Does urinary metabolite signature act as a biomarker of post-stroke depression?

Background: It is difficult to conduct the precise diagnosis of post-stroke depression (PSD) in clinical practice due to the complex psychopathology of depressive disorder. Several studies showed that gas chromatography-mass spectrometry (GC-MS)-identified urinary metabolite biomarkers could significantly discriminate PSD from stroke survivors. Methods: A systematic review was performed for the keywords of "urinary metabolite" and "PSD" using Medline, Cochrane Library, Embase, Web of Science, PsycINFO, Wanfang, CNKI, CBM, and VIP database from inception to 31 March 2022. Results: Four related studies were included in the review. Differential urinary metabolites including lactic acid, palmitic acid, azelaic acid, and tyrosine were identified in all the included studies. As a significant deviation in the metabolite biomarker panel, glyceric acid, azelaic acid, phenylalanine, palmitic acid, pseudouridine, and tyrosine were found in at least 2 included studies, which indicated good potential for the differentiation of PSD. Conclusion: The systematic review provided evidence that differential urinary metabolites analyzed by the GC-MS-based approach might be used as a biomarker for the diagnosis and prognosis of PSD.

Bacterial-mediated RNAi and functional analysis of Natalisin in a moth.

The neuropeptide natalisin (NTL) has been determined to play essential roles in reproduction in two Diptera and one Coleoptera species. Whether NTL has similar or even different functions in Lepidoptera remains to be determined. Here, we cloned the NTL transcript in the common cutworm moth Spodoptera litura. This transcript encodes a 438-amino acid protein. Twelve putative Sl-NTL neuropeptides were defined by cleavage sites. These NTL peptides share a DDPFWxxRamide C-terminal motif. The expressions of Sl-NTL is low during the egg and larval stages, which increased to a higher level during the pupal stage, and then reached the maximum during the adult stage. Moreover, the expression pattern during the pupal stage is similar between sexes while during the adult stage, it is dimorphic. To explore the function of Sl-NTL and assess its potential as a target for pest control, we knocked down the expression of Sl-NTL in both sexes by using bacteria-mediated RNAi. This technique significantly down regulated (reduced up to 83%) the expression of Sl-NTL in both sexes. Knocking down Sl-NTL expression did not significantly affect its development, survival and morphology but significantly reduced adults' reproductive behavior (including female calling, male courtship, mating and remating patterns and rates) and reproductive output (offspring gain reduced more than 70%).

Caspr1 Facilitates sAPPα Production by Regulating α-Secretase ADAM9 in Brain Endothelial Cells.

The expression of contactin-associated protein 1 (Caspr1) in brain microvascular endothelial cells (BMECs), one of the major cellular components of the neurovascular unit (NVU), has been revealed recently. However, the physiological role of Caspr1 in BMECs remains unclear. We previously reported the nonamyloidogenic processing of amyloid protein precursor (APP) pathway in the human BMECs (HBMECs). In this study, we found Caspr1 depletion reduced the levels of soluble amyloid protein precursor α (sAPPα) in the supernatant of HBMECs, which could be rescued by expression of full-length Caspr1. Our further results showed that ADAM9, the α-secretase essential for processing of APP to generate sAPPα, was decreased in Caspr1-depleted HBMECs. The reduced sAPPα secretion in Caspr1-depleted HBMECs was recovered by expression of exogenous ADAM9. Then, we identified that Caspr1 specifically regulates the expression of ADAM9, but not ADAM10 and ADAM17, at transcriptional level by nuclear factor-κB (NF-κB) signaling pathway. Caspr1 knockout attenuated the activation of NF-κB and prevented the nuclear translocation of p65 in brain endothelial cells, which was reversed by expression of full-length Caspr1. The reduced sAPPα production and ADAM9 expression upon Caspr1 depletion were effectively recovered by NF-κB agonist. The results of luciferase assays indicated that the NF-κB binding sites are located at -859 bp to -571 bp of ADAM9 promoter. Taken together, our results demonstrated that Caspr1 facilitates sAPPα production by transcriptional regulation of α-secretase ADAM9 in brain endothelial cells.

Review of Clinical Studies of the Treatment of Ulcerative Colitis Using Acupuncture and Moxibustion.

Background. Clinical studies suggest that acupuncture and moxibustion therapy in ulcerative colitis (UC) can regulate bowel inflammation, and these treatments have the advantages of low rates of adverse reactions and recurrence as well as good long-term efficacy. We reviewed the current status of clinical studies of the treatment. Methods. Randomized controlled trials (RCTs) using the therapy as the major intervention for treating UC were included from 1995 to 2015. The extracted data mainly included diagnostic standards, treatment methods, selection of acupoints, treatment times and courses, and efficacy determination criteria. Results. The use of diagnostic standards and efficacy criteria lacked unification and standardization. There were two main groups: acupuncture and moxibustion therapy combined with drug treatment and the use of all types of acupuncture and moxibustion therapy alone or in combination. The acupoint compositions included distal-proximal point combinations, back-shu point and front-mu point combinations, and acupuncture through meridians. The treatment courses in all the clinical trials had large variations. Conclusion. The treatment of UC in the examined articles was mainly based on the classical theory. However, many links of the clinical regimen design were still lacking, which affected the repeatability of the clinical studies and the accuracy of the clinical conclusions.

RNA Interference in Moths: Mechanisms, Applications, and Progress.

The vast majority of lepidopterans, about 90%, are moths. Some moths, particularly their caterpillars, are major agricultural and forestry pests in many parts of the world. However, some other members of moths, such as the silkworm Bombyx mori, are famous for their economic value. Fire et al. in 1998 initially found that exogenous double-stranded RNA (dsRNA) can silence the homolog endogenous mRNA in organisms, which is called RNA interference (RNAi). Soon after, the RNAi technique proved to be very promising not only in gene function determination but also in pest control. However, later studies demonstrate that performing RNAi in moths is not as straightforward as shown in other insect taxa. Nevertheless, since 2007, especially after 2010, an increasing number of reports have been published that describe successful RNAi experiments in different moth species either on gene function analysis or on pest management exploration. So far, more than 100 peer-reviewed papers have reported successful RNAi experiments in moths, covering 10 families and 25 species. By using classic and novel dsRNA delivery methods, these studies effectively silence the expression of various target genes and determine their function in larval development, reproduction, immunology, resistance against chemicals, and other biological processes. In addition, a number of laboratory and field trials have demonstrated that RNAi is also a potential strategy for moth pest management. In this review, therefore, we summarize and discuss the mechanisms and applications of the RNAi technique in moths by focusing on recent progresses.

Cystatin C Shifts APP Processing from Amyloid-ß Production towards Non-Amyloidgenic Pathway in Brain Endothelial Cells.

Amyloid-ß (Aß), the major component of neuritic plaques in Alzheimer's disease (AD), is derived from sequential proteolytic cleavage of amyloid protein precursor (APP) by secretases. In this study, we found that cystatin C (CysC), a natural cysteine protease inhibitor, is able to reduce Aß40 secretion in human brain microvascular endothelial cells (HBMEC). The CysC-induced Aß40 reduction was caused by degradation of ß-secretase BACE1 through the ubiquitin/proteasome pathway. In contrast, we found that CysC promoted secretion of soluble APPα indicating the activated non-amyloidogenic processing of APP in HBMEC. Further results revealed that α-secretase ADAM10, which was transcriptionally upregulated in response to CysC, was required for the CysC-induced sAPPα secretion. Knockdown of SIRT1 abolished CysC-triggered ADAM10 upregulation and sAPPα production. Taken together, our results demonstrated that exogenously applied CysC can direct amyloidogenic APP processing to non-amyloidgenic pathway in brain endothelial cells, mediated by proteasomal degradation of BACE1 and SIRT1-mediated ADAM10 upregulation. Our study unveils previously unrecognized protective role of CysC in APP processing.

Cytotoxicity enhancement in MDA-MB-231 cells by the combination treatment of tetrahydropalmatine and berberine derived from Corydalis yanhusuo W. T. Wang.

AIM: Our previous works have demonstrated that Chinese herb medicine yanhusuo (Corydalis yanhusuo W. T. Wang) has strong anti-cancer proliferation effect in MDA-MB-231 cells. The goal of this study was to find out the synergic cytotoxicity effect of three natural compounds, tetrahydropalmatine (THP), berberine (Ber), and dehydrocorydaline (DHC), isolated from C. yanhusuo W. T. Wang. MATERIALS AND METHODS: The IC50 of THP Ber and DHC in single use, as well as in combination use at fixed ratios and doses was measured by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay. Isobologram, combination index and modified coefficient of drug interaction (CDI) methods were used for evaluation the combination effects of THF! Ber, and DHC in different ratio and concentration. RESULTS: The results indicated that the combination of THP and Ber shown the strongest anti-cancer cell proliferation effect at the ratio of 2:3 (Ber: THF the average CDI value was 0.5795). DHC and THP have additive cytotoxicity in MDA-MB-231 cells. However, there wasn't any synergistic effect between Ber and DHC, and it even exhibited antagonistic effect when the percentage of DHC was >50%. CONCLUSION: Our findings suggested that the combination of THP and Ber might be beneficial for anti-proliferation of MDA-MB-231 breast cancer cells through a significant synergy effect.