Badanie zależności między metylacją regionu promotora genu MMP-9 a nefropatią cukrzycową

Objective: This study aims to explore the relationship between the methylation of matrix metalloproteinase (MMP)-9 gene promoter region and diabetic nephropathy (DN) through the detection of the methylation level of MMP-9 gene promoter region in the peripheral blood of patients with DN in different periods and serum MMP-9 concentration. Methods: The methylation level of the MMP-9 gene promoter region was detected by methylation-specific polymerase chain reaction (MSP), and the content of MMP-9 in serum was determined by enzyme-linked immunosorbent assay (ELISA). Results: Results of the statistical analysis revealed that serum MMP-9 protein expression levels gradually increased in patients in the simple diabetic group, early diabetic nephropathy group and clinical diabetic nephropathy group, compared with the control group; and the difference was statistically significant (P < 0.05). Compared with the control group, the methylation levels of MMP-9 gene promoter regions gradually decreased in patients in the simple diabetic group, early diabetic nephropathy group, and clinical diabetic nephropathy group; and the difference was statistically significant (P < 0.05). Furthermore, correlation analysis results indicated that the demethylation levels of the MMP-9 gene promoter region was positively correlated with serum protein levels, urinary albumin to creatinine ratio (UACR), urea and creatinine; and was negatively correlated with GFR. Conclusion: The demethylation of the MMP-9 gene promoter region may be involved in the occurrence and development of diabetic nephropathy by regulating the expression of MMP-9 protein in serum.Wstęp: Celem pracy jest zbadanie zależności między metylacją regionu promotora genu metaloproteinazy macierzy zewnątrzkomórkowej typu 9 a nefropatią cukrzycową, poprzez wykrycie poziomu metylacji regionu promotora genu MMP-9 we krwi obwodowej pacjentów z nefropatią cukrzycową w różnych okresach i przy różnym stężeniu MMP-9 w surowicy krwi. Materiał i metody: Poziom metylacji regionu promotora genu MMP-9 wykrywano za pomocą metylospecyficznej reakcji łańcuchowej polimerazy (methylation-specific polymerase chain reaction; MSP), natomiast zawartość MMP-9 w surowicy krwi była określana przy użyciu enzymatycznego testu immunoadsorpcyjnego (ELISA). Wyniki: Wyniki analizy statystycznej wykazały, że poziom ekspresji białka MMP-9 w surowicy krwi stopniowo wzrastał w grupie pa­cjentów ze zwykłą cukrzycą, w grupie pacjentów z wczesną nefropatią cukrzycową oraz w grupie z kliniczną nefropatią cukrzycową w porównaniu z grupą kontrolną; różnica była statystycznie istotna (p &lt; 0,05). W porównaniu z grupą kontrolną poziom metylacji regionów promotora genu MMP-9 stopniowo się zmniejszał w grupie pacjentów ze zwykłą cukrzycą, w grupie pacjentów z wczesną nefropatią cukrzycową oraz w grupie z kliniczną nefropatią cukrzycową; różnica była istotna statystycznie (p &lt; 0,05). Ponadto, wyniki analizy korelacji wykazały, że poziomy demetylacji regionu promotora genu MMP-9 były dodatnio skorelowane ze stężeniem białek w surowicy krwi, ze wskaźnikiem albumina/kreatynina (urinary albumin to creatinine ratio; UACR), mocznikiem i kreatyniną oraz były ujemnie skorelowane ze wskaźnikiem GFR. Wnioski: Demetylacja regionu promotora genu MMP-9 może być zaangażowana w występowanie i rozwój nefropatii cukrzycowej poprzez regulację ekspresji białka MMP-9 w surowicy krwi.

Linezolid and Rifampicin Combination to Combat cfr-Positive Multidrug-Resistant MRSA in Murine Models of Bacteremia and Skin and Skin Structure Infection.

Linezolid resistance mediated by the cfr gene in MRSA represents a global concern. We investigated relevant phenotype differences between cfr-positive and -negative MRSA that contribute to pathogenesis, and the efficacy of linezolid-based combination therapies in murine models of bacteremia and skin and skin structure infection (SSSI). As a group, cfr-positive MRSA exhibited significantly reduced susceptibilities to the host defense peptides tPMPs, human neutrophil peptide-1 (hNP-1), and cathelicidin LL-37 (P &lt; 0.01). In addition, increased binding to fibronectin (FN) and endothelial cells paralleled robust biofilm formation in cfr-positive vs. -negative MRSA. In vitro phenotypes of cfr-positive MRSA translated into poor outcomes of linezolid monotherapy in vivo in murine bacteremia and SSSI models. Importantly, rifampicin showed synergistic activity as a combinatorial partner with linezolid, and the EC50 of linezolid decreased 6-fold in the presence of rifampicin. Furthermore, this combination therapy displayed efficacy against cfr-positive MRSA at clinically relevant doses. Altogether, these data suggest that the use of linezolid in combination with rifampicin poses a viable therapeutic alternative for bacteremia and SSSI caused by cfr-positive multidrug resistant MRSA

Device Activity Detection in mMTC with Low-Resolution ADC: A New Protocol

This paper investigates the effect of low-resolution analog-to-digital converters (ADCs) on device activity detection in massive machine-type communications (mMTC). The low-resolution ADCs induce two challenges on the device activity detection compared with the traditional setup with assumption of infinite ADC resolution. First, the codebook design for signal quantization by the low-resolution ADCs is particularly important since a good codebook design can lead to small quantization error on the received signal, which in turn has significant influence on the activity detector performance. To this end, prior information about the received signal power is needed, which depends on the number of active devices $K$. This is sharply different from the activity detection problem in traditional setups, in which the knowledge of $K$ is not required by the BS as a prerequisite. Second, the covariance-based approach achieves good activity detection performance in traditional setups while it is not clear if it can still achieve good performance in this paper. To solve the above challenges, we propose a communication protocol that consists of an estimator for $K$ and a detector for active device identities: 1) For the estimator, the technical difficulty is that the design of the ADC quantizer and the estimation of $K$ are closely intertwined and doing one needs the information/execution from the other. We propose a progressive estimator which iteratively performs the estimation of $K$ and the design of the ADC quantizer; 2) For the activity detector, we propose a custom-designed stochastic gradient descent algorithm to estimate the active device identities. Numerical results demonstrate the effectiveness of the communication protocol.Comment: Submitted to IEEE for possible publicatio