Lipidomic markers for the prediction of progression from mild cognitive impairment to Alzheimer's disease.

Dementia is a well-known syndrome and Alzheimer's disease (AD) is the main cause of dementia. Lipids play a key role in the pathogenesis of AD, however, the prediction value of serum lipidomics on AD remains unclear. This study aims to construct a lipid score system to predict the risk of progression from mild cognitive impairment (MCI) to AD. First, we used the least absolute shrinkage and selection operator (LASSO) Cox regression model to select the lipids that can signify the progression from MCI to AD based on 310 older adults with MCI. Then we constructed a lipid score based on 14 single lipids using Cox regression and estimated the association between the lipid score and progression from MCI to AD. The prevalence of AD in the low-, intermediate- and high-score groups was 42.3%, 59.8%, and 79.8%, respectively. The participants in the intermediate- and high-score group had a 1.65-fold (95% CI 1.10 to 2.47) and 3.55-fold (95% CI 2.40 to 5.26) higher risk of AD, respectively, as compared to those with low lipid scores. The lipid score showed moderate prediction efficacy (c-statistics > 0.72). These results suggested that the score system based on serum lipidomics is useful for the prediction of progression from MCI to AD.

Intraspecific cooperation allows the survival of Staphylococcus aureus staff: a novel strategy for disease relapse.

BACKGROUND: The contribution of interspecies interactions between coinfecting pathogens to chronic refractory infection by affecting pathogenicity is well established. However, little is known about the impact of intraspecific interactions on infection relapse, despite the cross-talk of different strains within one species is more common in clinical infection. We reported a case of chronic refractory pulmonary infection relapse, caused by two methicillin-sensitive S. aureus (MSSA) strains (SA01 and SA02) and revealed a novel strategy for relapse via intraspecific cooperation. METHODS: The hemolytic ability, growth curve, biofilm formation, virulence genes and response of G. mellonella larvae to S. aureus infection were analysed to confirm this hypothesis. RESULTS: SA02 hemolytic activity was inhibited by SA01, along with the expression of hemolysin genes and the virulence factor Hla. Additionally, SA01 significantly enhanced the biofilm formation of SA02. AIP-RNAIII may be a possible pathway for this interaction. Compared with mono-infection, a worse outcome (decreased larval survival and increased microbial burden) of the two MSSA strains coinfected with G. mellonella confirmed that intraspecific interactions indeed enhanced bacterial survival in vivo. CONCLUSION: The intraspecific interaction of S. aureus could lead to chronic refractory infection via pathogenicity changes.

Toll-like receptor 10 expression in B cells is negatively correlated with the progression of primary Sjögren's disease.

Primary Sjögren's Disease (pSjD) is considered a B cell-mediated disease. Toll-like receptor 10 (TLR10) is highly expressed in human B cells, indicating that TLR10 probably plays a vital role in pSjD. We examined TLR10 expression in peripheral B subsets of pSjD patients and analyzed their association with disease activity. We observed that TLR10 expression in total, naïve, memory, and switched memory B cells was significantly increased in low-activity pSjD patients as compared with healthy controls and high-activity patients. TLR10 expression in the above mentioned B subsets (except naïve B) was negatively correlated with serum levels of anti-SSA antibody and BAFF, respectively. Moreover, a higher proportion of high-activity pSjD patients was observed in TLR10 low- than high-expressed patients. Our study concluded that TLR10 expression in CD19+ B and memory B was negatively correlated with pSjD disease activity, suggesting that TLR10 might take part in the progression of pSjD.

Fluorescent on-site detection of multiple pathogens using smartphone-based portable device with paper-based isothermal amplification chip.

The development of cost-effective, portable, and ease-of-use sensing system for on-site genetic diagnostics is highly desirable for pathogen screening and infectious disease diagnosis. This study develops (1) a paper-based biochip which is able to integrate the loop-mediated isothermal amplification (LAMP) protocols for simultaneous detection of Escherichia coli O157:H7, Salmonella spp., and Staphylococcus aureus, and (2) a stand-alone smartphone-based portable device which can control exactly 65 °C for isothermal amplification as well as collect and analyze the thus generated fluorescence signals. The reported sensing system has been successfully demonstrated for foodborne pathogen detection with a limit of detection of 2.8 × 10-5 ng µL-1. Spiked milk samples with concentration as low as 10 CFU mL-1 were successfully determined within 4 h, demonstrating the practicality of the reported sensing system in the fields. The reported sensing system featuring simplicity and reliability is ideally suited for genetic diagnostics in low resource settings.

Adipose triglyceride lipase promotes the proliferation of colorectal cancer cells via enhancing the lipolytic pathway.

Abnormal lipid metabolism is the sign of tumour cells. Previous researches have revealed that the lipolytic pathway may contribute to the progression of colorectal cancer (CRC). However, adipose triglyceride lipase (ATGL) role in CRC cells remains unclear. Here, we find that elevated ATGL positively correlates with CRC clinical stages and negatively associates with overall survival. Overexpression of ATGL significantly promotes CRC cell proliferation, while knockdown of ATGL inhibits the proliferation and promotes the apoptosis of CRC cells in vitro. Moreover, in vivo experiments, ATGL promotes the growth of CRC cells. Mechanistically, ATGL enhances the carcinogenic function of CRC cells via promoting sphingolipid metabolism and CoA biosynthesis pathway-related gene levels by degrading triglycerides, which provides adequate nutrition for the progression of CRC. Our researches clarify for the first time that ATGL is a novel oncogene in CRC and may provide an important prognostic factor and therapeutic target for CRC.

[Differentially expressed long non-coding RNAs in spermatozoa with different fertilizing abilities].

OBJECTIVE: To search for conception capacity-related long non-coding RNAs (lncRNA) and explore their possible roles in fertilization. METHODS: We obtained 10 semen samples, 5 of high and the other 5 of low fertilizing ability, extracted large RNAs, established a cDNA library, and performed RNA sequencing with the HiSeq 2000 sequencing system. Using the bioinformatics method, we assembled and predicted lncRNAs, screened differentially expressed genes between the two groups by NOIseq, analyzed the lncRNAs with the box plot and volcano plot, and determined their expression patterns by hierarchical cluster analysis. We examined the functional classification of differentially expressed lncRNAs by pathway and gene ontology (GO) enrichment and predicted those of some lncRNAs by lncRNA-mRNA interaction analysis and intersection analysis with up- and down-stream cis-acting elements. RESULTS: A total of 147 1615 lncRNAs were identified in all the semen samples, including 463 596 novel ones and 8 019 known ones, with 4 052 differentially expressed lncRNAs, 985 upregulated and the other 3 067 downregulated. Box plot and volcano plot filtering analyses showed statistically significant differences in the expressions of the lncRNAs between the two groups, and so did hierarchical cluster analysis. GO functional annotations manifested the involvement of the differentially expressed lncRNAs in the metabolic process, biological regulation, membrane and organelle formation, and protein-nucleotide binding. Pathway analysis showed that the differentially expressed lncRNAs were related to transport and catabolism, cell motility, signaling molecular interactions, signaling transduction, and signaling pathways in the development and immune systems. The functions of the 5 lncRNAs predicted were shown to be associated with sperm motility, acrosomal reaction and signal transduction during fertilization. CONCLUSIONS: Differentially expressed lncRNAs may play an important role in fertilization and become biomarkers for the assessment of sperm quality.

Reduction of SIRT1 epigenetically upregulates NALP1 expression and contributes to neuropathic pain induced by chemotherapeutic drug bortezomib.

BACKGROUND: Bortezomib is a frequently used chemotherapeutic drug for the treatment of multiple myeloma and other nonsolid malignancies. Accumulating evidence has demonstrated that bortezomib-induced persistent pain serves as the most frequent reason for treatment discontinuation. METHODS: The von Frey test was performed to evaluate neuropathic pain behavior, and real-time quantitative reverse transcription polymerase chain reaction, chromatin immunoprecipitation, western blot, immunohistochemistry, and small interfering RNA were performed to explore the molecular mechanisms in adult male Sprague-Dawley rats. RESULTS: We found that application of bortezomib significantly increased the expression of NALP1 protein and mRNA levels in spinal dorsal horn neurons, and intrathecal application of NALP1 siRNA attenuated the bortezomib-induced mechanical allodynia. In addition, bortezomib also decreased the SIRT1 expression, and treatment with SIRT1 activator resveratrol ameliorated the NALP1 upregulation and mechanical allodynia induced by bortezomib. Meanwhile, knockdown of SIRT1 using the SIRT1 siRNA induced the NALP1 upregulation in dorsal horn and mechanical allodynia in normal animal. These results suggested that reduction of SIRT1 induced the NALP1 upregulation in dorsal horn neurons, and participated in bortezomib-induced mechanical allodynia. Importantly, we found that the binding of SIRT1 and NALP1 promoter region did not change before and after bortezomib treatment, but SIRT1 downregulation increased p-STAT3 expression. Furthermore, the activation of STAT3 enhanced the recruitment of p-STAT3 to the Nalp1 gene promoter, which increased the acetylation of histone H3 and H4 in NALP1 promoter regions and epigenetically upregulated NALP1 expression in the rodents with bortezomib treatment. CONCLUSION: These findings suggested a new epigenetic mechanism for NALP1 upregulation involving SIRT1 reduction and subsequent STAT3-mediated histone hyperacetylation in NALP1 promoter region in dorsal horn neurons, which contributed to the bortezomib-induced mechanical allodynia.

Molecular epidemiology and virulence characteristics of Staphylococcus aureus nasal colonization in medical laboratory staff: comparison between microbiological and non-microbiological laboratories.

BACKGROUND: Medical laboratory staff are a high-risk population for colonization of Staphylococcus aureus (S. aureus) due to direct and dense contact with the pathogens; however, there is limited information about this colonization. This study sought to determine the prevalence and molecular characteristics of nasal colonization by S. aureus in medical laboratory staff in Guangzhou, southern China, and to compare the differences between microbiological laboratory (MLS) and non-microbiological laboratory (NMLS) staff. METHODS: S. aureus colonization was assessed by nasal swab cultures from 434 subjects, including 130 MLSs and 304 NMLSs from 33 hospitals in Guangzhou. All S. aureus isolates underwent the antimicrobial susceptibility test, virulence gene detection and molecular typing. RESULTS: The overall prevalence of S. aureus carriage was 20.1% (87/434), which was higher in MLSs than in NMLSs (26.2% vs. 17.4%, P < 0.05), while the prevalence of Methicillin-resistant S. aureus (MRSA) was similar. Living with hospital staff was associated with S. aureus carriage. The majority of the isolates harboured various virulence genes, and those in MLSs appeared less resistant to antibiotics and more virulent than their counterparts. A total of 37 different spa types were detected; among these, t338, t437, t189 and t701 were the most frequently encountered types. T338 was the main spa type contributing to nasal colonization Methicillin-sensitive S. aureus (MSSA) (13.0%), and t437-SCCmec IV was predominant in MRSA isolates (40%). CONCLUSIONS: These findings provide insight into the risk factors, molecular epidemiology and virulence gene profiles of S. aureus nasal carriage among the medical laboratory staff in Guangzhou.

Dual-aptamer-based voltammetric biosensor for the Mycobacterium tuberculosis antigen MPT64 by using a gold electrode modified with a peroxidase loaded composite consisting of gold nanoparticles and a Zr(IV)/terephthalate metal-organic framework.

An ultrasensitive aptasensor is described for the voltammetric determination of the Mycobacterium tuberculosis antigen MPT64 in human serum. Firstly, an amino-modified Zr(IV) based metal-organic framework (MOF; type UiO-66-NH2; made up from Zr6O32 units and 2-amino-terephthalate linkers) with a high specific surface was synthesized and used as the carrier of the gold nanoparticles and the aptamers. Then the signalling nanoprobe was fabricated after the horseradish peroxidase was cast on the nanomaterials. The two aptamers with synergistic effect on binding MPT64 were anchored on the gold electrode. Differential pulse voltammetry indicated that the peak current is highest if the ratio of the two aptamers is 1:1. The assay has a wide linear response range (0.02 to 1000 pg·mL-1 of MPT64) and a 10 fg·mL-1 detection limit at a working potential of around -96 mV (vs Ag/AgCl). The results show this biosensor to be a viable tool for detection of tuberculosis at an early stage. Graphical abstract Schematic presentation of the construction of the nanoprobe and biosensor. Firstly, the surface of UiO-66-NH2 was anchored to gold nanoparticles (AuNPs). A dual-aptamer and HRP were added to form the signalling nanoprobe (Aptamer/HRP/AuNPs/UiO-66-NH2). Then, the aptamers I and II were attached on the surface of gold electrode and 6-mercapto-1-hexanol was used to block the uncovered active site of the gold electrode. Finally, after incubation with MPT64, the signalling nanoprobe was dropped on the modified electrode and the DPV measurements was used for the analysis of Mycobacterium tuberculosis antigen MPT64. (PVP: poly(vinyl pyrrolidone); HRP: horseradish peroxidase; MCH: 6-Mercapto-1-hexanol; HQ: hydroquinone; BQ: benzoquinone).

Effect of NR5A2 inhibition on pancreatic cancer stem cell (CSC) properties and epithelial-mesenchymal transition (EMT) markers.

NR5A2 (aka LRH-1) has been identified as a pancreatic cancer susceptibility gene with missing biological link. This study aims to demonstrate expression and potential role of NR5A2 in pancreatic cancer. NR5A2 expression was quantified in resected pancreatic ductal adenocarcinomas and the normal adjacent tissues of 134 patients by immunohistochemistry. The intensity and extent of NR5A2 staining was quantified and analyzed in association with overall survival (OS). The impact of NR5A2 knockdown on pancreatic cancer stem cell (CSC) properties and epithelial-mesenchymal transition (EMT) markers was examined in cancer cells using RT-PCR and Western Blot. NR5A2 was overexpressed in pancreatic tumors, the IHC-staining H score (mean ± SE) was 96.4 ± 8.3 in normal versus 137.9 ± 8.2 in tumor tissues (P < 0.0001). Patients with a higher NR5A2 expression had a median survival time 18.4 months compared to 23.7 months for those with low IHC H scores (P = 0.019). The hazard ratio of death (95% confidence interval) was 1.60 (1.07-2.41) after adjusting for disease stage and tumor grade (P = 0.023). NR5A2 was highly expressed in pancreatic cancer sphere forming cells. NR5A2-inhibition by siRNA was associated with reduced sphere formation and decreased levels of CSCs markers NANOG, OCT4, LIN28B, and NOTCH1. NR5A2 knockdown also resulted in reduced expression of FGB, MMP2, MMP3, MMMP9, SNAIL, and TWIST, increased expression of epithelial markers E-cadherin and ß-catenin, and a lower expression of mesenchymal marker Vimentin. Taken together, our findings suggest that NR5A2 could play a role in CSC stemness and EMT in pancreatic cancer, which may contribute to the worse clinical outcome.

[A novel double heterozygote of HBB c.[219T>A;220G>T]: gene diagnosis and pedigree analysis].

OBJECTIVE: To identify a novel hemoglobinopathy applied by direct sequencing and clone sequencing. METHODS: EDTA anticoagulated blood of proband and his parents were analyzed by hematology analyzers and Capillarys hemoglobin electrophoresis (CE). Then thalassemia genetypes were screened by gap-PCR and reverse dot blot (RDB). Proband was suspected with abnormal hemoglobin combine alpha beta compound thalassemia. The mutation of beta-globin was identified by direct sequencing and clone sequencing. RESULTS: Hb analysis showed that probands Hb A2 variant was eluted in Z (C) zone and his father's in Z (A2) zone on CE,and proband's mother elevated HbA2 of 4.6%. Screened by RDB, the proband was CD71-72(+A) homozygote and showed the mismatch with his parents. Through direct sequencing and clone sequencing, we deduced that our proband inherited the mutations of HBB c.[219T>A;220G>T] from his father and inherited the Southeast-Asian deletion and HBB c.216-217insA from his mother. CONCLUSION: A novel double heterozygote of HBB c.[219T>A; 220G>T] was identified in south China. This mutation enriches the beta-thalassemia gene mutation spectrum in Chinese population.

Declined Natural Killer Cells Emerging in Women with Unexplained Recurrent Spontaneous Abortion and Further Reducing after Medical Therapy.

BACKGROUND: As focus grows on reproduction, the issue of Recurrent Spontaneous Abortion (RSA), especially for unexplained reasons (URSA), is grabbing more and more attention in gynecological immunology. We investigated the changes of peripheral lymphocyte subsets focusing on whether they had some relationship with development of URSA. METHODS: The percentage and absolute count of lymphocyte subsets (T cells, Th cells, Ts cells, B cells, NK cells) were simultaneously evaluated by flow cytometry in URSA patients (n = 48) and healthy controls (HC, n = 22). RESULTS: Significantly lower percentage and absolute counts of NKT cells and NK cells were observed in URSA compared to the HC. After medical therapy, an obviously increase was shown in the percentage of both T cells and B cells, whereas it presented a reduction in the percentage of NK cells. CONCLUSIONS: The flow cytometry test in T, B, NK cells is a method available to identify URSA patients from healthy women and to provide reference guides for clinical therapy.

A multiplex blood-based assay targeting DNA methylation in PBMCs enables early detection of breast cancer.

The immune system can monitor tumor development, and DNA methylation is involved in the body's immune response to tumors. In this work, we investigate whether DNA methylation alterations in peripheral blood mononuclear cells (PBMCs) could be used as markers for early detection of breast cancer (BC) from the perspective of tumor immune alterations. We identify four BC-specific methylation markers by combining Infinium 850 K BeadChips, pyrosequencing and targeted bisulfite sequencing. Based on the four methylation markers in PBMCs of BC, we develop an efficient and convenient multiplex methylation-specific quantitative PCR assay for the detection of BC and validate its diagnostic performance in a multicenter cohort. This assay was able to distinguish early-stage BC patients from normal controls, with an AUC of 0.940, sensitivity of 93.2%, and specificity of 90.4%. More importantly, this assay outperformed existing clinical diagnostic methods, especially in the detection of early-stage and minimal tumors.

DNA Methylation-Based Testing in Peripheral Blood Mononuclear Cells Enables Accurate and Early Detection of Colorectal Cancer.

An effective blood-based method for the diagnosis of colorectal cancer has not yet been developed. Molecular alterations of immune cells occur early in tumorigenesis, providing the theoretical underpinning for early cancer diagnosis based on immune cell profiling. Therefore, we aimed to develop an effective detection method based on peripheral blood mononuclear cells (PBMC) to improve the diagnosis of colorectal cancer. Analysis of the genome-wide methylation landscape of PBMCs from patients with colorectal cancer and healthy controls by microarray, pyrosequencing, and targeted bisulfite sequencing revealed five DNA methylation markers for colorectal cancer diagnosis, especially early-stage colorectal cancer. A single-tube multiple methylation-specific quantitative PCR assay (multi-msqPCR) for simultaneous detection of five methylation markers was established, which allowed quantitative analysis of samples with as little as 0.1% PBMC DNA and had better discriminative performance than single-molecule detection. Then, a colorectal cancer diagnostic model (CDM) based on methylation markers and the multi-msqPCR method was constructed that achieved high accuracy for early-stage colorectal cancer (AUC = 0.91; sensitivity = 81.18%; specificity = 89.39%), which was improved compared with CEA (AUC = 0.79). The CDM also enabled a high degree of discrimination for advanced adenoma cases (AUC = 0.85; sensitivity = 63.04%). Follow-up data also demonstrated that the CDM could identify colorectal cancer potential up to 2 years before currently used diagnostic methods. In conclusion, the approach constructed in this study based on PBMC-derived DNA methylation markers and a multi-msqPCR method is a promising and easily implementable diagnostic method for early-stage colorectal cancer. SIGNIFICANCE: Development of a diagnostic model for early colorectal cancer based on epigenetic analysis of PBMCs supports the utility of altered DNA methylation in immune cells for cancer diagnosis.

Pseudohyperchloremia caused by the long-term use of phenobarbital and sodium bromide compound tablets: a case report.

Background: Serum chloride (Cl-), which is an important analyte that reflects the electrolyte and acid-base balance in humans, is affected by several specific agents or substances. It has been reported that the abuse of bromine-containing drugs, such as bromvalerylurea may lead to pseudohyperchloremia, which is very rare yet, caused by the treatment dose of bromine-containing drugs. In this case report, we describe an epilepsy patient whose serum Cl- was falsely elevated due to the long-term use of phenobarbital and sodium bromide compound tablets. We also discuss the anti-interference capacity of different analyzers and the disturbance of bromide-containing drugs in Cl- determination. Case Description: A 34-year-old woman diagnosed with epilepsy for 11 years was admitted to our hospital for further treatment. She had increasingly frequent loss of consciousness and seizures. Her medication history included carbamazepine, levetiracetam, phenobarbital and sodium bromide compound tablets. The video electroencephalogram (VEEG) was moderately abnormal. No obvious abnormality was found in blood routine test, liver and kidney function, except an aberrantly elevated serum Cl- level of 130 mmol/L; however, the patient did not present with the relevant signs and symptoms of hyperchloremia, such as thirst, fatigue, nausea and vomiting. Subsequently, we used three different analyzers to determine her Cl- level and obtained the following results: an arterial blood Cl- level of 107 mmol/L; a serum Cl- level of 112 mmol/L; and no result. Reviewing her medical history, we discovered that the patient had been taking phenobarbital and sodium bromide compound tablets for 6 months to treat her seizures. Her serum bromide was 4.89 mmol/L, which may cause pseudohyperchloremia. After changing her treatment to phenobarbital tablets, her serum Cl- returned to the normal range (106 mmol/L). Conclusions: Bromide-containing drugs can cause a falsely elevated Cl- level. When pseudohyperchloremia is suspected, different methods or instruments should be used to measure Cl- levels.

Virus Detection: From State-of-the-Art Laboratories to Smartphone-Based Point-of-Care Testing.

Infectious virus outbreaks pose a significant challenge to public healthcare systems. Early and accurate virus diagnosis is critical to prevent the spread of the virus, especially when no specific vaccine or effective medicine is available. In clinics, the most commonly used viral detection methods are molecular techniques that involve the measurement of nucleic acids or proteins biomarkers. However, most clinic-based methods require complex infrastructure and expensive equipment, which are not suitable for low-resource settings. Over the past years, smartphone-based point-of-care testing (POCT) has rapidly emerged as a potential alternative to laboratory-based clinical diagnosis. This review summarizes the latest development of virus detection. First, laboratory-based and POCT-based viral diagnostic techniques are compared, both of which rely on immunosensing and nucleic acid detection. Then, various smartphone-based POCT diagnostic techniques, including optical biosensors, electrochemical biosensors, and other types of biosensors are discussed. Moreover, this review covers the development of smartphone-based POCT diagnostics for various viruses including COVID-19, Ebola, influenza, Zika, HIV, et al. Finally, the prospects and challenges of smartphone-based POCT diagnostics are discussed. It is believed that this review will aid researchers better understand the current challenges and prospects for achieving the ultimate goal of containing disease-causing viruses worldwide.

[The Clinical Value of Combined Detection of RBC, Ret-He and HbA2 for Thalassemia].

OBJECTIVE: To investigate the distribution of Ret-He and RBC in thalassemia and the value of combining HbA2 in the detection of thalassemia among patients with microcytic or hypochromic. METHODS: 145 patients with microcytic or hypochromic outpatient or hospitalization in our hospital from May 2018 to December 2019 were selected and were divided into the thalassemia group(68 cases) and the non-thalassemia group (77 cases), and at the same time, the patients were divided into four groups of the non-anemia, mild anemia, moderate anemia and severe anemia group according to the degree of anemia. The Ret-He, RBC, RDW-CV and HbA2 in patients were detected, and the distribution of these parameters were compared, and the joint detection of Ret-He, RBC and HbA2 about its sensitivity, specific and other indicators of auxiliary diagnosis of thalassemia were analyzed. RESULTS: Among patients with microcytic or hypochromic, according to the anemia grade Ret-He gradually decreased from the non-anemia group to the severe anemia group (P<0.05); while RDW-CV was increased gradually from the mild anemia group to the severe anemia group (P<0.05); both RBC and Ret-He were increased in the thalassemia group as compared with the non- thalassemia group (P<0.05); while RDW-CV was decreased in the thalassemia group as compared with the non-thalassemia group (P<0.05); meanwhile Ret-He in the α-thalassemia group was higher than that in the ß-thalassemia group. ROC curve analysis showed that combined with HbA2, the specificity was 93.51%, the sensitivity was 66.18%, the positive predictive value was 90% and the negative predictive value was 75.189% when Ret-He was truncated with 19.25 pg and RBC was truncated with 4.95×1012/L. CONCLUSION: Among patients with microcytic or hypochromic, the distribution of RBC, Ret-He and RDW-CV was different in the thalassemia group and the non-thalassemia group, and was also affected by the degree of anemia. Combined Ret-He and RBC could improve the diagnostic specificity for thalassemia, which were screened by HbA2 in patients with microcytic or hypochromic.

Hemoglobin Fukuoka caused unexpected hemoglobin A1c results: A case report.

BACKGROUND: Glycated hemoglobin (Hb) (HbA1c) is an indicator that is used to diagnose and monitor the treatment of diabetes. Many factors can affect the detection of HbA1c. One of the most important of these factors is the Hb variant. Here, we report a rare Hb variant and evaluate its effect on HbA1c. CASE SUMMARY: A 35-year-old man was suspected of harboring an Hb variant following the measurement of HbA1c with the Variant II Turbo 2.0 Hb detection system during a routine examination. Subsequently, we used the Arkray HA-8160 and ARCHITECT c4000 system to reanalyze HbA1c. Finally, the Hb variant was detected with a Capillary2FP analyzer that operates on the principle of capillary electrophoresis. We also used gene sequencing to investigate the mutation site. The value of HbA1c detected with the Variant II Turbo 2.0 system was 52.7%. However, the Arkray HA-8160 system did not display a result while the ARCHITECT c16000 system showed a result of 5.4%. The Capillary2FP analyzer did not reveal any abnormal Hb zones. However, gene sequencing identified the presence of a mutation in the Hb ß2 chain [CD2(CAC>TAC), His>Tyr, HBB: c.7C>T]; the genotype was Hb Fukuoka. CONCLUSION: Hb variants could cause abnormal HbA1c results. For patients with Hb variants, different methods should be used to detect HbA1c.

miR-362-5p promotes cell proliferation and cell cycle progression by targeting GAS7 in acute myeloid leukemia.

Recently, miR-362-5p has attracted special interest as a novel prognostic predictor in acute myeloid leukemia (AML). However, its biological function and underlying molecular mechanism in AML remain to be further defined. Herein, we found that a significant increase in miR-362-5p expression was observed in AML patients and cell lines using quantitative real-time PCR. The expression of miR-362-5p was altered in THP-1 and HL-60 cells by transfecting with miR-362-5p mimic or inhibitor. A series of experiments showed that inhibition of miR-362-5p expression significantly suppressed cell proliferation, induced G0/G1 phase arrest and attenuated tumor growth in vivo. On the contrary, ectopic expression of miR-362-5p resulted in enhanced cell proliferation, cell cycle progression and tumor growth. Moreover, growth arrest-specific 7 (GAS7) was confirmed as a direct target gene of miR-362-5p and was negatively modulated by miR-362-5p. GAS7 overexpression imitated the tumor suppressive effect of silenced miR-362-5p on THP-1 cells. Furthermore, miR-362-5p knockdown or GAS7 overexpression obviously down-regulated the expression levels of PCNA, CDK4 and cyclin D1, but up-regulated p21 expression. Collectively, our findings demonstrate that miR-362-5p exerts oncogenic effects in AML by directly targeting GAS7, which might provide a promising therapeutic target for AML.

Chiauranib selectively inhibits colorectal cancer with KRAS wild-type by modulation of ROS through activating the p53 signaling pathway.

Colorectal cancer (CRC) is one of the top three most deadly cancers despite using chemotherapy based on oxaliplatin or irinotecan combined with targeted therapy. Chiauranib has recently been identified to be a promising anticancer candidate with impressive efficacy and safety. However, the role and molecular mechanisms of Chiauranib in the treatment of CRC remain to be elucidated. Our study shows that Chiauranib inhibits cell proliferation and induces apoptosis in KRAS wild-type CRC cells in a dose- and time-dependent manner, but not mutation ones. Meanwhile, Chiauranib increases ROS production in KRAS wild-type CRC cells. Moreover, Chiauranib selectively suppresses KRAS wild-type CRC cells growth in vivo. Mechanistically, Chiauranib inhibits KRAS wild-type CRC cells by triggering ROS production via activating the p53 signaling pathway. Further, KRAS mutation CRC cells are resistant to Chiauranib by increasing Nrf2 to stably elevate the basal antioxidant program and thereby lower intracellular ROS induced by Chiauranib. Our findings provide the rationale for further clinical evaluation of Chiauranib as a therapeutic agent in treating KRAS wild-type CRC.