised and identified by health, social care and housing services to promote engagement and use of services by older immigrant Chinese people.

Genome Sequences of the Guillain-Barre Syndrome Outbreak-Associated Campylobacter jejuni Strains ICDCCJ07002 and ICDCCJ07004.

The first world-known and largest outbreak of 36 cases of Guillain-Barré syndrome caused by a preceding Campylobacter jejuni infection was reported previously in China. During the outbreak, Campylobacter jejuni strain ICDCCJ07002 was isolated from a patient with persistent diarrhea for 21 days, and C. jejuni strain ICDCCJ07004 was from a healthy carrier without any clinical symptoms at the same time. Here, we report the draft genome sequence of strain ICDCCJ07002 (1,698,407 bp, with a G+C content of 30.45%) and the genome resequencing result of strain ICDCCJ07004 (1,701,584 bp, with a G+C content of 30.51%), and we compared these with the completed genome of C. jejuni strain ICDCCJ07001.