The association of prealbumin, transferrin, and albumin with immunosenescence among elderly males.

OBJECTIVE: As people get older, the innate and acquired immunity of the elderly are affected, resulting in immunosenescence. Prealbumin (PAB), transferrin (TRF), and albumin (ALB) are commonly used markers to monitor protein energy malnutrition (PEM). However, their relationship with the immune system has not been fully explored. METHODS: In our study, a total of 93 subjects (≥65 years) were recruited from Tongji Hospital between January 2015 and February 2017. According to the serum levels of these proteins (PAB, TRF, and ALB), we divided the patients into the high serum protein group and the low serum protein group. Then, we compared the percent expression of lymphocyte subsets between two groups. RESULTS: All the low serum protein groups (PAB, TRF, and ALB) had significant decreases in the percentage of CD4+ cells, CD3+CD28+ cells, CD4+CD28+ cells and significant increases in the percentage of CD8+ cells, CD8+CD28- cells. PAB, TRF, and ALB levels revealed positive correlations with CD4/CD8 ratio, proportions of CD4+ cells, CD3+CD28+ cells, CD4+CD28+ cells, and negative correlation with proportions of CD8+ cells, CD8+CD28- cells. CONCLUSIONS: This study suggested PAB, TRF, and ALB could be used as immunosenescence indicators. PEM might accelerate the process of immunosenescence in elderly males.

Cytotoxic indole diterpenoids and rare pyridoxatin atropisomers from the endophytic fungus Tolypocladium sp. SHJJ1.

Phytochemical investigation on the extract of endophytic fungus Tolypocladium sp. SHJJ1 resulted in the identification of a pair of previously undescribed pyridoxatin atropisomers [1 (M/P)] and three new indole diterpenoids (3-5), together with a pair of known pyridoxatin atropisomers [2 (M/P)] and ten known indole diterpenoids (6-15). Their structures, including their absolute configurations were elucidated by extensive spectroscopic analysis, quantum chemical calculations, and X-ray diffraction. Among the undescribed natural products, [1 (M/P)] that two rapidly interconverting atropisomers are the third example to report in the pyridoxatin atropisomers. Except for compounds 1 (M/P) and 2 (M/P), all other compounds were tested for their cytotoxicity using HepG2, A549, and MCF-7 human cell lines. Compound 9 displayed moderate cytotoxicity against the HepG2, A549, and MCF-7 cell lines with IC50 values of 32.39 ± 1.48 µM, 26.06 ± 1.14 µM, and 31.44 ± 1.94 µM, respectively, which was similar to the positive drug cisplatin (with IC50 values of 32.55 ± 1.76 µM, 18.40 ± 1.43 µM, and 27.31 ± 1.22 µM, respectively).

Rare cytochalasans isolated from the mangrove endophytic fungus Xylaria arbuscula.

Four new cytochalasans, arbuschalasins A-D (1-4), along with thirteen known analogues (5-17), were isolated from the solid rice medium of endophytic fungus Xylaria arbuscula. Arbuschalasins A-B feature a rare 5/6/6/6 fused ring system while arbuschalasin D was characterized as the first example of natural cytochalasans that possesses a 5/5/11 fused scaffold. The structures of 1-4 were assigned by spectroscopic data, with their absolute structures being determined by electronic circular dichroism (ECD) calculations. All of the isolates were evaluated against the human colorectal adenocarcinoma cell lines (HCT15). Compounds 6 and 7 showed significant inhibitory effects (IC50 values were 13.5 and 13.4 µM, respectively), being more active than those of the positive control, fluorouracil (103.1 µM).

The effect of glucocorticoids on mortality in severe COVID-19 patients: Evidence from 13 studies involving 6612 cases.

BACKGROUND: Since the start of the coronavirus disease 2019 (COVID-19) pandemic, there is an urgent need for effective therapies for patients with COVID-19. In this study, we aimed to assess the therapeutic efficacy of glucocorticoids in severe COVID-19. METHODS: A systematic literature search was performed across PubMed, Web of Science, EMBASE, and the Cochrane Library (up to June 26, 2021). The literature investigated the outcomes of interest were mortality and invasive mechanical ventilation. RESULTS: The search identified 13 studies with 6612 confirmed severe COVID-19 patients. Our meta-analysis found that using glucocorticoids could significantly decrease COVID-19 mortality (hazard ratio (HR) 0.60, 95% confidence interval (CI) 0.45-0.79, P < .001), relative to non-use of glucocorticoids. Meanwhile, using glucocorticoids also could significantly decrease the risk of progression to invasive mechanical ventilation for severe COVID-19 patients (HR = 0.69, 95% CI 0.58-0.83, P < .001). Compared with using dexamethasone (HR = 0.68, 95% CI 0.50-0.92, P = .012), methylprednisolone use had a better therapeutic effect for reducing the mortality of patients (HR = 0.35, 95% CI 0.19-0.64, P = .001). CONCLUSION: The result of this meta-analysis showed that using glucocorticoids could reduce mortality and risk of progression to invasive mechanical ventilation in severe COVID-19 patients.

Pseudoguaianelactones A-C: three unusual sesquiterpenoids from Lindera glauca with anti-inflammatory activities by inhibiting the LPS-induced expression of iNOS and COX-2.

The pseudoguaianelactones A (1) and B (2), two novel sesquiterpene lactones with an unprecedented [5,7,7] ring system featuring an α-methylene-γ-lactone moiety, together with a new pseudoguaianelactone C (3) were isolated from the roots of Lindera glauca. Pseudoguaianelactones A-C (1-3) inhibited nitric oxide (NO) production, with IC50 values ranging from 1.38 to 4.00 µM. Moreover, all compounds significantly suppressed the production of pro-inflammatory mediators (TNF-α, IL-6, IL-1ß and PGE2) and the protein expression of the enzymes iNOS and COX-2.

Caesalminaxins O-T, cassane diterpenoids from the seeds of Caesalpinia minax and their anti-inflammation.

Six previously undescribed cassane diterpenoids, named caesalminaxins O-T (1-6), together with 28 known compounds (7-34), were isolated from the seeds of Caesalpinia minax Hance. Their structures, including their absolute configurations were elucidated by extensive spectroscopic analysis, X-ray diffraction, and quantum chemical calculations. Among the undescribed diterpenoids, compound 6 that possessed an unusual enol group at C-7 with a highly deshielded 1H NMR signal was the first example in cassane diterpenoids. All of the isolates were evaluated for their inhibitory activity against lipopolysaccharide-activated NO production in RAW264.7 cells. Compound 16 showed moderate inhibitory activity with an IC50 value of 17.3 µM, which was more potent than the positive control (indomethacin, IC50 = 29.7 µM).

A facile and selective approach to the qualitative and quantitative analysis of triterpenoids and phenylpropanoids by UPLC/Q-TOF-MS/MS for the quality control of Ilex rotunda.

Ilex rotunda, in which triterpenoids and phenylpropanoids are major bioactive constituents, has been widely used in traditional Chinese medicines. In this study, a validated UPLC/Q-TOF-MS/MS method was developed to simultaneously identify and quantify the triterpenoids and phenylpropanoids in the stem bark, fruit, leaves, roots and stem xylem of this herbal medicine. A total of seventy triterpenoids and twelve phenylpropanoids were identified with the assistance of the modified mass defect filter and key product ion filter data processing strategies, and forty-eight of them were confirmed by reference substances. Meanwhile, the contents of twelve triterpenoids and three phenylpropanoids in the five plant parts were determined with good linearity (R2 ≥ 0.9993), precision (RSD ≤ 2.04%), repeatability (RSD ≤ 1.99%), stability (RSD ≤ 1.88%) and recovery (96.65-103.17% and RSD ≤ 3.54%). Furthermore, PCA and OPLS-DA methods were employed to visualize the relationships and discrimination of the forty-two stem bark samples from two origins based on the contents of fifteen analytes. Our findings may provide early scientific evidence for quality control and for elucidating the therapeutic principle of Ilex rotunda.

Inhibitory effect of dauricine on inflammatory process following focal cerebral ischemia/reperfusion in rats.

Our previous experimental studies showed that dauricine could protect the brain from ischemic damage, but the underlying mechanisms were unknown. In this study, we investigated the effect of dauricine on the changes of the inflammation process induced by ischemia/reperfusion (I/R). After I/R, the enzyme activity of MPO, the expression of ICAM-1 and the transcription of IL-1beta and TNF-alpha mRNA were all significantly increased (p < 0.01). And after treatment with dauricine, they were all significantly reduced compared to the vehicle-treated I/R group (p < 0.05 or p < 0.01). These results suggest that dauricin attenuates the inflammation process induced by I/R. The neuroprotective effect of dauricine may partly due to the inhibition acute inflammation induced by I/R.

Neuroprotective effect of dauricine after transient middle cerebral artery occlusion in rats: involvement of Bcl-2 family proteins.

Previous studies have shown that the bisbenzyl isoquinoline alkaloid dauricine can protect the brain against ischemic damage. We investigated here whether dauricine could inhibit neuronal apoptosis and modulate Bcl-2 family protein levels in a rat model of transient focal cerebral ischemia. Male Sprague-Dawley rats underwent a 60 min temporary occlusion of the middle cerebral artery (MCAO). Two doses of dauricine (5 and 10 mg/kg as low and high dose respectively) were administered intraperitoneally at 1 hour after MCAO. After neurological deficits were assessed at 3 hours and 24 hours of reperfusion, rats were killed and brain samples were collected. Apoptotic changes were evaluated by TUNEL method. The immunohistochemistry and Western blot were used to assess the protein expressions of Bcl-2 and Bax. RT-PCR was used to determine Bcl-2 and Bax mRNA expressions. Dauricine (5 and 10 mg/kg) treatment improved neurological deficits, diminished DNA fragmentation, increased Bcl-2 expression and reduced Bax expression in the penumbra. The infarct-reducing effects of dauricine may be due, in part, to the inhibition of apoptotic cell death via modulation Bcl-2 family protein in the penumbra.