Comprehensive multiscale analysis of lactate metabolic dynamics in vitro and in vivo using highly responsive biosensors.

As a key glycolytic metabolite, lactate has a central role in diverse physiological and pathological processes. However, comprehensive multiscale analysis of lactate metabolic dynamics in vitro and in vivo has remained an unsolved problem until now owing to the lack of a high-performance tool. We recently developed a series of genetically encoded fluorescent sensors for lactate, named FiLa, which illuminate lactate metabolism in cells, subcellular organelles, animals, and human serum and urine. In this protocol, we first describe the FiLa sensor-based strategies for real-time subcellular bioenergetic flux analysis by profiling the lactate metabolic response to different nutritional and pharmacological conditions, which provides a systematic-level view of cellular metabolic function at the subcellular scale for the first time. We also report detailed procedures for imaging lactate dynamics in live mice through a cell microcapsule system or recombinant adeno-associated virus and for the rapid and simple assay of lactate in human body fluids. This comprehensive multiscale metabolic analysis strategy may also be applied to other metabolite biosensors using various analytic platforms, further expanding its usability. The protocol is suited for users with expertise in biochemistry, molecular biology and cell biology. Typically, the preparation of FiLa-expressing cells or mice takes 2 days to 4 weeks, and live-cell and in vivo imaging can be performed within 1-2 hours. For the FiLa-based assay of body fluids, the whole measuring procedure generally takes ~1 min for one sample in a manual assay or ~3 min for 96 samples in an automatic microplate assay.

Skeletal muscle-specific DJ-1 ablation-induced atrogenes expression and mitochondrial dysfunction contributing to muscular atrophy.

BACKGROUND: DJ-1 is a causative gene for Parkinson's disease. DJ-1-deficient mice develop gait-associated progressive behavioural abnormalities and hypoactive forearm grip strength. However, underlying activity mechanisms are not fully explored. METHODS: Western blotting and quantitative real-time polymerase chain reaction approaches were adopted to analyse DJ-1 expression in skeletal muscle from aged humans or mice and compared with young subjects. Skeletal muscle-specific-DJ-1 knockout (MDKO) mice were generated, followed by an assessment of the physical activity phenotypes (grip strength, maximal load capacity, and hanging, rotarod, and exercise capacity tests) of the MDKO and control mice on the chow diet. Muscular atrophy phenotypes (cross-sectional area and fibre types) were determined by imaging and quantitative real-time polymerase chain reaction. Mitochondrial function and skeletal muscle morphology were evaluated by oxygen consumption rate and electron microscopy, respectively. Tail suspension was applied to address disuse atrophy. RNA-seq analysis was performed to indicate molecular changes in muscles with DJ-1 ablation. Dual-luciferase reporter assays were employed to identify the promoter region of Trim63 and Fbxo32 genes, which were indirectly regulated by DJ-1 via the FoxO1 pathway. Cytoplasmic and nuclear fractions of DJ-1-deleted muscle cells were analysed by western blotting. Compound 23 was administered into the gastrocnemius muscle to mimic the of DJ-1 deletion effects. RESULTS: DJ-1 expression decreased in atrophied muscles of aged human (young men, n = 2; old with aged men, n = 2; young women, n = 2; old with aged women, n = 2) and immobilization mice (n = 6, P < 0.01). MDKO mice exhibited no body weight difference compared with control mice on the chow diet (Flox, n = 8; MDKO, n = 9). DJ-1-deficient muscles were slightly dystrophic (Flox, n = 7; MDKO, n = 8; P < 0.05), with impaired physical activities and oxidative capacity (n = 8, P < 0.01). In disuse-atrophic conditions, MDKO mice showed smaller cross-sectional area (n = 5, P < 0.01) and more central nuclei than control mice (Flox, n = 7; MDKO, n = 6; P < 0.05), without alteration in muscle fibre types (Flox, n = 6; MDKO, n = 7). Biochemical analysis indicated that reduced mitochondrial function and upregulated of atrogenes induced these changes. Furthermore, RNA-seq analysis revealed enhanced activity of the FoxO1 signalling pathway in DJ-1-ablated muscles, which was responsible for the induction of atrogenes. Finally, compound 23 (an inhibitor of DJ-1) could mimic the effects of DJ-1 ablation in vivo. CONCLUSIONS: Our results illuminate the crucial of skeletal muscle DJ-1 in the regulation of catabolic signals from mechanical stimulation, providing a therapeutic target for muscle wasting diseases.

PARP1 inhibition enhances reactive oxygen species on gut microbiota.

Poly(ADP-ribose) polymerase 1 (PARP1) plays a key role in genome stability by modulating DNA-damage responses. Activated by DNA interruptions through ultraviolet (UV) exposure, PARylation is synthesized by PARP1 and serves as a survival mechanism for cancer and metabolic diseases. Several strategies including ROS and antimicrobial peptides (AMPs) function in host defenses, while the targeted tissue and mechanism under DNA damage are unknown. Here, we show that DNA damage induces responses specifically in the gut tissue. The knockdown of PARP1 reduces the activation of PARylation. Parp1 knockdown under DNA damage results in over-accumulated ROS and secretion of AMPs through the regulation of Relish, a subunit of nuclear factor-κB (NF-κB). Double-knockdown of Parp1 and Relish specifically in the gut inhibits AMP secretion. In conclusion, the host defense is achieved through ROS accumulation rather than the AMPs under DNA damage. In contrast, the knockdown of PARP1 exacerbates ROS accumulation to a harmful level. Under this circumstance, NF-κb targeted AMP secretion is provoked for host defense. Microbiome and functional analysis provide evidence for the hazard of DNA damage and show variations in the metabolic pathways following Parp1 inhibition. Our findings suggest the notion that PARP1 inhibition contributes to ROS accumulation under DNA damage and its role in NF-κb activation for host defense.

The hypothalamus for whole-body physiology: from metabolism to aging.

Obesity and aging are two important epidemic factors for metabolic syndrome and many other health issues, which contribute to devastating diseases such as cardiovascular diseases, stroke and cancers. The brain plays a central role in controlling metabolic physiology in that it integrates information from other metabolic organs, sends regulatory projections and orchestrates the whole-body function. Emerging studies suggest that brain dysfunction in sensing various internal cues or processing external cues may have profound effects on metabolic and other physiological functions. This review highlights brain dysfunction linked to genetic mutations, sex, brain inflammation, microbiota, stress as causes for whole-body pathophysiology, arguing brain dysfunction as a root cause for the epidemic of aging and obesity-related disorders. We also speculate key issues that need to be addressed on how to reveal relevant brain dysfunction that underlines the development of these disorders and diseases in order to develop new treatment strategies against these health problems.

Proteomics and Organoid Culture Reveal the Underlying Pathogenesis of Hashimoto's Thyroiditis.

Hashimoto's thyroiditis (HT) is an autoimmune disease, and its incidence continues to rise. Although scientists have studied this disease for many years and discovered the potential effects of various proteins in it, the specific pathogenesis is still not fully comprehended. To understand HT and translate this knowledge to clinical applications, we took the mass spectrometric analysis on thyroid tissue fine-needle puncture from HT patients and healthy people in an attempt to make a further understanding of the pathogenesis of HT. A total of 44 proteins with differential expression were identified in HT patients, and these proteins play vital roles in cell adhesion, cell metabolism, and thyroxine synthesis. Combining patient clinical trial sample information, we further compared the transient changes of gene expression regulation in HT and papillary thyroid carcinoma (PTC) samples. More importantly, we developed patient-derived HT and PTC organoids as a promising new preclinical model to verify these potential markers. Our data revealed a marked characteristic of HT organoid in upregulating chemokines that include C-C motif chemokine ligand (CCL) 2 and CCL3, which play a key role in the pathogenesis of HT. Overall, our research has enriched everyone's understanding of the pathogenesis of HT and provides a certain reference for the treatment of the disease.

Central 5-HTR2C in the Control of Metabolic Homeostasis.

The 5-hydroxytryptamine 2C receptor (5-HTR2C) is a class G protein-coupled receptor (GPCR) enriched in the hypothalamus and the brain stem, where it has been shown to regulate energy homeostasis, including feeding and glucose metabolism. Accordingly, 5-HTR2C has been the target of several anti-obesity drugs, though the associated side effects greatly curbed their clinical applications. Dissecting the specific neural circuits of 5-HTR2C-expressing neurons and the detailed molecular pathways of 5-HTR2C signaling in metabolic regulation will help to develop better therapeutic strategies towards metabolic disorders. In this review, we introduced the regulatory role of 5-HTR2C in feeding behavior and glucose metabolism, with particular focus on the molecular pathways, neural network, and its interaction with other metabolic hormones, such as leptin, ghrelin, insulin, and estrogens. Moreover, the latest progress in the clinical research on 5-HTR2C agonists was also discussed.

Transient Receptor Potential Ankyrin Type-1 Channels as a Potential Target for the Treatment of Cardiovascular Diseases.

Cardiovascular disease is one of the chronic conditions with the highest mortality rate in the world. Underlying conditions such as hypertension, metabolic disorders, and habits like smoking are contributors to the manifestation of cardiovascular diseases. The treatment of cardiovascular diseases is inseparable from the development of drugs. Consequently, this has led to many researchers to focus on the search for effective drug targets. The transient receptor potential channel Ankyrin 1 (TRPA1) subtype is a non-selective cation channel, which belongs to the transient receptor potential (TRP) ion channel. Previous studies have shown that members of the TRP family contribute significantly to cardiovascular disease. However, many researchers have not explored the role of TRPA1 as a potential target for the treatment of cardiovascular diseases. Furthermore, recent studies revealed that TRPA1 is commonly expressed in the vascular endothelium. The endothelium is linked to the causes of some cardiovascular diseases, such as atherosclerosis, myocardial fibrosis, heart failure, and arrhythmia. The activation of TRPA1 has a positive effect on atherosclerosis, but it has a negative effect on other cardiovascular diseases such as myocardial fibrosis and heart failure. This review introduces the structural and functional characteristics of TRPA1 and its importance on vascular physiology and common cardiovascular diseases. Moreover, this review summarizes some evidence that TRPA1 is correlated to cardiovascular disease risk factors.

Impacts of exercise interventions on different diseases and organ functions in mice.

Background: In recent years, much evidence has emerged to indicate that exercise can benefit people when performed properly. This review summarizes the exercise interventions used in studies involving mice as they are related to special diseases or physiological status. To further understand the effects of exercise interventions in treating or preventing diseases, it is important to establish a template for exercise interventions that can be used in future exercise-related studies. Methods: PubMed was used as the data resource for articles. To identify studies related to the effectiveness of exercise interventions for treating various diseases and organ functions in mice, we used the following search language: (exercise [Title] OR training [Title] OR physical activity [Title]) AND (mice [title/abstract] OR mouse [title/abstract] OR mus [title/abstract]). To limit the range of search results, we included 2 filters: one that limited publication dates to "in 10 years" and one that sorted the results as "best match". Then we grouped the commonly used exercise methods according to their similarities and differences. We then evaluated the effectiveness of the exercise interventions for their impact on diseases and organ functions in 8 different systems. Results: A total of 331 articles were included in the analysis procedure. The articles were then segmented into 8 systems for which the exercise interventions were used in targeting and treating disorders: motor system (60 studies), metabolic system (45 studies), cardio-cerebral vascular system (58 studies), nervous system (74 studies), immune system (32 studies), respiratory system (7 studies), digestive system (1 study), and the system related to the development of cancer (54 studies). The methods of exercise interventions mainly involved the use of treadmills, voluntary wheel-running, forced wheel-running, swimming, and resistance training. It was found that regardless of the specific exercise method used, most of them demonstrated positive effects on various systemic diseases and organ functions. Most diseases were remitted with exercise regardless of the exercise method used, although some diseases showed the best remission effects when a specific method was used. Conclusion: Our review strongly suggests that exercise intervention is a cornerstone in disease prevention and treatment in mice. Because exercise interventions in humans typically focus on chronic diseases, national fitness, and body weight loss, and typically have low intervention compliance rates, it is important to use mice models to investigate the molecular mechanisms underlying the health benefits from exercise interventions in humans.

Ginsenoside Rg1 supplementation clears senescence-associated ß-galactosidase in exercising human skeletal muscle.

BACKGROUND: Ginsenoside Rg1 has been shown to clear senescence-associated beta-galactosidase (SA-ß-gal) in cultured cells. It remains unknown whether Rg1 can influence SA-ß-gal in exercising human skeletal muscle. METHODS: To examine SA-ß-gal change, 12 young men (age 21 ± 0.2 years) were enrolled in a randomized double-blind placebo controlled crossover study, under two occasions: placebo (PLA) and Rg1 (5 mg) supplementations 1 h prior to a high-intensity cycling (70% VO2max). Muscle samples were collected by multiple biopsies before and after cycling exercise (0 h and 3 h). To avoid potential effect of muscle biopsy on performance assessment, cycling time to exhaustion test (80% VO2max) was conducted on another 12 participants (age 23 ± 0.5 years) with the same experimental design. RESULTS: No changes of SA-ß-gal were observed after cycling in the PLA trial. On the contrary, nine of the 12 participants showed complete elimination of SA-ß-gal in exercised muscle after cycling in the Rg1 trial (p < 0.05). Increases in apoptotic DNA fragmentation (PLA: +87% vs. Rg1: +133%, p < 0.05) and CD68+ (PLA: +78% vs. Rg1: +121%, p = 0.17) occurred immediately after cycling in both trials. During the 3-h recovery, reverses in apoptotic nuclei content (PLA: +5% vs. Rg1: -32%, p < 0.01) and increases in inducible nitrate oxide synthase and interleukin 6 mRNA levels of exercised muscle were observed only in the Rg1 trial (p < 0.01). CONCLUSION: Rg1 supplementation effectively eliminates senescent cells in exercising human skeletal muscle and improves high-intensity endurance performance.

Combined application of Embelin and tumor necrosis factor-related apoptosis-inducing ligand inhibits proliferation and invasion in osteosarcoma cells via caspase-induced apoptosis.

Embelin, as an inhibitor of the X-linked inhibitor of apoptosis protein (XIAP), may induce apoptosis in various types of cancer cells. The present study aimed to determine the effect of Embelin on the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis of osteosarcoma cells. Embelin and TRAIL were applied to U2OS and MG63 cells, respectively or in combination. MTT was initially used to detect the difference in survival rates between the group receiving combined application of 100 ng/ml TRAIL and 20 µmol/l Embelin and the individual application groups. Light microscopic quantification was used to detect the morphology of the osteosarcoma cells in each group. Determination of cell apoptosis was subsequently performed using flow cytometry. The invasive ability of the cells was detected by a Transwell assay, prior to relative protein expression being determined by western blot analysis. Based on all the test data, it was revealed that the survival rates and the invasive ability were significantly lower following the combined application of 100 ng/ml TRAIL and 20 µmol/l Embelin than following the individual application of either (P<0.01). Additionally, upregulating expression of caspases, as well as death receptor 5, and downregulating expression of XIAP and matrix metalloproteinase 9 (MMP-9), had more significant effects in the combined group compared with the individual group and the control group. All these results suggested that Embelin may enhance TRAIL-induced apoptosis and inhibit the invasion of human osteosarcoma cells.

Mean Platelet Volume and Platelet Distribution Width Are Associated with Gallbladder Cancer

Gallbladder cancer (GBC) represents the most common biliary tract malignancy. Activated platelets play an essential role in cancer development and progression. Mean platelet volume (MPV) and platelet distribution width (PDW) are commonly used indexes of activated platelets in clinical practice. The aim of the current study was to investigate the association of MPV and PDW with GBC. 104 GBC patients and 109 normal control subjects were entered in this study between January 2015 and December 2015. We collected all participants' clinical and laboratory characteristics at initial diagnosis. The odds ratios (ORs) for GBC were calculated using multivariate logistic regression analysis after adjusting for confounding variables across MPV and PDW quartiles. MPV levels were markedly lower and PDW levels were remarkably higher in GBC patients than control subjects. A significant correlation between PDW and lymph node metastasis was detected. In addition, after adjusting for other risk factors, the ORs (95% CIs) for GBC in each MPV quartile were 5.117 (1.939-13.506), 2.444 (0.917-6.516), 3.718 (1.381-10.007), and 1.000, respectively. The ORs (95% CIs) for GBC in each PDW quartile were 1.000, 2.063 (0.825-5.162), 3.070 (1.108-8.507), and 12.108 (4.243-34.553), respectively. In conclusion, decreased MPV and elevated PDW were independently associated with GBC. Our findings suggest that MPV and PDW are available parameters for early detection of GBC.

Mean platelet volume, platelet distribution width and carcinoembryonic antigen to discriminate gastric cancer from gastric ulcer.

Activated platelets are involved in cancer development and progression. Mean platelet volume (MPV) and platelet distribution width (PDW) are early indexes of platelet activation. The objectives of this study were to investigate the ability of MPV, PDW and carcinoembryonic antigen (CEA) individually or in combination, to distinguish between gastric cancer and gastric ulcer. The study involved 194 patients with gastric cancer, 191 patients with gastric ulcer, and 185 control subjects. Subjects' characteristics and hematologic tests data at initial diagnosis were collected. We found that MPV levels are significantly increased and PDW levels are significantly reduced in patients with gastric ulcer and in control subjects compared with those in gastric cancer. When the area under the curve (AUC) was used to analyze control subjects versus gastric cancer, the combination of PDW and CEA exhibited a significantly larger AUC of 0.939 (0.910-0.961) compared with the combination of MPV and CEA (p = 0.0045). When AUC was used to analyze gastric ulcer versus gastric cancer, PDW alone had the high specificity (98.5%) and high sensitivity (97.4%). In conclusion, combined use of MPV, PDW and CEA can accurately distinguish gastric cancer from gastric ulcer and controls. Further studies in larger samples are warranted.

Cancer antigen 15-3, platelet distribution width, and fibrinogen in combination to distinguish breast cancer from benign breast disease in non-conclusive mammography patients.

Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death among females. However, mammographic diagnosis is sometimes non-conclusive with a Breast imaging Reporting and Data System (Bi-RaDS) result of 0. Cancer antigen 15-3 (CA15-3) is the most widely used serum tumor marker for breast cancer screening. Platelet distribution width (PDW) is an early indicator of platelet activation. Fibrinogen contributed to angiogenesis and distant metastasis. The aim of this study was to investigate the ability of CA15-3, PDW, and fibrinogen individually or in combination, to distinguish breast cancer from benign breast disease. 200 consecutive patients with breast cancer and 187 patients with benign breast disease were included in this retrospective study. Patients' characteristics and hematologic tests data at initial diagnosis were collected. The benefit of adding PDW and fibrinogen to a model with only CA15-3 was evaluated as an increased in the area under the curve (AUC) obtained by receiver operating curve (ROC). CA15-3, PDW and fibrinogen are higher in breast cancer patients than in patients with benign breast disease. Single biomarkers had AUC values ranging from 0.687 for fibrinogen to 0.810 for CA15-3. In addition, the combination of PDW, CA15-3, and fibrinogen increased the AUC to 0.900 (0.866-0.928) (p<0.0001), significantly higher than those of any single marker. In conclusion, the combined use of CA15-3, PDW and fibrinogen may be clinically useful in discriminating between breast cancer and benign breast disease in non-conclusive mammography patients.

Decreased mean platelet volume predicts poor prognosis in invasive bladder cancer.

BACKGROUND: Altered mean platelet volume (MPV) is implicated in a wide range of cancers. However, the prognostic role of MPV in muscle-invasive bladder cancer (MIBC) remains largely unknown. The purpose of this study was to elucidate the predictive significance of MPV in MIBC. METHOD: The retrospective study included 218 consecutive MIBC patients between January 2009 and December 2009. The relationships between MPV and clinicopathological characteristics were analyzed. Kaplan-Meier method and Cox regression were used to evaluate the prognostic impact of MPV. RESULT: Of the 218 patients, low MPV levels were detected in 141 (64.7 %) patients. Reduced MPV was associated with T stage and histology grade (p < 0.05). In the Kaplan-Meier analysis, decreased MPV was significantly associated with a poorer overall survival (p = 0.007). In the multivariate Cox model, decreased MPV was an independent prognostic index for overall survival (HR=2.023, 95% CI=1.050-3.897, p = 0.025). CONCLUSION: MPV is easily available in routine blood test. Our results demonstrated that reduced MPV could be regarded as a potential prognosis indicator for clinical outcome in MIBC.

Elevated mean platelet volume predicts poor prognosis in colorectal cancer.

Altered mean platelet volume (MPV) is implicated in several malignancies. However, the clinicopathological significance and prognostic value of MPV in colorectal cancer (CRC) is still elusive. The purpose of this study was to elucidate the predictive significance of MPV in CRC. The retrospective study recruited 509 consecutive CRC patients between January 2009 and December 2009. The relationships between MPV and clinicopathological characteristics were analyzed. Kaplan-Meier method and Cox regression were used to evaluate the prognostic impact of MPV. Of the 509 CRC patients, high MPV levels were detected in 150 (29.5%) patients. Elevated MPV was associated with tumor differentiation (p < 0.001). Patients with increased MPV had poor overall survival compared with those with normal level (60.0% vs. 83.6%, log-rank test, p = 0.035). Cox regression analysis showed that MPV was an independent prognostic factor in CRC (HR = 1.452, 95% CI = 1.118-1.884, p = 0.005). In conclusion, MPV is easily available in routine blood test. Elevated MPV might act as a marker of prognosis and therapeutic target for CRC.

Lower mean platelet volume predicts poor prognosis in renal cell carcinoma.

Altered mean platelet volume (MPV) is found in several malignancies. Remarkably, there is little consensus on using the value of MPV in the prognostic evaluations of renal cell carcinoma (RCC). The aim of this study is to examine the feasibility of MPV value as a prognostic indicator of RCC. The retrospective study recruited 306 consecutive RCC patients between January 2009 and December 2009. The relationships between MPV and clinicopathological characteristics were analyzed. Kaplan-Meier method and Cox regression were used to evaluate the prognostic impact of MPV. Of the 306 RCC patients, low MPV levels were detected in 61 (19.9%) patients. Reduced MPV was associated with histology types, T classification, UCLA Integrated Scoring System (UISS) category, and Mayo clinic stage, size, grade, and necrosis score (SSIGN) category (P < 0.05). Patients with decreased MPV had significantly shorter survival time than patients with normal MPV (P < 0.001). Cox regression analysis revealed that reduced MPV was an independent prognostic factor for overall survival (hazard ratio, 1.758; 95% confidence interval [CI], 1.083-2.855, P = 0.023). Moreover, the prognostic accuracy of TNM stage, UISS, and SSIGN prognostic models were improved when MPV was added. In conclusion, reduced MPV is identified as an independent predictor of adverse clinical outcome in RCC.

Decreased Mean Platelet Volume is Associated with Cervical Cancer Development

Background: Cervical cancer is the most common gynecological malignant disorder worldwide. Activated platelets play a key role in cancer development and progression. Mean platelet volume (MPV) is an early indicator of platelet activation. The aim of the present study was to evaluate MPV levels in patients with cervical cancer. Materials and methods: A total of 181 patients with cervical cancer and 181 controls between January 2015 and June 2015 were included in the study. Patient characteristics and hematologic test data at initial diagnosis were collected and odds ratios (ORs) and 95% confidence intervals (CIs) for risk of cervical cancer were calculated using multivariate logistic regression analyses across MPV quartiles. Results: MPV levels were decreased in patients with cervical cancer compared with control subjects. A significant correlation between MPV and FIGO stage was found. Moreover, after adjusting for other risk factors, the ORs (95%CIs) for cervical cancer according to MPV quartiles were 4.450 (1.975-10.026), 2.505 (1.206-5.202), 0.573 (0.261-1.259), and 1.000, respectively. Conclusions: MPV was found to be independently associated with the presence of cervical cancer. Our results suggest that MPV could be potential diagnostic screening tool.

Platelet Distribution Width and Serum Albumin Levels for Discrimination of Thyroid Cancer From Benign Thyroid Nodules

Thyroid cancer is the most rapidly increasing cancer type among women and the second among men. Early detection greatly improves the prognosis. For this purpose, the platelet distribution width (PDW), an early indicator of platelet activation, might be useful. The aim of this study was to investigate the ability of PDW and serum albumin levels individually or in combination to distinguish between thyroid cancer and benign thyroid nodules. A total of 265 patients with thyroid cancer and 243 with benign thyroid nodules were included in a development set. Then, two groups of 130 cases were enrolled in a validation set. Patient characteristics and hematologic test data at initial diagnosis were collected. Receiver operating characteristic curves (ROC), area under the curve (AUC) values, sensitivity and specificity were estimated. Albumin levels are significantly lower and PDW significantly higher in patients with thyroid cancer compared to the benign cases. Moreover, PDW values prominently differed among three types of thyroid cancer. In addition, the combination of PDW and albumin exhibited a significantly larger AUC than either marker alone (p < 0.001). In conclusion, the combined use of PDW and albumin might be useful in distinguishing thyroid cancer from benign thyroid nodules. This promising approach could be helpful in early detection of thyroid cancer.

Association of decreased mean platelet volume with renal cell carcinoma.

BACKGROUND: Renal cell carcinoma (RCC) is the third most common genitourinary cancer. Activated platelets play a pivotal role in cancer development and progression. Altered mean platelet volume (MPV) has been reported in several malignancies. The aim of the present study was to investigate the association of MPV with RCC. STUDY DESIGN: The study consisted of 145 patients with RCC, 110 patients with benign renal tumor and 132 healthy control subjects between January 2015 and December 2015. All participants' clinical and laboratory characteristics at initial diagnosis were collected. The odds ratios (ORs) for RCC were calculated using multivariate logistic regression analysis after adjusting for confounding variables across MPV quartiles. RESULTS: The patients with RCC had decreased pre-operative MPV compared to the patients with benign renal tumor and healthy control subjects. Furthermore, pre-operative MPV was reduced in benign renal tumor compared with healthy control subjects. Surgical tumor resection resulted in a significant increase in MPV levels (8.7 fL vs. 9.0 fL; p = 0.011). After adjusting for other risk factors, the ORs (95% CIs) for RCC in each MPV quartile were 25.725 (7.556-87.585), 7.447 (2.701-20.537), 0.703 (0.245-2.019), and 1.000, respectively. CONCLUSIONS: RCC patients have remarkably reduced MPV compared to patients with benign renal tumor and healthy control subjects. Moreover, decreased MPV was independently associated with RCC. Our results suggest that detection of MPV may be useful to assess the risk of RCC.

Higher platelet distribution width predicts poor prognosis in laryngeal cancer.

BACKGROUND: Activated platelets promote cancer progression and metastasis. However, the prognostic value of platelet indices in laryngeal cancer remains poorly understood. The purpose of this study was to investigate the predictive significance of platelet indices in laryngeal cancer. RESULTS: Of the 241 patients, high platelet distribution width (PDW) levels were observed in 116 (48.1 %) patients. In the Kaplan-Meier analysis, increased PDW was significantly associated with a poorer overall survival (p < 0.001). In the multivariate Cox model, PDW was an independent prognostic index for overall survival (HR=4.381, 95% CI=2.313-8.298, P < 0.001). METHOD: The retrospective study included 241 consecutive patients with laryngeal cancer between January 2009 and December 2009. The relationships between PDW and clinicopathological characteristics were analyzed. Kaplan-Meier method and Cox regression were used to evaluate the prognostic impact of PDW. CONCLUSIONS: Elevated PDW might be a novel prognostic marker in laryngeal cancer.