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Author(s):  
Emmanuel Reyes-Uribe ◽  
Marco Antonio Hernández-Bedolla ◽  
Joel Salazar-Flores ◽  
Erandis Dheni Torres-Sánchez

La enfermedad renal o de riñón es una anormalidad funcional de los riñones que tiene implicaciones en la salud. El daño agudo de riñón y la enfermedad renal crónica presentan una elevada incidencia en México y representan un problema de salud pública con repercusiones económicas importantes. El diagnóstico oportuno de la enfermedad renal tendría un efecto positivo en la eficacia del tratamiento y en el pronóstico de la enfermedad. KIM-1(Kidney Injury Molecule-1) es una glicoproteína que actúa como receptor para fosfatidilserina y TIM-4 (T-Cell Immunoglobulin and Mucin Domain-4); aunque se expresa en diferentes células y tejidos, su expresión se produce principalmente en células del epitelio tubular proximal de las nefronas. En personas sanas KIM-1 no se expresa, pero durante el daño en las células epiteliales tubulares, se sobreexpresa y su fracción soluble es secretada en orina y/o filtrada a la sangre, lo que aumenta su concentración y permite su detección en estos fluidos; por esta razón, se ha propuesto como un biomarcador de daño renal. En fases tempranas, KIM-1 tiene una función protectora ante el insulto renal, pero su expresión sostenida en células del epitelio tubular se ha asociado con la enfermedad renal crónica y la fibrosis renal. En esta revisión, describimos la estructura de KIM-1, su expresión y su función tanto en el sistema inmunológico como en la enfermedad renal.


2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Yuzhu Dong ◽  
Dan Sun ◽  
Yan Wang ◽  
Qian Du ◽  
Ying Zhang ◽  
...  

Abstract Background Bacterial infections are common complications in patients with cirrhosis or liver failure and are correlated with high mortality. Clinical practice guideline (CPG) is a reference used to help clinicians make decisions. This systematic appraisal aimed to evaluate the methodological quality and summarize the recommendations of reported CPGs in these patients. Methods We systematically searched CPGs published from 2008 to 2019. The methodological quality of the included CPGs was assessed using the AGREE II instrument. We extracted and compared recommendations for prophylactic and empirical treatment strategies. Results Fourteen CPGs with a median overall score of 56.3% were included. The highest domain score was Clarity of Presentation (domain 4, 85.4%), and the lowest was for Stakeholder Involvement (domain 2, 31.3%). Three CPGs had an overall score above 80%, and 6 CPGs had a score above 90% in domain 4. Prophylaxis should be strictly limited to patients with varicose bleeding, low ascites protein levels and a history of spontaneous bacterial peritonitis. Fluoroquinolones (norfloxacin and ciprofloxacin), third-generation cephalosporins (G3) (ceftriaxone and cefotaxime) and trimethoprim–sulfamethoxazole (SXT) are recommended for preventing infections in patients with cirrhosis or liver failure. G3, β-lactam/β-lactamase inhibitor combinations (BLBLIs) and carbapenems are recommended as the first choice in empirical treatment according to local epidemiology of bacterial resistance. Conclusions The methodological quality of CPGs focused on patients with cirrhosis or liver failure evaluated by the AGREE II instrument is generally poor. Three CPGs that were considered applicable without modification and 6 CPGs that scored above 90% in domain 4 should also be paid more attention to by healthcare practitioners. Regarding recommendations, norfloxacin, ciprofloxacin, ceftriaxone, cefotaxime, and SXT are recommended for prophylactic treatment appropriately. G3, BLBLIs, and carbapenems are recommended for use in empirical treatment strategies.


2021 ◽  
Vol 12 (2) ◽  
pp. 332
Author(s):  
Nur Hikmah Buchair ◽  
Ridwan Amiruddin ◽  
Indar Indar

Penderita Diabetes Melitus umumnya memiliki kualitas hidup yang buruk dibandingkan dengan orang yang tanpa penyakit sehingga membutuhkan perawatan diabetes yang tepat melalui intervensi perilaku berupa dukungan pendidikan dan konseling untuk mengaktifkan penderita diabetes untuk mengelola penyakitnya. Penelitian ini bertujuan untuk mengetahui pengaruh konseling dalam home care terhadap kualitas hidup penderita Diabetes Mellitus Tipe 2. Penelitian ini dilaksanakan di wilayah kerja Puskesmas Talise dan wilayah kerja Puskesmas Birobuli Kota Palu. Desain penelitian adalah Eksperimen Semu dengan jumlah sampel sebanyak 40 responden yang dipilih secara acak. Analisis data menggunakan Uji Beda Dua Mean yaitu Uji Wilcoxon dan Uji Beda Dua Mean Independen yaitu Uji Mann Whitney. Hasil penelitian menunjukkan ada pengaruh konseling home care terhadap kualitas hidup penderita DM baik pada Domain 1 (Kesehatan Fisik), Domain 2 (Kondisi Psikologis), Domain 3 (Hubungan Sosial), Domain 4 (Lingkungan) dimana skor rata- rata (mean) sebelum intervensi adalah 60,55 dengan standar deviasi 2,605 meningkat menjadi 71,35 dengan standar deviasi 4,107 setelah intervensi. Secara statistik terjadi perbedaan kualitas hidup sebelum dan setelah diberikan konseling dengan nilai p= 0,000 (p<0,05) yang berarti bahwa konseling home care efektif diberikan pada penderita DM untuk meningkatkan kualitas hidup penderita DM.


Author(s):  
DongGun Kim ◽  
Song-Ho Chong ◽  
Seokmin Shin ◽  
Sihyun Ham
Keyword(s):  

Author(s):  
Yaya Wang ◽  
Lian Li ◽  
Qiang Wei ◽  
Rongrong Chai ◽  
Qingqiang Yao ◽  
...  

Osteoarthritis (OA) is now becoming the main disease that affects public health. There is no specific medicine used for OA in clinical application until now. Recently, several studies demonstrated that OA is closely related to the complement system, and some complement regulators such as N-terminal non-collagenous domain 4 (NC4) aimed at alleviating OA have shown a promising therapeutic effect. However, targeting ability is the main limitation for NC4. In this study, a fusion protein named heparin-binding domain-N-terminal non-collagenous domain 4 (HB-NC4) was proposed to solve this problem, which could provide a better way for OA treatment. First, HB-NC4 plasmid was constructed using ClonExpress II one-step ligation kit method. And Escherichia coli BL21 was utilized to express the fusion protein, Ni2+-sepharose, and a desalting gravity column were introduced to purify HB-NC4. The results showed that 0.84 mg HB-NC4 could be obtained from a 1 L culture medium with a purity higher than 92.6%. Then, the hemolytic assay was introduced to validate the anti-complement activity of HB-NC4; these results demonstrated that both HB-NC4 and NC4 had a similar anti-complement activity, which indicated that heparin-binding (HB) did not affect the NC4 structure. Targeting ability was investigated in vivo. HB-NC4 showed a higher affinity to cartilage tissue than NC4, which could prolong the retention time in cartilage. Finally, the destabilization of the medial meniscus (DMM) model was applied to investigate HB-NC4 pharmacodynamics in vivo. The results indicated that HB-NC4 significantly slowed cartilage degradation during the OA process. In summary, compared with NC4, HB-NC4 had better-targeting ability which could improve its therapeutic effect and prolonged its action time. It could be used as a new complement regulator for the treatment of OA in the future.


Nutrients ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 2648
Author(s):  
Shila Minari Hargreaves ◽  
Eduardo Yoshio Nakano ◽  
Heesup Han ◽  
António Raposo ◽  
Antonio Ariza-Montes ◽  
...  

This study aimed to evaluate the general quality of life (QoL) of Brazilian vegetarians. A cross-sectional study was conducted with Brazilian vegetarian adults (18 years old and above). Individuals were recruited to participate in a nationwide online survey that comprised the WHOQOL-BREF as well as sociodemographic and characterization questions related to vegetarianism. The WHOQOL-BREF is composed of 24 items which are divided into four domains (domain 1: physical health; domain 2: psychological well-being; domain 3: social relationships; and domain 4: environment), plus two general items which were analyzed separately, totaling 26 items. The answers from the questionnaire were converted into scores with a 0–100 scale range, with separate analyses for each domain. Results were compared among groups based on the different characteristics of the vegetarian population. A total of 4375 individuals completed the survey. General average score results were 74.67 (domain 1), 66.71 (domain 2), 63.66 (domain 3) and 65.76 (domain 4). Vegans showed better scores when compared to the other vegetarians, except in domain four, where the statistical difference was observed only for semi-vegetarians (lower score). Individuals adopting a vegetarian diet for longer (>1 year) showed better results for domains one and two, with no difference for the other domains. Having close people also adopting a vegetarian diet positively influenced the results for all domains. On the other hand, it was not possible to distinguish any clear influence of the motivation for adopting a vegetarian diet on the scores’ results. Adopting a vegetarian diet does not have detrimental effects on one’s QoL. In fact, the more plant-based the diet, and the longer it was adopted, the better the results were.


Author(s):  
Filip Radom ◽  
Clemens Vonrhein ◽  
Peer R. E. Mittl ◽  
Andreas Plückthun

The members of the human epidermal growth factor receptor (HER) family are among the most intensely studied oncological targets. HER3 (ErbB3), which had long been neglected, has emerged as a key oncogene, regulating the activity of other receptors and being involved in progression and tumor escape in multiple types of cancer. Designed ankyrin-repeat proteins (DARPins) serve as antibody mimetics that have proven to be useful in the clinic, in diagnostics and in research. DARPins have previously been selected against EGFR (HER1), HER2 and HER4. In particular, their combination into bivalent binders that separate or lock receptors in their inactive conformation has proved to be a promising strategy for the design of potent anticancer therapeutics. Here, the selection of DARPins targeting extracellular domain 4 of HER3 (HER3d4) is described. One of the selected DARPins, D5, in complex with HER3d4 crystallized in two closely related crystal forms that diffracted to 2.3 and 2.0 Å resolution, respectively. The DARPin D5 epitope comprises HER3d4 residues 568–577. These residues also contribute to interactions within the tethered (inactive) and extended (active) conformations of the extracellular domain of HER3.


2021 ◽  
Author(s):  
Hala Ouzon-Shubeita ◽  
Lillian Feigang Schmaltz ◽  
Seongmin Lee

G:T mismatches, the major mispairs generated during DNA metabolism, are repaired in part by mismatch-specific DNA glycosylases such as methyl-CpG-binding domain 4 (MBD4) and thymine DNA glycosylase (TDG). Mismatch-specific DNA glycosylases must discriminate the mismatches against million-fold excess correct base pairs. MBD4 efficiently removes thymine opposite guanine but not opposite adenine. Previous studies have revealed that the substrate thymine is flipped out and enters the catalytic site of the enzyme, while the estranged guanine is stabilized by Arg468 of MBD4. To gain further insights into mismatch discrimination mechanism of MBD4, we assessed the glycosylase activity of MBD4 toward various base pairs. In addition, we determined a crystal structure of MBD4 bound to T:O6-methylguanine-containing DNA, which suggests the O6 and N2 of purine and the O4 of pyrimidine are required to be a substrate for MBD4. To understand the role of the Arg468 finger in catalysis, we evaluated the glycosylase activity of MBD4 mutants, which revealed the guanidinium moiety of Arg468 may play an important role in catalysis. D560N/R468K MBD4 bound to T:G mismatched DNA shows that the side chain amine moiety of the Lys stabilizes the flipped-out thymine by a water-mediated phosphate pinching, while the backbone carbonyl oxygen of the Lys engages in hydrogen bonds with N2 of the estranged guanine. Comparison of various DNA glycosylase structures implies the guanidinium and amine moieties of Arg and Lys, respectively, may involve in discriminating between substrate mismatches and nonsubstrate base pairs.


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