The palliative role of lasers in the treatment of melanoma.

Melanoma, accounting for a significant proportion of skin cancer-related deaths, has variable survival outcomes based on the stage at diagnosis and treatment efficacy. Traditional treatments, while effective, pose risks of scarring and systemic side effects. Laser therapy offers an emerging non-surgical alternative, with CO2 lasers particularly showing promise in palliative care.A comprehensive search was conducted using PubMed, focusing on laser therapy for melanoma treatment. The search included studies on both stand-alone and adjunct laser therapies, with inclusion criteria requiring peer-reviewed articles detailing treatment outcomes for primary, recurrent, or metastatic melanoma.The literature shows that laser therapy for melanoma falls into four major types when categorized by laser medium: solid-state, diode, pulse-dye, and gas (CO2). Data on solid-state lasers for melanoma are limited and their use remains controversial. However, one study with high-energy pulsed neodymium lasers reported a 5-year survival of 82.9% with minimal adverse effects for primary melanoma. CO2 laser therapy has been effective for palliative treatment, with one study showing 54.8% of patients with recurrent melanoma surviving 5.4 years post-ablation. For metastatic melanoma, numerous studies have shown that CO2 laser therapy can provide symptomatic relief and disease control. Combination therapies using lasers and immune-based therapies have demonstrated enhanced outcomes and immune activation, highlighting the potential of laser therapies in melanoma management.While traditional treatments remain the standard for primary melanoma, laser therapies, particularly CO2 laser ablation, show substantial promise in palliative care for metastatic melanoma. Careful patient selection and assessment are crucial for achieving positive outcomes.

Modified Application of the Abdominal Re-Approximation Anchor Device in the Closure of Septic Open Abdomen in a Patient With Class III Obesity.

The Abdominal Re-Approximation Anchor (ABRA®) is a pivotal dynamic wound closure system utilized for achieving primary fascial closure in patients undergoing open abdomen surgeries. However, its efficacy can be hindered in patients with class III obesity due to anatomical complexities and compromised tissue characteristics. Here, we present the unique case of a 25-year-old woman with class III obesity (body mass index (BMI) ≥ 40 kg/m2) who required primary abdominal closure following complications of an ileostomy repair. Traditional placement of the ABRA device was not feasible due to thick subcutaneous tissue layers. Consequently, a modified application of ABRA was decided based on clinical judgment, whereby the ABRA button anchors were strategically placed internally under the subcutaneous tissue instead of externally on the skin surface. The patient completed six intraoperative tightenings of the ABRA device via this novel technique and was treated with washouts over the course of two months until complete resolution was achieved. The presented case demonstrates a successful modification of the ABRA wound closure device to suit an open abdomen patient with class III obesity.

The role of vitamins and nutrients in rosacea.

Rosacea is a common inflammatory skin condition displaying symptoms like flushing, erythema, papules, and pustules. Oral antibiotics, despite long-term adverse effects, are often used due to topical treatment limitations, underscoring the need for cost-effective choices like dietary modifications. Our review investigates the role of vitamins and minerals in rosacea, and provides evidence-based recommendations for supplementation and topical treatment of these nutrients for rosacea. An online search was performed on PubMed, Web of Science, Science Direct, Google Scholar, and ClinicalTrials.gov from 1998 to 2023. Included studies were summarized and assessed for quality and relevance in rosacea management. Varied outcomes emerged concerning the impact of essential vitamins and minerals on rosacea treatment. Vitamin A derivatives, specifically oral isotretinoin, demonstrated significant efficacy, with a 90% reduction in lesions, complete remission in 24% of patients, and marked improvement in 57% of patients. Vitamin B3 derivatives, such as topical 1-methylnicotinamide 0.25% and NADH 1%, improved symptoms in 76.4% (26/34) and 80% of patients, respectively. Outcomes for vitamin D, vitamin C, and zinc supplementation varied across studies. However, zinc sulfate solution 5% significantly reduced acne rosacea severity for patients with 40% and 60% exhibiting a moderate or good response, respectively. Omega-3 fatty acids showed significant improvement in alleviating xerophthalmia in 64% of patients with ocular rosacea. Vitamins and minerals hold potential in managing rosacea symptoms, offering a safe and cost-effective alternative or adjunctive treatment option. Currently, there are no established recommendations regarding their supplementation for rosacea. Studies assessing serum levels of vitamins and minerals in relation to rosacea are warranted, as this avenue holds potential for future advancements in the field.

Pancreatic cancer cells upregulate LPAR4 in response to isolation stress to promote an ECM-enriched niche and support tumour initiation.

Defining drivers of tumour initiation can provide opportunities to control cancer progression. Here we report that lysophosphatidic acid receptor 4 (LPAR4) becomes transiently upregulated on pancreatic cancer cells exposed to environmental stress or chemotherapy where it promotes stress tolerance, drug resistance, self-renewal and tumour initiation. Pancreatic cancer cells gain LPAR4 expression in response to stress by downregulating a tumour suppressor, miR-139-5p. Even in the absence of exogenous lysophosphatidic acid, LPAR4-expressing tumour cells display an enrichment of extracellular matrix genes that are established drivers of cancer stemness. Mechanistically, upregulation of fibronectin via an LPAR4/AKT/CREB axis is indispensable for LPAR4-induced tumour initiation and stress tolerance. Moreover, ligation of this fibronectin-containing matrix via integrins α5ß1 or αVß3 can transfer stress tolerance to LPAR4-negative cells. Therefore, stress- or drug-induced LPAR4 enhances cell-autonomous production of a fibronectin-rich extracellular matrix, allowing cells to survive 'isolation stress' and compensate for the absence of stromal-derived factors by creating their own tumour-initiating niche.

Introducing surface-to-surface matching technique to evaluate mandibular symmetry: A retrospective study.

Objectives: This study introduced a three-dimensional (3D) surface-to-surface matching technique to evaluate the mandibular symmetry of teenagers and adults with unilateral second molar scissor bite. Methods: The targets came from 73 cone-beam computed tomography (CBCT) images with unilateral second molar scissor bite, including teenagers (n = 30) and adults (n = 43). 73 images without scissor bite and matched in sex and age were selected as controls. The scans were developed into 3D mandible models and seven mandibular functional unit models, including condylar process (Co), coronoid process (Cr), mandibular ramus (Ra), mandibular angle (Ma), alveolar process (Ap), mandibular body (Mb) and chin process (Ch). The surface-to-surface matching technique was introduced. 3D deviation analysis and matching percentages calculation were performed and compared to evaluate the symmetry of the mandible. Results: Comparisons were made between the study samples and control samples. For teenagers, the matching percentages of the entire mandible (55.31 ± 7.24%), Mb (69.04 ± 9.22%) and Co (65.19 ± 10.67%) in the study group were lower than that of the entire mandible (60.87 ± 6.38%) (P <0.01), Mb (75.0 ± 8.71%) (P <0.05) and Co (70.25 ± 8.20%) (P <0.05) in the control group. While Ap, Ra, Ch, Cr and Ma showed no statistically significant differences (P >0.05). For adults, the matching percentages of the entire mandible (48.88 ± 9.77%), Ap (65.83 ± 11.21%), Mb (64.43 ± 12.03%), Ch (79.17 ± 10.29%), Ra (64.11 ± 9.84%) and Co (61.08 ± 11.64%) in the study group were lower than the entire mandible (59.28 ± 5.49%) (P <0.01), Ap (73.65 ± 9.10%) (P <0.01), Mb (71.66 ± 8.40%) (P <0.01), Ch (83.86 ± 5.59%) (P <0.05), Ra (68.54 ± 7.87%) (P <0.05) and Co (66.20 ± 10.62%) (P <0.05) of the control group. Only Cr and Ma showed no statistically significant differences (P >0.05). Conclusion: Mandibular asymmetry was observed in both teenagers and adults with unilateral second molar scissor bite. Moreover, compared with teenagers, more mandibular units of adult patients were affected. Clinical significance: Based on the surface-to-surface matching technique, the symmetric and morphological information of the mandible can be converted into visual color maps and quantitative descriptions. This method can bring convenience to the study of the growth of mandible, orthodontic treatment and orthognathic surgery design.

Bicyclol ameliorates advanced liver diseases in murine models via inhibiting the IL-6/STAT3 signaling pathway.

Bicyclol, a synthetic hepatoprotective and anti-inflammatory agent approved in China, was widely used to treat various hepatitis accompanied by elevated serum aminotransferases. However, the pharmacological effects and mechanisms of bicyclol on advanced liver diseases, such as fibrosis/cirrhosis and hepatocellular carcinoma (HCC), remain to be explored. Here, we revealed that bicyclol prevents from formatting severe fibrosis, slows the progression of moderate liver fibrosis, accelerates the regression of moderate liver fibrosis, decreases the malignancy of HCC in rat models induced by diethylnitrosamine (DEN), and also blocks steatohepatitis to HCC in mice induced by western diet plus carbon tetrachloride and DEN. The detailed pharmacological mechanism showed that bicyclol alleviates chronic progressive liver diseases by inhibiting the levels of IL-6 and subsequent phosphorylated STAT3. Conclusion: Bicyclol plays significant protective roles in multiply stages of fibrosis/cirrhosis-HCC and nonalcoholic fatty liver disease-related HCC via inhibiting IL-6/STAT3 signaling pathway. Therefore, bicyclol might be a promising therapeutic strategy for treating advanced liver diseases.

Design, Synthesis, and Biological Evaluation of 2-((4-Bisarylmethyl-piperazin-1-yl)methyl)benzonitrile Derivatives as HCV Entry Inhibitors.

Viral entry inhibitors are absent in hepatitis C virus (HCV) treatment regimens although a dozen direct-acting antiviral (DAA) drugs are available now. Based on a previously identified HCV entry inhibitor L0909, chemical space exploration and structure-activity relationship (SAR) studies led to the discovery of a new derived scaffold 2-((4-bisarylmethyl-piperazin-1-yl)methyl)benzonitrile. Several new scaffold derivatives exhibited higher in vitro anti-HCV activity at low nanomolar concentrations compared to L0909. A biological study indicated that the high potency of active derivatives 3d, 3h, and 3i was primarily driven by the inhibitory effect on the virus entry stage. Moreover, an SPR experiment confirmed that this class of derivatives might target the HCV E1 protein. Pharmacokinetic studies indicated that compounds 3d and 3i are orally available and long-lasting in rat plasma after oral administration to rats by a single dose of 15 mg/kg. In conclusion, this work provided a novel 2-((4-bisarylmethyl-piperazin-1-yl)methyl)benzonitrile chemotype deserving further investigation into its antiviral therapeutic potential.

Real-Time Induction of Macrophage Apoptosis, Pyroptosis, and Necroptosis by Enterococcus faecalis OG1RF and Two Root Canal Isolated Strains.

To investigate the effects of two Enterococcus faecalis root canal isolated strains (CA1 and CA2) and of the OG1RF strain on apoptosis, pyroptosis, and necroptosis in macrophages. The virulence factors of E. faecalis CA1 and CA2 pathogenic strains were annotated in the Virulence Factors Database (VFDB). E. faecalis CA1, CA2, and OG1RF strains were used to infect RAW264.7 macrophages (MOI, 100:1). We assessed the viability of intracellular and extracellular bacteria and of macrophages at 2, 6, and 12 h post-infection. We used a live cell imaging analysis system to obtain a dynamic curve of cell death after infection by each of the three E. faecalis strains. At 6 and 12 h post-infection, we quantified the mRNA expression levels of PANoptosis-related genes and proteins by RT-qPCR and western blot, respectively. We identified ultrastructural changes in RAW264.7 cells infected with E. faecalis OG1RF using transmission electron microscopy. We found 145 and 160 virulence factors in the CA1 and CA2 strains, respectively. The extracellular CA1 strains grew faster than the CA2 and OG1RF strains, and the amount of intracellular viable bacteria in the OG1RF group was highest at 6 and 12 h post-infection. The macrophages in the CA1 infection group were the first to reach the maximum PI-positivity in the cell death time point curve. We found the expressions of mRNA expression of caspase-1, GSDMD, caspase-3, MLKL, RIPK3, NLRP3, IL-1ß and IL-18 and of proteins cleaved caspase-1, GSDMD, cleaved caspase-3 and pMIKL in the macrophages of the three infection groups to be upregulated (P<0.05). We detected ultrastructural changes of apoptosis, pyroptosis, and necroptosis in macrophages infected with E. faecalis. The three E. faecalis strains induced varying degrees of apoptosis, pyroptosis, and necroptosis that were probably associated with PANoptosis in macrophages. The E. faecalis CA1 strain exhibited faster growth and a higher real-time MOI, and it induced higher expression levels of some PANoptosis-related genes and proteins in the infected macrophages than the other strains tested.

Natural Killer-Like B Cells Secreting Interleukin-18 Induces a Proinflammatory Response in Periodontitis.

Natural killer-like B (NKB) cells, which are newly identified immune subsets, reveal a critical immunoregulatory property in the eradication of microbial infection via the secretion of interleukin (IL)-18. For the first time, this study investigated the role of NKB cells in secreting IL-18 in the pathogenesis of periodontitis. In this study, NKB cells' percentage and IL-18 concentration in peripheral blood and periodontium in periodontitis patients was measured using flow cytometry and ELISA. The role of IL-18 in regulating periodontal inflammation was examined in a Porphyromonas gingivalis (P. gingivalis)-induced periodontitis murine model. Peripheral and periodontal-infiltrating CD3-CD19+NKp46+ NKB cells, which were the main source of IL-18, were elevated and correlated with attachment loss in periodontitis patients. In vitro IL-18 stimulation promoted proinflammatory cytokine production in periodontal ligament cells. P. gingivalis infection induced elevation of IL-18 receptor in periodontium in a periodontitis murine model. IL-18 neutralization not only suppressed P. gingivalis-induced alveolar bone resorption, but also inhibited recruitment of antigen-non-specific inflammatory cells into the periodontium, probably via dampening expressions of cytokines, chemokines, and matrix metalloproteinases. NKB cells secreting IL-18 appeared to be an important mediator in the inflammatory response following intraoral P. gingivalis infection. These findings might be relevant to the development of immunotherapies for periodontitis.

TGF-ß isoforms inhibit hepatitis C virus propagation in transforming growth factor beta/SMAD protein signalling pathway dependent and independent manners.

Transforming growth factor beta (TGF-ß) plays an important role in the viral liver disease progression via controlling viral propagation and mediating inflammation-associated responses. However, the antiviral activities and mechanisms of TGF-ß isoforms, including TGF-ß1, TGF-ß2 and TGF-ß3, remain unclear. Here, we demonstrated that all of the three TGF-ß isoforms were increased in Huh7.5 cells infected by hepatitis C virus (HCV), but in turn, the elevated TGF-ß isoforms could inhibit HCV propagation with different potency in infectious HCV cell culture system. TGF-ß isoforms suppressed HCV propagation through interrupting several different stages in the whole HCV life cycle, including virus entry and intracellular replication, in TGF-ß/SMAD signalling pathway-dependent and TGF-ß/SMAD signalling pathway-independent manners. TGF-ß isoforms showed additional anti-HCV activities when combined with each other. However, the elevated TGF-ß1 and TGF-ß2, not TGF-ß3, could also induce liver fibrosis with a high expression of type I collagen alpha-1 and α-smooth muscle actin in LX-2 cells. Our results showed a new insight into TGF-ß isoforms in the HCV-related liver disease progression.

Rspo1-LGR4 axis in BMSCs protects bone against radiation-induced injury through the mTOR-dependent autophagy pathway.

While mesenchymal stem cells (MSCs) have been widely used to repair radiation-induced bone damage, the molecular mechanism underlying the effects of MSCs in the maintenance of bone homeostasis under radiation stress remains largely unknown. In this study, the role and mechanisms of R-spondin 1 (Rspo1)-leucine-rich repeat-containing G protein-coupled receptor 4 (LGR4) axis on the initiation of self-defense of bone mesenchymal stem cells (BMSCs) and maintenance of bone homeostasis under radiation stress were investigated. Interestingly, radiation increased levels of Rspo1 and LGR4 in BMSCs. siRNA knockdown of Rspo1 or LGR4 aggravated radiation-induced impairment of self-renewal ability and osteogenic differentiation potential of BMSCs. However, exogenous Rspo1 significantly attenuated radiation-induced depletion of BMSCs, and promoted the lineage shift towards osteoblasts. This alteration was associated with the reversal of mammalian target of rapamycin (mTOR) activation and autophagy decrement. Pharmacological and genetic blockade of autophagy attenuated the radio-protective effects of Rspo1, rendering BMSCs more vulnerable to radiation-induced injury. Then bone radiation injury was induced in C57BL6J mice to further determine the radio-protective effects of Rspo1. In mice, administration of Rspo1 recombinant protein alleviated radiation-induced bone loss. Our results uncover that Rspo1-LGR4-mTOR-autophagy axis are key mechanisms by which BMSCs initiate self-defense against radiation and maintain bone homeostasis. Targeting Rspo1-LGR4 may provide a novel strategy for the intervention of radiation-induced bone damage.

Sustained Release of Two Bioactive Factors from Supramolecular Hydrogel Promotes Periodontal Bone Regeneration.

Intact and stable bone reconstruction is ideal for the treatment of periodontal bone destruction but remains challenging. In research, biomaterials are used to encapsulate stem cells or bioactive factors for periodontal bone regeneration, but, to the best of our knowledge, using a supramolecular hydrogel to encapsulate bioactive factors for their sustained release in bone defect areas to promote periodontal bone regeneration has not been reported. Herein, we used a well-studied hydrogelator, NapFFY, to coassemble with SDF-1 and BMP-2 to prepare a supramolecular hydrogel, SDF-1/BMP-2/NapFFY. In vitro and in vivo results indicated that these two bioactive factors were ideally, synchronously, and continuously released from the hydrogel to effectively promote the regeneration and reconstruction of periodontal bone tissues. Specifically, after the bone defect areas were treated with our SDF-1/BMP-2/NapFFY hydrogel for 8 weeks using maxillary critical-sized periodontal bone defect model rats, a superior bone regeneration rate of 56.7% bone volume fraction was achieved in these rats. We anticipate that our SDF-1/BMP-2/NapFFY hydrogel could replace bone transplantation in the clinic for the repair of periodontal bone defects and periodontally accelerated osteogenic orthodontics in the near future.

A proof-of-concept study in HCV-infected Huh7.5 cells for shortening the duration of DAA-based triple treatment regimens.

With the development of more effective direct-acting antivirals (DAAs), dual- or triple-therapy regimens represent the major strategy used to cure chronic hepatitis C virus (HCV) infection. Thus, shorter treatment duration regimens with low burden, few adverse effects and good patient adherence are urgently needed. This study theoretically demonstrates a proof-of-concept approach for shortening therapy duration by examining HCV-infected Huh7.5 cells after treatment with a high or low fixed dose of three DAAs (simeprevir + daclatasvir + sofosbuvir) for 6-15 days. The results demonstrated that HCV-infected Huh7.5 cells achieved an ultrarapid virologic response with undetectable HCV RNA and protein and were cured after treatment with the triple-therapy regimen for 15 days. When the treatment duration was shortened, virologic relapse might occur after treatment with a low fixed dose of the three DAAs for 9 days and did occur after treatment with a low fixed dose for 6 days, although HCV was below detectable levels at the end of treatment. However, virologic relapse could be avoided with treatment of a high fixed dose of the three DAAs for 9 or 6 days. Although a virologic breakthrough occurred after an intermittent treatment regimen at the low fixed dose, the high fixed dose cured HCV-positive Huh7.5 cells with intermittent treatment. In conclusion, HCV is persistently present below detectable levels in HCV-infected Huh7.5 cells for a long time after treatment, and a shortened therapy duration is associated with an increased risk of virologic relapse, but virologic relapse or breakthrough might be avoided by treatment with a combination of more highly effective DAAs.

Raistrickindole A, an Anti-HCV Oxazinoindole Alkaloid from Penicillium raistrickii IMB17-034.

Raistrickindole A (1), a new indole diketopiperazine alkaloid containing an unusual pyrazino[1',2':2,3][1,2]oxazino[6,5- b]indole tetraheterocyclic ring system, a new benzodiazepine derivative, raistrickin (2), and the known haenamindole (3) and sclerotigenin (4) were isolated from the marine-derived fungus Penicillium raistrickii IMB17-034. Their structures were elucidated by extensive spectroscopic analyses and TDDFT calculations of the NMR and ECD data. Compounds 1 and 2 showed inhibitory activities against the hepatitis C virus.

Dysregulation of the miR-146a-Smad4 axis impairs osteogenesis of bone mesenchymal stem cells under inflammation.

Osteoporosis is a common disease that affects patient quality of life, especially among the elderly population. Although inflammation contributes significantly to osteoporosis, the underlying mechanism is unclear. In this study, we found that tumor necrosis factor (TNF)-α, an inflammatory environment mimic, inhibits osteogenesis of bone mesenchymal stem cells (BMSCs), induces miR-146a and decreases Smad4. Moreover, overexpression of miR-146a inhibited the osteogenic ability of BMSCs, whereas blocking miR-146a partially rescued the osteogenesis deficiency under TNF-α treatment. Molecularly, miR-146a decreased Smad4 expression at the protein level by binding to an element located in the Smad4 3'-untranslated region, and restoration of Smad4 reversed the inhibitory effects of miR-146a on osteogenesis. Together, our results showed that the inflammatory environment mimic TNF-α inhibits osteogenesis via upregulation of miR-146a and subsequent downregulation of Smad4, thus suggesting that therapeutic manipulation of miR-146a maybe a potential strategy to improve osteogenesis in the context of osteoporosis.

Ternary cocktail nanoparticles for sequential chemo-photodynamic therapy.

BACKGROUND: Previous clinical trials have already demonstrated that combinations of two or more drugs were more effective in the cancer treatment, especially sequential photodynamic design combing with sequential chemotherapy. In our study, we propose a ternary cocktail NP delivery system based on self-decomposable NPs, which could realize synergistic chemo-photodynamic therapy through double loading chemo-drugs and multi-level programmable PDT treatment. METHODS: PS drug methylene blue (MB) was encapsulated into the center of the NPsmall, NPbig&thin, and NPbig&thick carriers through "grown-in" loading mechanism, which was released based on the drug concentration difference of the drug release environment. NPsmall, NPbig&thin, and NPbig&thick carriers have three different drug release profiles, which could realize multi-level programmable PDT treatment. At the same time, antitumor drug gemcitabine hydrochloride (GM) and Docetaxel (DTX), were chosen as the double loading chemo-drugs that absorbed onto the NPbig&thin and NPbig&thick surface, respectively. In specific, various particle configurations were used for modulating the inner MB sequential release with three pulse Tmax. Also, by adjusting the NPbig&thin and NPbig&thick configuration, the release interval lag time between absorbed GM and DTX can be successfully modulated to achieve maximized chemotherapeutic efficacy. RESULTS: In vitro and in vivo results demonstrated that these three pulses Tmax and the sustained release of MB could maximize the multi-level programmable PDT treatment. And the absorbed GM and DTX also have a release time lag of 12 h, which has been proved as the most effectiveness synergistic interval lag time in the cancer treatment. CONCLUSION: Such a precise sequential release manner ternary cocktail NPs provided a promising platform for efficient and safe chemo-photodynamic therapy, which serves as a promising drug delivery system to cure cancer in the future.

'Osteoimmunology' Offers New Perspectives for the Treatment of Pathological Bone Loss.

New evidence of the interactions between the immune system and bone has accumulated in bone diseases, including osteoporosis, periodontitis and rheumatoid arthritis. A marked imbalance between bone resorption and formation is central to the onset of pathological bone loss. Osteoimmunology has revealed that the immune system, including T cells, B cells and inflammatory cytokines, is a key regulator of both osteoclasts and osteoblasts. Th1 cells, which differentiate from CD4+T cells, are thought to play a major function during bone loss. Moreover, the correlated expression of Th1 cytokines (interleukin-12 (IL-12), interferon-γ (IFN-γ)) and bone-resorbing cytokines (tumor necrosis factor-α (TNF-α), IL-1) also plays a key role during inflammatory induced bone resorption. Furthermore, a relatively new member of the CD4+T cell family Th17 displays the ability to promote osteoclast activity. The effect of IFN-γ and IL-17 released by Th 17 cells on pre-osteoclast proliferation, differentiation and apoptosis provides the preliminary basis for the immune mechanism of pathological bone loss. The role of B cells in osteoimmunological interactions has long been suspected based on findings of B cells as active regulators of the RANK/RANKL/OPG axis. Pathological bone loss, including osteoporosis and human immunodeficiency virus-associated bone loss, are related to the altered RANKL/OPG through modified production by B cells, supporting this assumption. All of the above evidence may provide new theoretical explanations for the relationship between bone metabolism and the immune system as well as offer perspectives for the prevention and treatment of pathological bone loss.

miR-203 inhibits cell proliferation and promotes cisplatin induced cell death in tongue squamous cancer.

Oral squamous cell carcinoma (OSCC) is one of the most common types of the head and neck cancer. Chemo resistance of OSCC has been identified as a substantial therapeutic hurdle. In this study, we analyzed the role of miR-203 in the OSCC and its effects on cisplatin-induced cell death in an OSCC cell line, Tca8113. There was a significant decrease of miR-203 expression in OSCC samples, compared with the adjacent normal, non-cancerous tissue. After 3 days cisplatin treatment, the survived Tca8113 cells had a lower expression of miR-203 than that in the untreated control group. In contrast, PIK3CA showed an inverse expression in cancer and cisplatin survived Tca8113 cells. Transfection of Tca8113 cells with miR-203 mimics greatly reduced PIK3CA expression and Akt activation. Furthermore, miR-203 repressed PIK3CA expression through targeting the 3'UTR. Restoration of miR-203 not only suppressed cell proliferation, but also sensitized cells to cisplatin induced cell apoptosis. This effect was absent in cells that were simultaneously treated with PIK3CA RNAi. In summary, these findings suggest miR-203 plays an important role in cisplatin resistance in OSCC, and furthermore delivery of miR-203 analogs may serve as an adjuvant therapy for OSCC.