Lian-Mei-Yin formula alleviates diet-induced hepatic steatosis by suppressing Yap1/FOXM1 pathway-dependent lipid synthesis.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, with a global prevalence of 25%. Patients with NAFLD are more likely to suffer from advanced liver disease, cardiovascular disease, or type II diabetes. However, unfortunately, there is still a shortage of FDA-approved therapeutic agents for NAFLD. Lian-Mei-Yin (LMY) is a traditional Chinese medicine formula used for decades to treat liver disorders. It has recently been applied to type II diabetes which is closely related to insulin resistance. Given that NAFLD is another disease involved in insulin resistance, we hypothesize that LMY might be a promising formula for NAFLD therapy. Herein, we verify that the LMY formula effectively reduces hepatic steatosis in diet-induced zebrafish and NAFLD model mice in a time- and dose-dependent manner. Mechanistically, LMY suppresses Yap1-mediated Foxm1 activation, which is crucial for the occurrence and development of NAFLD. Consequently, lipogenesis is ameliorated by LMY administration. In summary, the LMY formula alleviates diet-induced NAFLD in zebrafish and mice by inhibiting Yap1/Foxm1 signaling-mediated NAFLD pathology.

Effects of Aloe Gel on Lactating Women with Nipple Trauma.

Background: To investigate the efficacy of aloe gel in reducing pain and promoting wound healing in postpartum women with nipple trauma. Method: There were 80 postpartum women who took part in this study having developed nipple trauma during breastfeeding in the obstetrics department of a tertiary grade A hospital in Suzhou from January to December 2021. Postpartum women with nipple trauma whose hospital bed numbers ranged between 15 and 33 were included in the test group, whereas those whose hospital bed numbers ranged between 35 and 53 were included in the control group. Both groups received health education and breastfeeding guidance. The control group applied lanolin cream to their nipple trauma, whereas the test group used aloe gel. We used a nipple trauma severity assessment table to determine the severity of nipple trauma in lactating women and a Visual Analogue Scale (VAS) to determine the level of nipple pain and referred to the Traditional Chinese Medicine Standard for Diagnosis and Therapeutic Efficacy for Diseases and Syndromes to determine the healing time of their wounds. Results: The test group scored 3.70 ± 1.24 and 1.65 ± 0.74 points on the VAS on the first and third days following the intervention, whereas the control group scored 4.30 ± 0.94 and 2.23 ± 1.07 points, respectively. It took 3.75 ± 1.08 days and 4.45 ± 1.15 days for the nipple pain to completely disappear in the test group and the control group, respectively. The healing period for nipple trauma was 5.28 ± 1.26 days for the test group and 6.03 ± 1.61 days for the control group. All of the aforementioned distinctions were statistically significant (p < 0.05). Conclusions: Aloe gel can significantly alleviate the pain associated with nipple trauma in lactating women, accelerate wound healing, and reduce the duration of nipple trauma.

A universal powder-laden crosslinked chitosan microneedle patch for high-dose controllable drug delivery.

In this study, we constructed a novel powder-laden core-shell crosslinked chitosan microneedle patch for high-dose and controllable delivery of various drugs, including both macromolecular biological drugs and small-molecule chemical drugs. Direct loading of drug powders greatly improved drug loading capacity and minimized degradation. The results of the in vitro drug release study suggested that the release behaviors of the most tested drugs (both macromolecular drugs and small-molecule drugs) can be tuned by adjusting the crosslink density of the microneedle shell to achieve either rapid or sustained release of the loaded drug. The in vivo hypoglycemic efficacy test in streptozotocin-induced diabetic mice further proved that the onset and duration of the insulin-laden patch can be customized by adjusting the crosslink density. Furthermore, a combination of microneedle patches with different crosslink densities not only rapidly reduced blood glucose levels to normoglycemic levels (within 1 h) but also maintained normoglycemia for up to 36 h. The insulin loaded in the patch also showed good stability during storage at 40 °C for 6 months. Our results suggest that this powder-laden patch represents a strong candidate for addressing the multiple challenges in the preparation and application of polymeric microneedles and shows promise in clinical applications.

SAIF plays anti-angiogenesis via blocking VEGF-VEGFR2-ERK signal in tumor treatment.

Shark cartilage was created as a cancer-fighting diet because it was believed to have an element that may suppress tumor growth. Due to overfishing, sharks have become endangered recently, making it impossible to harvest natural components from shark cartilage for therapeutic development research. Previously, we identified a peptide SAIF from shark cartilage with an-tiangiogenic and anti-tumor effects, successfully expressed it in Escherichia coli by using genetic engineering techniques. However, we did not elucidate the specific target of SAIF and its antiangiogenic molecular mechanism, which hindered its further drug development. Therefore, in this work, the exact mechanism of action was studied using various techniques, including cellular and in vivo animal models, computer-aided simulation, molecular target capture, and transcriptome sequencing analysis. With VEGF-VEGFR2 interaction and preventing the activation of VEGFR2/ERK signaling pathways, SAIF was discovered to decrease angiogenesis and hence significantly limit tumor development. The findings further demonstrated SAIF's strong safety and pharmaceutically potential. The evidence showed that SAIF, which is expressed by, is a potent and safe angiogenesis inhibitor and might be developed as a candidate peptide drug for the treatment of solid tumors such as hepatocellular carcinoma and other conditions linked with angiogenic overgrowth.

Phosphorus partitioning contribute to phosphorus use efficiency during grain filling in Zea mays.

Introduction: Lower phosphorus (P) availability limits crop productivity in agroecosystems. The remobilization of P from the source to the sink organs plays an important role in enhancing the P-utilization efficiency of crops. During the grain filling stage, phosphorus flow to the developing grains, the primary sink, determines crop yield. However, the specific contributions of different organs to grain P throughout the post-silking period in maize remain unclear. Methods: In our study, three maize inbred lines (CIMBL89, Ji846, and CML118) with contrasting P statuses were selected and grown in a field with high P (HP, 150 kg ha-1 P2O5) and low P (LP, 0 kg ha-1 P2O5) conditions. Results: The grain yield of CIMBL89 was 69% and 169% greater under HP supply, and 83% and 309% greater than those of Ji846 and CML118 under LP supply, respectively. The ear length, ear diameter, and kernel row number of CML118 were lower than those of CIMBL89 and Ji846 under HP conditions. Most of the P (87%) in the grains of CIMBL89 came from P uptake at the LP supply, while almost all P (95%) came from P remobilization in various organs at the HP supply after silking. In contrast, 91% of the P found in the grain of CML118 came from P remobilization under LP supply, while 76% came from P uptake under HP supply after silking. Discussion: In conclusion, our findings suggest that CIMBL89, with greater P acquisition efficiency, contributes to grain formation and production during the post-silking period under LP conditions. Additionally, CIMBL89 can fully remobilize P and avoid the extravagant absorption of P in P-sufficient soil, which sets it apart from Ji846 and CML118.

CH02 peptide promotes ex vivo expansion of umbilical cord blood-derived CD34 + hematopoietic stem/progenitor cells.

Umbilical cord blood (UCB) is an advantageous source for hematopoietic stem/progenitor cell (HSPC) transplantation, yet the current strategies for large-scale and cost-effective UCB-HSPC preparation are still unavailable. To overcome these obstacles, we systematically evaluate the feasibility of our newly identified CH02 peptide for ex vivo expansion of CD34 + UCB-HSPCs. We herein report that the CH02 peptide is specifically enriched in HSPC proliferation via activating the FLT3 signaling. Notably, the CH02-based cocktails are adequate for boosting 12-fold ex vivo expansion of UCB-HSPCs. Meanwhile, CH02-preconditioned UCB-HSPCs manifest preferable efficacy upon wound healing in diabetic mice via bidirectional orchestration of proinflammatory and anti-inflammatory factors. Together, our data indicate the advantages of the CH02-based strategy for ex vivo expansion of CD34 + UCB-HSPCs, which will provide new strategies for further development of large-scale HSPC preparation for clinical purposes.

FGFR4 and EZH2 inhibitors synergistically induce hepatocellular carcinoma apoptosis via repressing YAP signaling.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common and lethal cancers worldwide, but current treatment options remain limited and cause serious life-threatening side effects. Aberrant FGFR4 signaling has been validated as an oncogenic driver of HCC, and EZH2, the catalytic subunit of the PRC2 complex, is a potential factor that contributes to acquired drug resistance in many tumors, including HCC. However, the functional relationship between these two carcinogenic factors, especially their significance for HCC treatment, remains unclear. In this study, we systematically evaluated the feasibility of a combination therapy targeting FGFR4 and EZH2 for HCC. METHODS: RNA sequencing data of patients with Liver hepatocellular carcinoma (LIHC) from The Cancer Genome Atlas (TCGA) were analyzed to determine FGFR4 and EZH2 expression and their interaction with prognosis. Moreover, the HCC cell lines, zebrafish/mouse HCC xenografts and zebrafish HCC primary tumors were treated with FGFR4 inhibitor (Roblitinib) and/or EZH2 inhibitor (CPI-169) and then subjected to cell proliferation, viability, apoptosis, and tumor growth analyses to evaluate the feasibility of combination therapy for HCC both in vitro and in vivo. Furthermore, RNA-Seq was performed in combination with ChIP-Seq data analysis to investigate the critical mechanism underlying the combination treatment with Roblitinib and CPI-169. RESULTS: EZH2 accumulated through the non-canonical NF-kB signaling in response to FGFR4 inhibitor treatment, and the elevated EZH2 levels led to the antagonism of HCC against Roblitinib (FGFR4 inhibitor). Notably, knockdown of EZH2 sensitized HCC cells to Roblitinib, while the combination treatment of Roblitinib and CPI-169 (EZH2 inhibitor) synergistically induced the HCC cell apoptosis in vitro and suppressed the zebrafish/mouse HCC xenografts and zebrafish HCC primary tumors development in vivo. Moreover, Roblitinib and CPI-169 synergistically inhibited HCC development via repressing YAP signaling. CONCLUSIONS: Collectively, our study highlighted the potential of the therapeutic combination of FGFR4 and EZH2 inhibitors, which would provide new references for the further development of clinical treatment strategies for HCC.

Hyaluronic acid-FGF2-derived peptide bioconjugates for suppression of FGFR2 and AR simultaneously as an acne antagonist.

Acne is a chronic skin condition that has serious consequences for mental and social well-being because it frequently occurs on the face. Several acne treatment approaches have commonly been used but have been hampered by side effects or weak activity. Thus, the investigation of the safety and efficacy of anti-acne compounds is of considerable medical importance. Herein, an endogenous peptide (P5) derived from fibroblast growth factors 2 (FGF2) was conjugated to the polysaccharide hyaluronic acid (HA) to generate the bioconjugate nanoparticle HA-P5, which suppresses fibroblast growth factor receptors (FGFRs) to significantly rehabilitate acne lesions and reduce sebum accumulation in vivo and in vitro. Moreover, our results show that HA-P5 inhibits both fibroblast growth factor receptor 2 (FGFR2) and androgen receptor (AR) signalling in SZ95 cells, reverses the acne-prone transcriptome, and decreases sebum secretion. Furthermore, the cosuppression mechanism revealed that HA-P5 blocks FGFR2 activation, as well as the YTH N6-methyladenosine RNA binding protein F3 (YTHDF3) downstream molecules, including an N6-methyladenosine (m6A) reader that facilitates AR translation. More importantly, a significant difference between HA-P5 and the commercial FGFR inhibitor AZD4547 is that HA-P5 does not trigger the overexpression of aldo-keto reductase family 1 member C3 (AKR1C3), which blocks acne treatment by catalyzing the synthesis of testosterone. Overall, we demonstrate that a polysaccharide-conjugated and naturally derived oligopeptide HA-P5 can alleviate acne and act as an optimal FGFR2 inhibitor and reveal that YTHDF3 plays a crucial role in signalling between FGFR2 and AR.

Two-sample Behrens-Fisher problems for high-dimensional data: a normal reference scale-invariant test.

For high-dimensional two-sample Behrens-Fisher problems, several non-scale-invariant and scale-invariant tests have been proposed. Most of them impose strong assumptions on the underlying group covariance matrices so that their test statistics are asymptotically normal. However, in practice, these assumptions may not be satisfied or hardly be checked so that these tests may not be able to maintain the nominal size well in practice. To overcome this difficulty, in this paper, a normal reference scale-invariant test is proposed and studied. It works well by neither imposing strong assumptions on the underlying group covariance matrices nor assuming their equality. It is shown that under some regularity conditions and the null hypothesis, the proposed test and a chi-square-type mixture have the same normal and non-normal limiting distributions. It is then justifiable to approximate the null distribution of the proposed test using that of the chi-square-type mixture. The distribution of the chi-square type mixture can be well approximated by the Welch-Satterthwaite chi-square-approximation with the approximation parameter consistently estimated from the data. The asymptotic power of the proposed test is established. Numerical results demonstrate that the proposed test has much better size control and power than several well-known non-scale-invariant and scale-invariant tests.

Determining Association between Lung Cancer Mortality Worldwide and Risk Factors Using Fuzzy Inference Modeling and Random Forest Modeling.

Lung cancer remains the leading cause for cancer mortality worldwide. While it is well-known that smoking is an avoidable high-risk factor for lung cancer, it is necessary to identify the extent to which other modified risk factors might further affect the cell's genetic predisposition for lung cancer susceptibility, and the spreading of carcinogens in various geographical zones. This study aims to examine the association between lung cancer mortality (LCM) and major risk factors. We used Fuzzy Inference Modeling (FIM) and Random Forest Modeling (RFM) approaches to analyze LCM and its possible links to 30 risk factors in 100 countries over the period from 2006 to 2016. Analysis results suggest that in addition to smoking, low physical activity, child wasting, low birth weight due to short gestation, iron deficiency, diet low in nuts and seeds, vitamin A deficiency, low bone mineral density, air pollution, and a diet high in sodium are potential risk factors associated with LCM. This study demonstrates the usefulness of two approaches for multi-factor analysis of determining risk factors associated with cancer mortality.

Predict Health Care Accessibility for Texas Medicaid Gap.

Medicaid is a unique approach in ensuring the below poverty population obtains free insurance coverage under federal and state provisions in the United States. Twelve states without expanded Medicaid caused two million people who were under the poverty line into health insecurity. Principal Component-based logistical regression (PCA-LA) is used to consider health status (HS) as a dependent variable and fourteen social-economic indexes as independent variables. Four composite components incorporated health conditions (i.e., "no regular source of care" (NRC), "last check-up more than a year ago" (LCT)), demographic impacts (i.e., four categorized adults (AS)), education (ED), and marital status (MS). Compared to the unadjusted LA, direct adjusted LA, and PCA-unadjusted LA three methods, the PCA-LA approach exhibited objective and reasonable outcomes in presenting an odd ratio (OR). They included that health condition is positively significant to HS due to beyond one OR, and negatively significant to ED, AS, and MS. This paper provided quantitative evidence for the Medicaid gap in Texas to extend Medicaid, exposed healthcare geographical inequity, offered a sight for the Centers for Disease Control and Prevention (CDC) to improve the Medicaid program and make political justice for the Medicaid gap.

Space-Time Cluster's Detection and Geographical Weighted Regression Analysis of COVID-19 Mortality on Texas Counties.

As COVID-19 run rampant in high-density housing sites, it is important to use real-time data in tracking the virus mobility. Emerging cluster detection analysis is a precise way of blunting the spread of COVID-19 as quickly as possible and save lives. To track compliable mobility of COVID-19 on a spatial-temporal scale, this research appropriately analyzed the disparities between spatial-temporal clusters, expectation maximization clustering (EM), and hierarchical clustering (HC) analysis on Texas county-level. Then, based on the outcome of clustering analysis, the sensitive counties are Cottle, Stonewall, Bexar, Tarrant, Dallas, Harris, Jim hogg, and Real, corresponding to Southeast Texas analysis in Geographically Weighted Regression (GWR) modeling. The sensitive period took place in the last two quarters in 2020 and the first quarter in 2021. We explored PostSQL application to portray tracking Covid-19 trajectory. We captured 14 social, economic, and environmental impact's indices to perform principal component analysis (PCA) to reduce dimensionality and minimize multicollinearity. By using the PCA, we extracted five factors related to mortality of COVID-19, involved population and hospitalization, adult population, natural supply, economic condition, air quality or medical care. We established the GWR model to seek the sensitive factors. The result shows that adult population, economic condition, air quality, and medical care are the sensitive factors. Those factors also triggered high increase of COVID-19 mortality. This research provides geographical understanding and solution of controlling COVID-19, reference of implementing geographically targeted ways to track virus mobility, and satisfy for the need of emergency operations plan (EOP).

Spatio-temporal characteristics and control strategies in the early period of COVID-19 spread: a case study of the mainland China.

COVID-19 has caused huge impacts on human health and the economic operation of the world. Analyzing and summarizing the early propagation law can help reduce the losses caused by public health emergencies in the future. Early data on the spread of COVID-19 in 30 provinces (autonomous regions and municipalities) of mainland China except for Hubei, Hong Kong, Macao, and Taiwan were selected in this study. Spatio-temporal analysis, inflection point analysis, and correlation analysis are used to explore the spatio-temporal characteristics in the early COVID-19 spread. The results suggested that (1) the total confirmed cases have risen in an "S"-shaped curve over time, and the daily new cases have first increased and finally decreased; (2) the spatial distributions of both total and daily new cases show a trend of more in the east and less in the west, with a "multi-center agglomeration distribution" around Hubei Province and some major cities; (3) the spatial agglomeration of total confirmed cases has been increasing over time, while that of the daily new cases shows much more obvious in the mid-stage; and (4) timely release of the first-level public health emergency response can accelerate the emergence of the epidemic inflection point. The above analysis results have a specific reference value for the government's policy-making and measures to face public health emergencies.

Exploration of spatial-temporal varying impacts on COVID-19 cumulative case in Texas using geographically weighted regression (GWR).

Since COVID-19 is extremely threatening to human health, it is significant to determine its impact factors to curb the virus spread. To tackle the complexity of COVID-19 expansion on a spatial-temporal scale, this research appropriately analyzed the spatial-temporal heterogeneity at the county-level in Texas. First, the impact factors of COVID-19 are captured on social, economic, and environmental multiple facets, and the communality is extracted through principal component analysis (PCA). Second, this research uses COVID-19 cumulative case as the dependent variable and the common factors as the independent variables. According to the virus prevalence hierarchy, the spatial-temporal disparity is categorized into four quarters in the GWR analysis model. The findings exhibited that GWR models provide higher fitness and more geodata-oriented information than OLS models. In El Paso, Odessa, Midland, Randall, and Potter County areas in Texas, population, hospitalization, and age structures are presented as static, positive influences on COVID-19 cumulative cases, indicating that they should adopt stringent strategies in curbing COVID-19. Winter is the most sensitive season for the virus spread, implying that the last quarter should be paid more attention to preventing the virus and taking precautions. This research is expected to provide references for the prevention and control of COVID-19 and related infectious diseases and evidence for disease surveillance and response systems to facilitate the appropriate uptake and reuse of geographical data.

Nanomorphological and mechanical reconstruction of mesenchymal stem cells during early apoptosis detected by atomic force microscopy.

Stem cell apoptosis exists widely in embryonic development, tissue regeneration, repair, aging and pathophysiology of disease. The molecular mechanism of stem cell apoptosis has been extensively investigated. However, alterations in biomechanics and nanomorphology have rarely been studied. Therefore, an apoptosis model was established for bone marrow mesenchymal stem cells (BMSCs) and the reconstruction of the mechanical properties and nanomorphology of the cells were investigated in detail. Atomic force microscopy (AFM), scanning electron microscopy (SEM), laser scanning confocal microscopy (LSCM), flow cytometry and Cell Counting Kit-8 analysis were applied to assess the cellular elasticity modulus, geometry, nanomorphology, cell surface ultrastructure, biological viability and early apoptotic signals (phosphatidylserine, PS). The results indicated that the cellular elastic modulus and volume significantly decreased, whereas the cell surface roughness obviously increased during the first 3 h of cytochalasin B (CB) treatment. Moreover, these alterations preceded the exposure of biological apoptotic signal PS. These findings suggested that cellular mechanical damage is connected with the apoptosis of BMSCs, and the alterations in mechanics and nanomorphology may be a sensitive index to detect alterations in cell viability during apoptosis. The results contribute to further understanding of apoptosis from the perspective of cell mechanics.

[Ten-year changes in pathogen, antimicrobial susceptibility and clinical feature of children with bacterial meningitis].

OBJECTIVE: Despite progress in antibiotic therapy and intensive care, childhood bacterial meningitis (BM) remains a devastating disease. We conducted this study to investigate the changes in clinical characteristics, the etiologic agents and antimicrobial susceptibility of BM during the past 10 years in children under 14 years of age. METHODS: These 126 patients were divided into two groups according to their date of admission. Group 1 included 64 patients admitted from January 1998 to December 2002, and group 2 included 62 cases admitted from January 2003 to December 2007. All pediatric medical charts of them were reviewed. RESULTS: The predominant isolated bacteria from CSF were coagulase-negative staphylococcus (17/62, 27.4%) and Escherichia coli (9/62, 14.5%) in group 2. The resistance rate of staphylococcus against oxacillin (MRS) was 68.4% (13/19) in group 2, significantly higher than that of group 1 (16.7%, 2/12). Among 126 cases, 42 had seizure attack and 16 had consciousness disturbance, the proportions of them in group 2 (11/62, 17.7%; 4/62, 6.4%) were lower than those in group 1 (31/64, 48.4%; 12/64, 18.8%, P < 0.05). Cases in group 2 survived with complications [13/62 (21.0%)] and sequelae [11/62 (17.7%)] were lower than those in group 1 (24/64, 37.5%, 23/64, 35.9%, P < 0.05), but the rate of empirical therapy modification in group 2 (21/62, 33.9%) was higher than that in group 1 (7/64, 10.9%, P < 0.01). CONCLUSION: The predominant bacteria in children with BM are staphylococcus and Escherichia coli in recent years. The antibiotic resistance rate of bacteria has been higher year after year. The clinical patterns of pediatric BM have changed with a decrease in clinically serious cases, complications and sequelae, but an increase in modification of empirical therapy.

PINCH expression and its significance in esophageal squamous cell carcinoma.

Particularly interesting new cysteine-histidine rich protein (PINCH), as a newly discovered protein of LIM family members, may play a role in signal transduction of integrin and growth factor, and involved in the incidence and development of tumors. PINCH protein is overexpressed in tumor-associated stroma of several types of tumors. However, there is no study of the PINCH in esophageal cancer, therefore we investigated PINCH expression in esophageal squamous cell carcinomas and its clinicopathological significance in the patients. PINCH expression was immunohistochemically examined in 20 normal esophageal samples and 64 esophageal squamous cell carcinomas. The results showed that PINCH expression in the stroma of cancers was heterogeneous, and its positive rate (56%) was higher than that of normal esophageal mucosa (5%, p<0.0001). The stronger staining was observed at the invasive edge of tumor when compared to the inner area of tumor. The rate of positive PINCH (90%) in the cases with lymph node metastasis was higher than that (41%) in the cases without metastasis (p<0.0001). PINCH expression was not correlated with patients' gender, age, tumor location, size and differentiation (p>0.05). The results suggest that PINCH protein may be a marker of tumor associated-stroma involving tumor development, and predicting the ability of invasion and metastasis of esophageal squamous cell carcinoma.

Nuclear to cytoplasmic shift of p33(ING1b) protein from normal oral mucosa to oral squamous cell carcinoma in relation to clinicopathological variables.

PURPOSE: p33(ING1b), as a candidate tumour suppressor gene, has been found to be expressed a proportion of oral squamous cell carcinomas (OSCCs), however, its clinicopathological significance is not studied yet. Our aim was to investigate association of p33(ING1b) expression with clinicopathological variables and particularly interesting new cysteine-histidine rich protein (PINCH) in OSCCs. METHODS: p33(ING1b) expression was immunohistochemically examined in 20 normal oral mucosa specimens and 49 OSCCs. RESULTS: Normal squamous cells showed only p33(ING1b )nuclear expression (no cytoplasmic expression), with a rate of 90% positive cases. While 24% of OSCCs appeared cytoplasmic expression (11 of them with weak nuclear staining) and the rest tumours (76%) were negative for p33(ING1b). Furthermore, the cases having lymph node metastasis showed a higher frequency of positive cytoplasmic expression than those without metastasis (P = 0.03). The p33(ING1b) cytoplasmic expression was positively related to PINCH expression (P = 0.04), the cases positive for both proteins had a high rate of the metastasis (P = 0.03). CONCLUSIONS: The transfer of p33(ING1b) protein from the nucleus to the cytoplasm may result in loss of normal cellular function of the protein, which might play a role in the tumourigenesis and metastasis of OSCCs.

Up-regulation of PINCH in the stroma of oral squamous cell carcinoma predicts nodal metastasis.

Particularly interesting new cysteine-histidine rich protein (PINCH), an adapter protein involved in integrin and growth factor signalling, is up-regulated in the stroma of colorectal, breast, prostate, lung and skin cancer. Strong stromal immunostaining for PINCH is an independent prognostic indicator for reduced survival in colorectal cancer, suggesting that PINCH is involved in the signalling that promotes tumour progression. Since no study on PINCH has been carried out in oral squamous cell carcinoma (OSCC), this study aimed to determine PINCH expression in OSCC and its clinicopathological significance. PINCH protein expression was examined by immunohistochemistry in 20 normal oral mucosa and in 57 OSCC specimens. The frequency of strong PINCH immunostaining was higher in tumour-associated stroma of OSCC (37%) as compared to normal oral mucosa (10%) (p=0.02). Strong PINCH stromal immunostaining predicted nodal metastasis: 19/26 (73%) OSCC cases with nodal metastasis had strong PINCH immunostaining compared to 9/31 (29%) cases without nodal metastasis (p=0.02). The PINCH expression in OSCC was more intense in stroma at the invasive edge than in intratumoural stroma. In conclusion, the up-regulation of PINCH protein in stroma may be involved in promoting invasion and metastasis in OSCC.