Melatonin derivative 6a as a PARP-1 inhibitor for the treatment of Parkinson's disease.

Both continuous oxidative stress and poly (ADP-ribose) polymerase 1 (PARP-1) activation occur in neurodegenerative diseases such as Parkinson's disease. PARP-1 inhibition can reverse mitochondrial damage and has a neuroprotective effect. In a previous study, we synthesized melatonin derivative 6a (MD6a) and reported that it has excellent antioxidant activity and significantly reduces α-synuclein aggregation in Caenorhabditis elegans; however, the underlying mechanism is largely unknown. In the present study, we revealed that MD6a is a potential PARP-1 inhibitor, leading to mammalian targe of rapamycin/heat shock factor 1 signaling downregulation and reducing heat shock protein 4 and 6 expression, thus helping to maintain protein homeostasis and improve mitochondrial function. Together, these findings suggest that MD6a might be a viable candidate for the prevention and treatment of Parkinson's disease.

Osteoblastic Bone Reaction Developing During Treatment With Sintilimab and Bevacizumab in a Patient With KRASG12V-Mutant Lung Adenocarcinoma.

Osteoblastic bone reaction, the occurrence of new osteoblastic lesions, is a paradoxical phenomenon during the treatment of cancers and can be defined as disease progression or bone metastases. Osteoblastic bone reactions usually occur in patients who receive treatments such as chemotherapy or hormonal or targeted therapy; however, it is difficult to differentiate them from disease progression or an increase in osteoblastic activity in response to therapy. Although osteoblastic bone reaction in lung cancer has been described in a few reports, it has never been reported in patients with KRASG12V-mutant lung adenocarcinoma treated with immunotherapy and antiangiogenesis. Here, we describe a case of a 77-year-old male with KRASG12V-mutant lung adenocarcinoma whose osteoblastic bone response was found during treatment with sintilimab and bevacizumab. We showed the course of the disease as well as systematic imaging manifestations of lung cancer with osteoblastic bone reaction and discussed their mechanisms.

Oxidative NHC catalysis: direct activation of ß sp3 carbons of saturated acid chlorides.

The first activation of saturated acid chlorides by oxidative N-heterocyclic carbene catalysis has been successfully utilized to synthesize enantio-enriched spirooxindole lactones and δ-lactones. The reaction involves the transformation of the ß sp3 carbon of saturated acid chlorides into an electrophilic carbon as a key step. The product was obtained in excellent yield and stereoselectivity.

Optimal Matrix Preparation Methods for Matrix-assisted Laser Desorption/ionisation Time-of-flight Mass Spectrometry Profiling of Low Molecular Weight Peptides in Human Saliva and Serum Samples.

OBJECTIVE: To develop standard experimental methods to minimise technical variance in matrix preparation for MALDI-TOF MS (matrix-assisted laser desorption/ionisation time-offlight) profiling. METHODS: Matrix factors in saliva and serum samples of 20 healthy volunteers were examined, assuring their peptide components using seven different matrix type/preparation methods, HCCA(a-cyano-4-hydroxycinnamic acid)/SM(sample/matrix), SA(sinapinic acid)/DD(dried droplet), SA/SM, DHB(2.5-dihydroxyhenz-zoic acid)/DD, DHB/SM, DHAP(2.5-dihydroxyacetophenone)/ DD, DHAP/SM. Number of peaks, S/N(signal to noise) ratio and approximate range of target peaks were set as main selection criteria to find if these spell out any common regularity in results. RESULTS: Different methods perform differently. DHB/DD performed worst in both samples, with no effective peak detected. For saliva sample, the S/N ratios of other six methods were lower. M/z range distributed differently. DHB/SM and DHAP/DD performed best in number of peaks, m/z distributing in 1000 to 2000 account for the vast majority. For serum sample, S/N ratios and m/z range distribution were different in different methods. S/N ratio of SA/DD and SA/SM were higher, number of peaks and m/z distribution were not irreplaceable. S/N ratios of the other four methods were lower. CONCLUSION: DHAP/DD and HCCA/SM performed best in number of peaks, m/z in 5000 - 7000 account for the vast majority in HCCA/SM and 1000 - 2000 in DHAP/DD. Further studies should focus on other characteristics of peptide components detected in different matrix methods to increase evidence when selecting matrix type/preparation methods.

Analysis of Spino-pelvic Sagittal Alignment in Young Chinese Patients with Lumbar Disc Herniation.

OBJECTIVE: Few studies have concentrated on the sagittal alignment of lumbar disc herniation (LDH), especially the parameters of the pelvis, and controversy exists about whether pelvic morphology is involved in the pathogenesis of LDH. The present study analyzed the characteristics of the sagittal alignment in young Chinese LDH patients and explored the impact of pelvic morphology on the pathogenesis of LDH. METHODS: A retrospective analysis was conducted on 100 young patients with LDH (69 men and 31 women, aged 18-35 years), and the clinical and imaging findings met the criteria for the diagnosis of LDH. The control group included 100 asymptomatic volunteers with matching age and gender. Coronal and sagittal parameters were measured on the anteroposterior and lateral radiographs of the whole spine, including lumbar lordosis (LL), pelvic incidence (PI), sacral slope (SS), pelvic tilt (PT), thoracic kyphosis (TK), and sagittal balance (SVA). The cases were classified into four types by the apex position of lumbar lordosis (type I, L5 or the L4-5 intervertebral space; type II, bottom or middle of L4 ; type III, upper part of L4 or the intervertebral space between L3 and L4 ; type IV, L3 or more high level), and divided into three groups by PI; namely, a low PI group (PI < 40°), a medium PI group (40° ≤ PI < 50°), and a high PI group (PI ≥ 50°). The sagittal parameters, especially PI, were compared between the LDH group and the control group. Correlations between the parameters in the LDH group were analyzed. RESULTS: The PI value of the LDH group was not different from that of the control group (46.1° ± 10.0° vs 47.2° ± 8.8°, P > 0.05). The LDH group showed lower average LL, SS, and TK (P < 0.01), as well as higher PT and SVA compared with the control group (P < 0.01). The LL (34.4° ± 15.3° vs 50.8° ± 10.2°) and SVA (21.6 ± 53.6 mm vs - 18.4 ± 32.8 mm) showed a significant difference (P < 0.01); LL was correlated with PI, SS, PT, TK and SVA (P < 0.01); and SVA was also correlated with the parameters above (P < 0.01) except PI (P > 0.05), and the lordosis apex tended to be higher. The distributions of PI groups between the LDH group and the control group were not different. Pairwise correlations were found among LL, PI, SS, and PT. In addition, TK and SVA were correlated with LL, SS, and PT. CONCLUSIONS: There is no difference in PI between young Chinese patients with lumbar disc herniation and the normal population. Young LDH patients may present flat lumbar and thoracic curves, as well as lower sacral slope. The anteversion sagittal imbalance is regulated by both the spine and the pelvis.

[Determination of 20 Trace Elements in the Blood Collection Tubes with ICP-MS].

To investigate the contamination of blood collection tubes, 20 trace elements (Al, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Se, Mo, Cd, Sn, Sb, Ba, W, Hg, Tl, Pb) in 13 different types of blood collection tube were studied with ICP-MS method. The lixivium of H(2)O and 10% HNO(3) were measured with ICP-MS, and then the contamination coming from the blood collection tube is specified. According to the concentration range of human blood, plasma and serum from recently published literature, this report presents a detailed analysis of capable trace elements for each blood collection tube. The results showed that, tube No.1 is capable to analyze 18 trace elements in the human serum; tube No.6 is capable to analyze 15 trace elements in the human plasma; tube No. 13 is capable to analyze 17 trace elements in the human blood. But we still should be aware that, the elements Sb and W in tube No.1, the elements V, Cr, Ni, and Sb in tube No.6, and the elements Al, Sb and W in tube No.13, are in the same magnitude of the normal trace element concentration range in the human serum, plasma and blood. They might affect the testing results. The serum collected from the same volunteer by tube No.1 and tube No.3 were compared here, the results show that, almost each trace element concentration of human serum from tube No.1 is lower than from tube No.3, especially for elements Al, V, Cr, Mn, As, Sn, and Sb. The results indicate that the blood collection tubes show great impact on determination of trace element.

Fibrinogen alpha chain precursor and apolipoprotein A-I in urine as biomarkers for noninvasive diagnosis of calcium oxalate nephrolithiasis: a proteomics study.

UNLABELLED: Calcium oxalate nephrolithiasis is the most common urological disease, but noninvasive and convenient methods of diagnosis are rarely available. OBJECTIVE: The present study aimed to identify potential urine biomarkers for noninvasive diagnosis of CaOx nephrolithiasis. METHODOLOGY: Urine samples from 72 patients with CaOx nephrolithiasis and 30 healthy controls were collected and proteomics analysis was performed using matrix-assisted laser desorption/ionization-time of flight-mass spectrometer (MALDI-TOF-MS). RESULTS: Thirteen proteins/peptides displayed statistically significant differences. The peptides of m/z 1207.23 and 2773.86 were selected by the genetic algorithm (GA) to build a possible diagnostic model. The area under the curve of m/z 1207.23 and 2773.86 was 0.936 and 0.987, respectively. The diagnostic model in distinguishing patients and healthy subjects showed 100% sensitivity and specificity. The peak at m/z 2773.86 was identified as fibrinogen alpha chain (FGA) with the sequence G.EGDFLAEGGGVR.G, and the peak at m/z 2773.86 was identified as apolipoprotein A-I (apoA-I) with the sequence L.PVLESFKVSFLSALEEYTKKLNTQ. CONCLUSION: The study results strongly suggested that urinary FGA and apoA-I are highly sensitive and specific biomarkers for noninvasive diagnosis of CaOx nephrolithiasis.

[Identification of Streptococcus mutans in carious patients' saliva samples by MALDI-TOF mass spectrometry].

OBJECTIVE: To identify Streptococcus mutans (S. mutans) in carious patients' saliva using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), and to establish a faster and more accurate method to identify S. mutans. METHODS: In this study, a total of 90 carious patients from Department of Endodontics of Peking University School of Stomatology were recruited. All these patients' saliva was collected. After extracting the protein of the samples, they were identified by MALDI-TOF MS. The composite profile was analyzed using BioExplorer 1.0 software. The scores ≥ 25 were considered as S. mutans, whereas the scores <25 were as considered as non S. mutans. Finally, these results were compared with 16S rDNA sequencing to figure out the sensitivity and concordance rate, respectively. RESULTS: The sensitivity of MALDI-TOF MS was 96.0%, and the concordance rate compared with 16S rDNA sequencing was as high as 98.7%. CONCLUSION: MALDI-TOF MS is high throughput, rapid and easy to perform in comparison to other conventional methods. It has a high sensivity and concordance rate. Thus, MALDI-TOF MS can serve as an effective tool for identification of S. mutans.