Hydroxychloroquine administration exacerbates acute kidney injury complicated by lupus nephritis

Background Hydroxychloroquine (HCQ) has been recommended as a basic treatment for lupus nephritis (LN) during this decade based on its ability to improve LN-related renal immune-mediated inflammatory lesions. As a classical lysosomal inhibitor, HCQ may inhibit lysosomal degradation and disrupt protective autophagy in proximal tubular epithelial cells (PTECs). Therefore, the final renal effects of HCQ on LN need to be clarified. Method HCQ was administered on spontaneous female MRL/lpr LN mice with severe proteinuria daily for 4 weeks. Moreover, the MRL/lpr mice with proteinuric LN were subjected to cisplatin-induced or unilateral ischemia/reperfusion (I/R)-induced acute kidney injury (AKI) after 2 weeks of HCQ preadministration. Results As expected, HCQ treatment increased the survival ratio and downregulated the levels of serum creatinine in the mice with LN, ameliorated renal lesions, and inhibited renal interstitial inflammation. Unexpectedly, HCQ preadministration significantly increased susceptibility to and delayed the recovery of AKI complicated by LN, as demonstrated by an increase in PTEC apoptosis and expression of the tubular injury marker KIM-1 as well as the retardation of PTEC replenishment. HCQ preadministration suppressed the proliferation of PTECs by arresting cells in G1/S phase and upregulated the expression of cell cycle inhibitors. Furthermore, HCQ preadministration disrupted the PTEC autophagy-lysosomal pathway and accelerated PTEC senescence. Conclusion HCQ treatment may increase susceptibility and delay the recovery of AKI complicated by LN despite its ability to improve LN-related renal immune-mediated inflammatory lesions. The probable mechanism involves accelerated apoptosis and inhibited proliferation of PTECs via autophagy-lysosomal pathway disruption and senescence promotion.

BOT-5 Chrysanthemum morifolium extract improves doxorubicin-induced cardiomyopathy by suppressing apoptosis in mouse heart

Background: Doxorubicin is widely used for the treatment of various malignant tumors. However, doxorubicin causes cumulative and dose-dependent cardiotoxicity, ranging from occult changes in myocardial structure and function to severe cardiomyopathy and congestive heart failure. Since this problem affects the QOL and survival of cancer patients, solutions for this problem are urgently needed. Recently, it has been reported that Chrysanthemum morifolium extracts (CME) have antioxidant and anti-inflammatory activities. The purpose of this study is to clarify whether CME decreases doxorubicin-induced cardiotoxicity and prevents the development of heart failure. Methods and Results: H9C2 cardiomyoblast cells were treated with CME (0.3, 1 mg/mL) for 2 hours and then stimulated with doxorubicin. After 24 hours incubation, surviving cells were evaluated by MTT assay. CME dose-dependently decreased doxorubicin-induced cardiotoxicity in H9C2 cells. Western blotting showed that CME significantly suppressed doxorubicin-induced increases in four markers of apoptosis: p53, phosphorylated p53, and cleaved caspase-9 and -3. Next, to investigate the effects of CME on doxorubicin-induced cardiomyopathy in vivo, C57BL6 mice were orally administered with CME (400 mg/kg/day) or vehicle daily from 2 days before doxorubicin treatment and then treated once intraperitoneally with doxorubicin (20 mg/kg). The survival ratio of the CME-treated group was significantly higher than that of the vehicle-treated group. Echocardiographic analysis at 7 days after doxorubicin stimulation revealed that CME had significantly improved doxorubicin-induced left ventricular systolic dysfunction. Apoptotic cells in mouse heart tissue were detected by TUNEL assay, which showed that CME significantly suppressed doxorubicin-induced apoptosis. Discussion: These results indicate that CME decreases doxorubicin-induced cardiotoxicity both in vitro and in vivo, suggesting that CME might possess the therapeutic potency to reduce doxorubicin-induced cardiotoxicity in cancer patients. Further studies are required to assess the effectiveness of CME for preventing doxorubicin-induced heart failure in clinical settings.

Enterococcus faecium are associated with the modification of gut microbiota and shrimp post-larvae survival

Background Probiotics are widely used to promote host health. Compared to mammals and terrestrial invertebrates, little is known the role of probiotics in aquatic invertebrates. In this study, eighteen tanks with eight hundred of shrimp post-larvae individuals each were randomly grouped into three groups, one is shrimps administered with E. faecium as probiotic (Tre) and others are shrimps without probiotic-treatment (CK1: blank control, CK2: medium control). We investigated the correlations between a kind of commercial Enterococcus faecium (E. faecium) powder and microbiota composition with function potentials in shrimp post-larvae gut. Results We sequenced the 16S rRNA gene (V4) of gut samples to assess diversity and composition of the shrimp gut microbiome and used differential abundance and Tax4Fun2 analyses to identify the differences of taxonomy and predicted function between different treatment groups. The ingested probiotic bacteria (E. faecium) were tracked in gut microbiota of Tre and the shrimps here showed the best growth performance especially in survival ratio (SR). The distribution of SR across samples was similar to that in PCoA plot based on Bray-Curits and two subgroups generated (SL: SR < 70%, SH: SR ≥ 70%). The gut microbiota structure and predicted function were correlated with both treatment and SR, and SR was a far more important factor driving taxonomic and functional differences than treatment. Both Tre and SH showed a low and uneven community species and shorted phylogenetic distance. We detected a shift in composition profile at phylum and genus level and further identified ten OTUs as relevant taxa that both closely associated with treatment and SR. The partial least squares path model further supported the important role of relevant taxa related to shrimp survival ratio. Conclusions Overall, we found gut microbiota correlated to both shrimp survival and ingested probiotic bacteria (E. faecium). These correlations should not be dismissed without merit and will uncover a promising strategy for developing novel probiotics through certain consortium of gut microbiota.

In Vivo Hypoglycemic Effects, Potential Mechanisms and LC-MS/MS Analysis of Dendropanax Trifidus Sap Extract

Extracts of medicinal plants have been widely used to benefit human health. Dendropanax morbiferus (DM) has been well-studied for its anti-inflammatory and anti-oxidative effects, while Dendropanax trifidus (DT) is a lesser-known ecotype phylogenetically similar to DM, which has received significantly less attention. Studies thus far have primarily focused on leaf and bark extracts of DM, and not much is yet known about the properties of either DM or DT sap. Therefore, here we performed in vivo toxicity and efficacy studies, in order to assess the biological effects of DT sap. To establish a safe dosage range, single dose or two-week daily administrations of various concentrations were performed for ICR mice. Measurements of survival ratio, body/organ weight, blood chemistry, histochemistry and Western blots were performed. A concentration of ≤0.5 mg/g DT sap was found to be safe for long-term administration. Interestingly, DT sap significantly reduced blood glucose in female mice. In addition, increasing concentrations of DT sap decreased phosphorylated (p) insulin receptor substrate (IRS)-1(ser1101)/IRS-1 in liver tissues, while increasing pAMP-activated protein kinase (AMPK)/AMPK in both the liver and spleen. To analyze its components, liquid chromatography-tandem mass spectrometry of DT sap was performed in comparison with Acer saccharum (AS) sap. Components such as estradiol, trenbolone, farnesol, dienogest, 2-hydroxyestradiol and linoleic acid were found to be highly enriched in DT sap compared to AS sap. Our results indicate DT sap exhibits hypoglycemic effects, which may be due to the abundance of the bioactive components.

Evaluation of the Compatibility of Modified Encapsulated Sodium Silicate for Self-Healing of Cementitious Composites

Healing agent carriers play a significant role in defining the performance of the autonomous self-healing system. Particularly, the ability to survive during the mixing process and the release of the healing agent when cracks occur without affecting the mechanical properties of the cementitious composite. Up to now, these issues are still a concern since glass capsules are unable to survive the mixing process, while some types of microcapsules were reported to cause a decrement in strength as well as limited strength recovery. Therefore, this study was twofold, addressing the surface treatment of polystyrene (PS) capsules and the evaluation of the compatibility of the modified capsules for cement-based applications. Secondly, assessing the healing performance of modified PS capsules in cementitious composites. Furthermore, the study also evaluates the potential healing performance due to the synergic effect between the encapsulation method and the autogenous self-healing mechanism. The investigation was carried out by measuring the changes in the pH of pore solution, FTIR analysis, survival ratio, and bonding strength. For self-healing assessment, the compression cracks on the cement paste were created at an early age and the strength recovery was measured at the age of 28 and 56 days. To identify the chemical compounds responsible for the healing process, SEM-EDX tests were conducted. Moreover, the effect of silica fume (SF) on bonding strength and self-healing was also evaluated. Based on the results, the modified PS capsules by roughing approach showed promising performance in terms of survivability, bonding, and recovery. The modified PS capsule increased the strength recovery by about 12.5–15% for 100%OPC and 95%OPC + 5%SF, respectively. The finding observed that the combining of modified PS capsules and the inclusion of SF gave high strength recovery of about 20% compared to 100%OPC without capsules. Thus, the modified PS capsule has a good potential for self-healing of cementitious-based applications.

Treatment Prognosis of Restored Teeth with Crown Lengthening vs. Deep Margin Elevation: A Systematic Review

Crown lengthening surgery and deep margin elevation are two distinct approaches used to manage decayed teeth. This systematic review examined the survival rate of badly decayed teeth when restored using the crown lengthening technique and compared it to the deep margin elevation technique. The search was conducted during July 2020 and then again updated at the end of July 2021, and no restriction concerning publication status and time was applied during the search. Cochrane Database, EBSCO, Scopus, and Medline databases were searched electronically for relevant literature. Google Scholar was used as a secondary source. Predefined inclusion and exclusion criteria were used to select the relevant articles. PRISMA guidelines were followed. The focused PICO question was: ‘Does the crown lengthening technique (I) provide a better survival rate (O) than deep margin elevation technique (C) following the restoration of badly decayed teeth (P).’ A total of six articles were included after performing screening based on the eligibility criteria. Four studies focused on crown lengthening while two focused on deep margin elevation technique. A majority of the studies showed a high risk of bias owing to methodological insufficiencies. Crown lengthening (CL) treated cases showed a change in the free gingival margin at six months post-surgery. A tissue rebound was seen that was correlated to the periodontal biotype. Teeth treated with the deep margin elevation (DME) technique showed high survivability. There is a lack of high-quality trials examining surgical comparisons between CL and DME with long-term follow-up. Patient- and dentist-reported outcomes have not been given adequate consideration in the literature. Based on the limited evidence, it can be concluded that for restorative purposes, crown lengthening surgery can be successful in long-term retention of restored teeth. However, the deep margin elevation technique has a better survival ratio. Future well-designed and executed research will have an effect on the evidence and level of certainty for the best approach to treating severely decayed teeth.

Validating the Effects of Disruptive Technologies using Operational Breakeven Theory, Relative Solvency Ratio and Altman’s Z-score on Selected Firms in Nigeria and India

Disruptive technologies (DT) have featured prominently in almost every human activity since the advent of computerization. The likely effects of DT on economic processes and human professions have and continue to generate fears and debates which spurred this investigation. To break away from the traditional approach the operational breakeven theory and the discriminant analysis techniques of Altman&rsquo;s Z-score, and Enyi&rsquo;s Relative Solvency Ratio were used to examine the relationship between firms&rsquo; market-induced-survival-ratio (MISR) and the disruptive technology gains index (DTGI) of seventy-three firms drawn from Nigeria and India. Descriptive and inferential statistics were used to analyze the data generated. The results showed that a sizeable number of firms has profited from the introduction of disruptive technologies with MISR and DTGI returning a 10% significant relationship while others are still struggling to measure up to the requirements of disruptive technologies in their chosen economic fields. The implication of this is that businesses must brace up and embrace digital transformation if they must stay afloat in this era of disruptive technologies. This study recommends a revolutionary approach to digital transformation in view of the fast pace of global integration while managers and business owners should adopt more pragmatic approach in appraising the operations and finances of a firm for effective results and timely responses to potential business challenges.

Supplementation of Lactobacillus casei reduces the mortality of Bombyx mori larvae challenged by Nosema bombycis

Objective Pebrine, caused by the microsporidium Nosema bombycis, is one of the severe diseases in Thai polyvoltine strains of the silkworm Bombyx mori. Studies showing the presence of Lactobacillus species in the silkworm gut, where the Nosema parasites enter, suggests that these bacteria may have a protective effect. The aim of this study was to investigate the effect of supplementation of Lactobacillus casei on the survival ratio of silkworm larvae challenged with N. bombycis. Results A group of silkworm larvae of the commercial Thai polyvoltine hybrid strain DokBua was supplemented with L. casei on the second day of the 2nd, 3rd, 4th, and 5th instar. When a control group of silkworm larvae were challenged with N. bombycis on the second day of the 4th instar, the survival rate was 68%, but it was 91% for larvae supplemented with L. casei. For those larvae that survived the treatments until pupation, we determined the growth characters larval weight, cocooning ratio, and pupation ratio, and the economic characters cocoon weight and cocoon shell weight. When infected with N. Bombycis, growth characters were significantly higher in larvae also receiving L. casei.

Time-resolved, integrated analysis of clonal genome evolution in parthenogenetic animals and in cancer

Clonal genome evolution is a key aspect for parthenogenetic species and cancer. While many studies describe precise landscapes of clonal evolution in cancer, few studies determine the underlying evolutionary parameters from molecular data, and fewer integrate theory with data. We derived theoretical results linking mutation rate, time, expansion dynamics, transition to recurrence, and survival. With this, we inferred time-resolved estimates of evolutionary parameters from mutation accumulation, mutational signatures and selection. Using this framework we traced the speciation of the rapidly emerging and invasive marbled crayfish to a time window between 1947 and 1996, which is consistent with biological records. In glioblastoma samples, we determined tumor expansion patterns, and tumor cell survival ratio at resection. Interestingly, our results suggest that the expansion pattern in the primary tumor is predictive of the progress and time to recurrence. In addition, tumor cell survival was always higher after resection and was associated with the expansion pattern and time to recurrence. We further observed selection events in a subset of tumors, with longer and purifying-only selection phases in recurrent tumors. In conclusion, our framework allowed a time-resolved, integrated analysis of key parameters in clonally evolving genomes, and provided novel insights into the evolutionary age of marbled crayfish and the progression of glioblastoma.

Application of polymeric dimethylaminoethyl methacrylate based carriers of plasmid DNA for genetic transformation of Ceratodon purpureus moss

Introduction. Genetic engineering in plants is of great importance for agriculture, biotechnology and medicine, and nanomaterials are widely used for genetic engineering. The aim of present study was to evaluate the potential of poly(2-dimethylamino)ethyl methacrylate (DMAEMA)-based comb-like polymers as gene delivery systems in moss Ceratodon purpureus (Hedw.) Brid. protoplasts and determine the level of phytotoxicity of these polymers. Materials and Methods. In order to confirm the formation of complex of poly-DMAEMA carrier with plasmid DNA pSF3, gel retardation assay was used. The PEG-mediated transformation protocol was adapted to transform the protoplasts of C. purpureus moss with poly-DMAEMA carriers. Light microscopy was used to study a toxicity of polymers for moss protoplasts. The level of the polymers toxicity was estimated as IC50 value. Results and Discussion. The formation of pDNA complex with DMAEMA-based carriers took place at 0.03% concentration of the polymers BGA-21, BGA-22(2ph), BG-24, BG-25, BG-26 or 0.1% concentration of the BGA-22 polymer. Poly-DMAEMA carriers were able to deliver plasmid DNA pSF3 into protoplasts of C. purpureus moss. Three stable transformants of C. purpureus were obtained at using BGA-22 polymer, 2 clones – at using BGA-21 carrier, and 1 clone – at using BGA-22(2ph), BG-24, BG-25, BG-26 polymers. The poly-DMAEMA carriers at the working 0.0025% dose were relatively non-toxic for protoplasts of C. purpureus moss. 83.1-88.4% of viable protoplasts of C. purpureus moss were detected after treatment with studied carriers at 0.0025% dose. A survival ratio of protoplasts reached 66.7-72.9% under the effect of these polymers at 0.025% dose, which is 10 times higher than their working concentration. The IC50 value of poly-DMAEMA carriers was in the range of 0.113-0.164%, that was approximately 10 times higher than that of the PEG-6000 used for gene delivery in plants. Conclusion. Novel synthetic poly-DMAEMA carriers delivered the gene of interest into moss C. purpureus protoplasts and possessed a low phytotoxicity. Thus, these carriers can be useful for gene delivery into plant cells.