An adverse intrauterine environment reflected by low birth weight (LBW) and prematurity may induce fetal programming that favors kidney dysfunction in adulthood. We examined the association of LBW and prematurity with blood pressure (BP) and kidney function markers in non-diabetic, middle-aged adults without kidney disease from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).
A cross-sectional analysis of 768 subjects aged 35-54 years was conducted. Comparisons were performed according to self-reported birth weight: LBW (< 2.5 kg) or normal birth weight (2.5-4.0 kg). Associations of LBW and prematurity with BP levels and kidney function markers \"(estimated glomerular filtration rate [eGFR], albumin-creatinine ratio [ACR] and serum cystatin-C) were tested by multiple linear regression using adjustments based on Directed Acyclic Graphs. Propensity score matching was applied to control imbalances.
Mean age of participants was 45.5 ± 4.6 years and 56.8% were female; 64 (8.3%) participants reported LBW and 39 (5.0%) prematurity. The LBW group had higher systolic (p = 0.015) and diastolic BP (p = 0.014) and ACR values (p = 0.031) and lower eGFR (p = 0.015) than the normal birth weight group, but no group difference for cystatin-C was found. The preterm group had higher mean levels of systolic and diastolic BP, but no difference in kidney function markers was evident. In a regression model adjusted for sex, skin color and family history of hypertension, both systolic and diastolic BP levels were associated with LBW, but this association disappeared after adding for prematurity, which remained associated with BP (p = 0.017). Having applied a propensity score matching, LBW was associated with ACR values (p = 0.003), but not with eGFR or BP levels.
The study findings of independent associations of prematurity with higher BP levels, and of LBW with markers of kidney function in adulthood, support that early life events may predict risk for hypertension and kidney dysfunction in adulthood. The study design precluded the inferring of causality, and prospective studies are needed to further investigate this hypothesis.

We aimed to evaluate the relationship of fatty liver, estimated by the fatty liver index (FLI), with kidney function and chronic kidney disease (CKD) in a German cohort study, given the lack of prospective evidence in Europeans.
We included 2920 participants (51.6% women, mean age 56.1 years) from the KORA study, of which 1991 were followed up for an average of 6.5 years (± 0.3). Kidney function was assessed using the glomerular filtration rate estimated by creatinine (eGFR-Cr) or cystatin C (eGFR-cC). We used multiple logistic or linear regressions to evaluate the associations between the FLI, kidney function and CKD (eGFR < 60 ml/min/1.73 m2) and mediation analysis to explore the mediation effects of metabolic factors.
The prevalence of FLI ≥60 and CKD was 40.4% and 5.6% at baseline, respectively, and 182 participants developed CKD during the follow-up. Cross-sectionally, FLI was significantly inversely associated with eGFR-cC {β = -1.14 [95% confidence interval (CI) -1.81 to -0.47]} and prevalent CKD based on eGFR-cC [OR 1.28 (95% CI 1.01-1.61)], but not with other markers. After adjusting for lifestyle factors, we found a positive association between FLI and incident CKD defined by eGFR-cC or/eGFR-Cr, which was attenuated after controlling for metabolic risk factors. Mediation analysis showed that the association was completely mediated by inflammation, diabetes and hypertension jointly.
The positive association between FLI and CKD incidence was fully mediated by the joint effect of metabolic risk factors. Future longitudinal studies need to explore the chronological interplay between fatty liver, cardiometabolic risk factors and kidney function with repeated measurements.

To investigate the changes of serum cystatin C (Cys-C), beta 2-microglobulin (β2-MG), urinary neutrophil gelatinase-associated lipocalin (NGAL), and alpha 1-microglobulin (α1-MG) in asphyxiated neonates, and to evaluate the value of combined detection of multiple biomarkers in the early diagnosis of acute kidney injury (AKI) in asphyxiated neonates.
A total of 110 full-term asphyxiated and 30 healthy neonates were included. The asphyxia neonates were divided into AKI and non-AKI groups. Serum Cys-C, β2-MG, urine NGAL, and α1-MG were measured 24 h after birth. The diagnostic value of the biomarkers was determined using receiver operating characteristic (ROC) curves.
There was no significant difference in serum creatinine and blood urea nitrogen among the control group, moderate asphyxia group, and severe asphyxia group at 24 h after birth. Significant differences were noticed in terms of serum Cys-C, β2-MG, urinary NGAL, and α1-MG among the 3 groups. Moreover, with the aggravation of asphyxia, the above indicators gradually increased. There were significant differences in the 4 indicators between the AKI and non-AKI groups (p < 0.05). The area under the ROC curve of the above indicators was 0.670, 0.689, 0.865, and 0.617, respectively (p < 0.05). The sensitivity and specificity of the combined diagnosis of asphyxia neonatorum AKI with the 4 indicators were 0.974 and 0.506, respectively.
Serum Cys-C, β2-MG, urine NGAL, and α1-MG are early specific indicators for the diagnosis of renal injury after neonatal asphyxia. Combined detection of these parameters could aid clinical evaluation of renal injury in asphyxiated neonates.

Drug protein interactions have gained considerable attention over the past many years. In the current communication the association of muscle cystatin (MC) with anti-rheumatic drugs methotrexate and dexamethasone was studied by thiol proteinase inhibitor assay, ultra violet (UV) absorption, fluorescence spectroscopy, and fluorescence transform infra-red spectroscopy (FTIR). A static pattern of quenching was noticed between muscle cystatin and methotrexate (MTX). Binding constant (Ka) of methotrexate to muscle cystatin was found to be 1 × 10-7 M-1 and the stoichiometry of binding was calculated to be one. Fluorescence measurement of the emission quenching reveals that the quenching process of cystatin by dexamethasone (DXN) was also static. The stoichiometry of binding and binding constant was also obtained. Additional evidence regarding MTX-MC and DXN-MC was obtained from UV spectroscopy and FTIR spectroscopic results. Such spectroscopic studies would help in modelling new candidate drugs for rheumatoid arthritis based on their cystatin binding profile.Communicated by Ramaswamy H. Sarma.

Oxyfluorfen (2-chloro-1-(3-ethoxy-4-nitrophenoxy)-4-(trifluoromethyl)benzene) is a nitrophenyl ether herbicide. Phytocystatins are crucial plant proteins which regulate various physiological processes and are also responsible for maintaining protease-antiprotease balance within plants. Thus, the present article deciphers the interaction of oxyfluorfen with garlic phytocystatin (GPC) through various spectroscopic and calorimetric techniques. The cysteine proteinase inhibitory assay was done to assess the inhibitory action of GPC in the presence of oxyfluorfen. The GPC loses its inhibitory activity in the presence of oxyfluorfen. The complex formation of GPC-oxyfluorfen was shown by UV absorption spectroscopy. The intrinsic fluorescence experiment affirmed the quenching of GPC in the presence of oxyfluorfen. The Stern-Volmer quenching constant and binding constant was obtained as 6.89 × 103 M-1 and 9.72 × 103 M-1, respectively. Synchronous fluorescence showed the alteration in the microenvironment around tyrosine residues. 3D fluorescence suggested the perturbation in the polarity around aromatic residues. The isothermal titration experiment suggests that the interaction of oxyfluorfen with GPC is a thermodynamically favorable reaction. Secondary structure alteration of GPC in the presence of oxyfluorfen was studied by circular dichroism (CD). The CD result showed a reduction in the α-helical content of GPC on interaction with oxyfluorfen. Consequently, all these outcomes affirmed the formation of GPC-oxyfluorfen complex along with the structural and conformational alteration. This study identifies and signifies that the exposure of oxyfluorfen induces stress within the plant system. Communicated by Ramaswamy H. Sarma.

UNASSIGNED: To evaluate renal function, the indices of estimated glomerular filtration rate (eGFR) obtained using several equations, including the Japanese versions of the serum creatinine-based MDRD equation (eGFRcreat), Chronic Kidney Disease Epidemiology Collaboration equation (eGFR-EPI), and serum cystatin C-based equation (eGFRcys), are utilized. This study prospectively examined the association between these eGFR values and all-cause mortality during a 12-year observational period in a community-based population.
UNASSIGNED: The subjects of this study were 1312 participants undergoing a health checkup, aged ≥40 years. In the total population, the mean eGFR values (mL·min-1·1.73 m-2) were 81.5 for eGFRcreat, 78.1 for eGFR-EPI, and 76.6 for eGFRcys. There were 141 deaths during the observation period, and the area under the receiver operating characteristic curve for predicting mortality was 0.59 for eGFRcreat, 0.67 for eGFR-EPI, and 0.70 for eGFRcys (all P < 0.01). In the Cox proportional analysis adjusted for age and sex, eGFRcys, but not eGFRcreat and eGFR-EPI, showed a significant association with all-cause mortality (per 15 mL·min-1·1.73 m-2 decrease: hazard ratio 1.40, 95% confidence interval 1.18-1.67).
UNASSIGNED: This study revealed that eGFRcys showed lower values than eGFRcreat and eGFR-EPI and was significantly associated with all-cause mortality in the Japanese community-based population.

Cysteine proteinase inhibitors play an essential role in maintaining the proper functioning of all living cells by virtue of its thiol protease regulatory properties. Chemical denaturation of a new variant of cystatin super family has been studied by various biophysical techniques in order to characterize the unfolded and denatured state. Denaturation of garlic phytocystatin (GPC) has been investigated using urea and guanidine hydrochloride (GdnHCl). Different biophysical techniques such as intrinsic fluorescence, circular dichroism and FTIR exhibited an altered structure of garlic phytocystatin with increasing concentration of denaturant. The inhibitory activity of GPC decreases with increasing concentration of denaturant. Increased fluorescence intensity along with red shift reflects the unfolding of GPC at higher concentration of denaturant. GdnHCl induced unfolding showed presence of indiscernible intermediate as followed by ANS binding studies. However, denaturation by urea did not show any intermediates. Mid-point transition was observed at 4.7±0.1M urea and 2.32±0.1M GdnHCl. Circular dichroism and FTIR results indicate the 50% loss of secondary structure at 5M urea and 2.5M GdnHCl. This study provides intriguing insight into the possible alteration of structure, stability and function of GPC induced by urea and GdnHCl.

BACKGROUND: Quantitative changes of salivary proteins due to acute stress were detected.
OBJECTIVE: To explore protein markers of stress in saliva of eight medical residents who performed emergency medicine simulations.
METHODS: Saliva was collected before the simulations, after the simulations, and following morning upon waking. Proteins were separated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), identified by mass spectrometry (MS), and relatively quantified by densitometry.
RESULTS: Salivary alpha-amylase and S-type cystatins significantly increased, while the ∼26 kDa and low-molecular weight (MW) (<10 kDa) SDS-PAGE bands exhibited changes after stress.
CONCLUSIONS: Alpha-amylase and cystatins are potential salivary markers of acute stress, but further validation should be performed using larger sample populations.

To evaluate 47 biomarkers (selected from the current medical literature), in isolation or in combination with placental growth factor (PlGF), to determine the need for delivery within 14 days, in women presenting with suspected preterm preeclampsia.
In a prospective, multicenter observational study, 47 biomarkers were measured in 423 women presenting with suspected preterm preeclampsia (in two prespecified groups: group 1 at less than 35 weeks of gestation and group 2 presenting between 35 0/7 and 36 6/7 weeks of gestation) to evaluate their ability to determine the primary endpoint: preeclampsia requiring delivery within 14 days. Using factor analysis and stepwise logistic regression, we sought one or more additional biomarkers for optimal determination of the primary endpoint.
In women presenting at less than 35 weeks of gestation (n=286), the best performing combination of PlGF, podocalyxin, endoglin, procalcitonin (receiver operating curve [ROC] area 0.90, 95% confidence interval [CI] 0.86-0.93) was not statistically better than PlGF alone (ROC 0.87, 95% CI 0.83-0.92; P=.43) for preeclampsia requiring delivery within 14 days. Two other single markers had test performance that was not significantly different to PlGF (soluble fms-like tyrosine kinase-1 [sFlt-1] ROC 0.83, 95% CI 0.78-0.88; endoglin ROC 0.83, 95% CI 0.79-0.88). Similar findings were found in women presenting between 35 0/7 and 36 6/7 weeks of gestation (n=137): ROC for PlGF alone 0.75 (95% CI 0.67-0.83); ROC for PlGF, cystatin, pregnancy-associated plasma protein A in combination 0.81 (95% CI 0.74-0.88; P=.40).
This study supports the growing body of evidence that a single angiogenesis-related biomarker (PlGF, sFlt-1, or endoglin) alone represents a useful diagnostic test for women presenting with suspected preterm preeclampsia.

The study shows the effect of nonenzymatic glycation on conformation and inhibitory activity of chick pea cystatin (CPC). CPC was incubated with different reducing sugars, pentose (D-Ribose), hexoses (D-Glucose, D-Fructose) at 37 °C for 5 weeks. To evaluate the modification of CPC by these different sugars during the glycation process the extent of the Maillard reaction, conformational, structural and functional changes were investigated. The behaviour of glycated CPC was monitored by the techniques of UV and fluorescence spectroscopies. Specific fluorescence was employed to characterise the glycation and AGEs. The anti-papain activity of glycated CPC was found to be significantly lower as compared to its non-glycated form. Glycation with ribose led to maximum loss in inhibitory activity. It was found that the incubation of CPC with all the mentioned sugars led to a parallel increase in tryptophan fluorescence as well as in Maillard and other AGEs specific fluorescence values and hyperchromicity in the UV-region. Among the sugars studied comparatively ribose was found to be the most active in inducing structural and conformational alterations in the protein suggesting its high reactivity with protein amino groups.