Mesenchymal Stem Cell-Derived Exosomes Attenuate Murine Cytomegalovirus-Infected Pneumonia via NF-κB/NLRP3 Signaling Pathway.

Reactivation and infection with cytomegalovirus (CMV) are frequently observed in recipients of solid organ transplants, bone marrow transplants, and individuals with HIV infection. This presents an increasing risk of allograft rejection, opportunistic infection, graft failure, and patient mortality. Among immunocompromised hosts, interstitial pneumonia is the most critical clinical manifestation of CMV infection. Recent studies have demonstrated the potential therapeutic benefits of exosomes derived from mesenchymal stem cells (MSC-exos) in preclinical models of acute lung injury, including pneumonia, ARDS, and sepsis. However, the role of MSC-exos in the pathogenesis of infectious viral diseases, such as CMV pneumonia, remains unclear. In a mouse model of murine CMV-induced pneumonia, we observed that intravenous administration of mouse MSC (mMSC)-exos reduced lung damage, decreased the hyperinflammatory response, and shifted macrophage polarization from the M1 to the M2 phenotype. Treatment with mMSC-exos also significantly reduced the infiltration of inflammatory cells and pulmonary fibrosis. Furthermore, in vitro studies revealed that mMSC-exos reversed the hyperinflammatory phenotype of bone marrow-derived macrophages infected with murine CMV. Mechanistically, mMSC-exos treatment decreased activation of the NF-κB/NLRP3 signaling pathway both in vivo and in vitro. In summary, our findings indicate that mMSC-exo treatment is effective in severe CMV pneumonia by reducing lung inflammation and fibrosis through the NF-κB/NLRP3 signaling pathway, thus providing promising therapeutic potential for clinical CMV infection.

The longer, the better ? Longer left-sided prolonged intermittent theta burst stimulation in patients with major depressive disorder: A randomized sham-controlled study.

BACKGROUND: Prolonged intermittent theta-burst stimulation (iTBS) is effective for major depressive disorder (MDD). However, whether longer piTBS treatment in a single session could have antidepressant efficacy remains elusive. Therefore, this double-blind, randomized, sham-controlled study aimed to investigate the antidepressant efficacy of 2 daily piTBS sessions for treating MDD patients with a history of poor responses to at least 1 adequate antidepressant trial in the current episode. METHODS: All patients received 2 uninterrupted sessions per day for 10 weekdays (i.e., 2 weeks; a total of 20 sessions). Seventy-two patients were recruited and 1:1:1 randomly assigned to one of three groups: piTBS (piTBSx2), 10-Hz rTMS (rTMSx2), or sham treatment (shamx2, randomly assigned to piTBS or rTMS). 10-Hz rTMS group was included as an active comparison group to enhance assay sensitivity. RESULTS: piTBSx2 group had significantly more responders at week 2 than shamx2 group, but it did not yield better antidepressant effects regarding the %depression changes. The changes of antidepressant scores were not different among the three groups at week 1 (-26.2% vs. -23.3% vs. -22.%) or at week 2 (-34.1% vs. -37.1% vs. -30.1%). Longer treatment duration did not result in stronger placebo effects [sham(piTBS)x2: - 31.7% vs. sham(rTMS)x2: - 26.7%]. CONCLUSION: The present sham-controlled study confirmed that piTBS is an effective antidepressant option, but found no evidence to support that longer piTBS treatment duration resulted in more rapid or better antidepressant effects. A high placebo effect was observed, but longer treatment duration of brain stimulation was not linearly associated with stronger placebo effects.

Cortical excitatory and inhibitory correlates of the fronto-limbic circuit in major depression and differential effects of left frontal brain stimulation in a randomized sham-controlled trial.

BACKGROUND: Major depressive disorder (MDD), particularly treatment-resistant ones, is associated with abnormal fronto-limbic glucose metabolism. 10-Hz repetitive transcranial magnetic stimulation (rTMS) over left prefrontal cortex (PFC) is believed to normalize the abnormal metabolism to treat depression. However, the exact molecular mechanisms underlying the mood circuit of depressed brains and whether brain stimulation techniques regulate the underlying molecules remain elusive. METHODS: Whole-brain glucose metabolism and cortical excitatory and inhibitory markers including P30, N45, P60, N100, and LICI (long-interval cortical inhibition) of TMS-evoked potentials from left DLPFC were measured in 40 subjects with MDD patients. The neurophysiological markers were repeated immediately after 1st session of left PFC rTMS, intermittent theta-burst stimulation (iTBS), and sham (randomly assigned). RESULTS: Brain glucose metabolism in the limbic structures significantly correlated with left PFC P30 (mainly GABA-A and glutamate receptor mediated) and with LICI (mainly GABA-B receptor mediated inhibition) (FWE-corrected p < 0.001). Correlations between other neurophysiological markers (left PFC N45, P60, and N100) and posterior cingulate cortex, a key region in the default mode network, were also noted. One session of rTMS significantly decreased left PFC P60 (mainly glutamate receptor mediated), while a significant group effect was found for LICI (iTBS < sham). CONCLUSION: The first study showed that the underlying molecular mechanisms of fronto-limbic circuit of MDD brains involved glutamatergic excitation and GABAergic inhibition at specific time points. In addition, one session of rTMS mainly modulated glutamatergic neurotransmission at left PFC, while the mechanisms of iTBS might involve GABA-B receptor mediated inhibition. CLINICAL TRIALS REGISTRY NUMBER: UMIN000044951.

The complete mitochondrial genome of Nysius fuscovittatus (Hemiptera: Lygaeidae).

Here, we sequenced and annotated the complete mitochondrial genome (mitogenome) of Nysius fuscovittatus (Hemiptera: Lygaeidae). This mitogenome was 14575 bp long, including 13 protein-coding genes (PCGs), 22 transfer RNA genes (tRNAs), 2 ribosomal RNA unit genes (rrnL and rrnS), and a putative control region. All genes were arranged in the same order as that of most true bugs. Eleven PCGs started with a typical ATN, and the remaining two PCGs started with TTA (nad4L) and TTG (cox1). The N. fuscovittatus mitogenome with an A + T content of 76.42% showed a positive AT-skew (0.15) and a negative GC-skew (-0.15). With the exception of trnS1 that lacked the dihydrouridine arm, all tRNAs had a typical cloverleaf secondary structure. Phylogenetic analysis based on the concatenated nucleotide sequences of the 13 PCGs showed that N. fuscovittatus clustered with other three Lygaeidae species.

The value of serum visfatin in predicting in-stent restenosis of drug-eluting stents.

OBJECTIVE: This study aims to determine the association between serum visfatin level and in-stent restenosis (ISR) after percutaneous coronary intervention (PCI) using drug-eluting stents (DES). METHODS: A total of 460 patients with stable coronary heart disease who underwent DES placement were included. According to the results of coronary angiography 1year after PCI, 62 patients diagnosed as ISR were enrolled into the ISR group and 398 patients without ISR were recruited into the control group. Baseline clinical data were collected, and serum visfatin level was measured using ELISA method. RESULTS: The serum visfatin levels before PCI were not different between ISR and control groups (P=0.41). However, visfatin level after PCI in the ISR group was significantly higher than in the control group [(30.2±8.6) ng/ml vs. (22.6±7.9) ng/ml, P<0.01]. In multivariate logistic regression, the independent predictors for ISR included post-procedural visfatin level (odds ratio [OR]: 2.08, 95% confidence interval [CI]: 1.19-3.65), type 2 diabetes (OR: 2.30, 95% CI: 1.10-4.79), reference vessel diameter (OR: 0.79, 95% CI: 0.63-0.98), stent length (OR: 1.52, 95% CI: 1.05-2.21) and stent diameter (OR: 0.67, 95% CI: 0.51-0.88). ROC curve analysis indicated that the area under the curve for post-procedural visfatin in predicting ISR was 0.82 (95% CI: 0.77-0.86), with the optimal cut-off value of 25.9ng/ml showing a sensitivity of 84.0% and a specificity of 69.3%. CONCLUSION: Increased serum visfatin level after DES placement is independently associated with ISR. Serum visfatin may be useful in the prediction of ISR.

Bacterial communities associated with an occurrence of colored water in an urban drinking water distribution system.

This study aimed to investigate bacterial community in an urban drinking water distribution system (DWDS) during an occurrence of colored water. Variation in the bacterial community diversity and structure was observed among the different waters, with the predominance of Proteobacteria. While Verrucomicrobia was also a major phylum group in colored water. Limnobacter was the major genus group in colored water, but Undibacterium predominated in normal tap water. The coexistence of Limnobacter as well as Sediminibacterium and Aquabacterium might contribute to the formation of colored water.

Overcoming disparities in diabetes care: eight years' experience changing the diabetes care system in Changhua, Taiwan.

AIMS: To enhance the universal coverage of quality diabetes care and overcome disparities in care among different care-provider levels by changing the diabetes care system in Changhua, Taiwan. METHODS: The Changhua Diabetes Shared Care program's second stage commenced in 2004. Two levels of diabetes care were proposed to facilitate physician participation via advocating the more attainable goals of diabetes care. The empowerment processes were differentiated into hospital-level and primary-care-clinic-level. The community multidisciplinary care teams took the scale of the practices into consideration, and several measures were applied to ameliorate the shared care network. The implementation support team from the health authority initiated in-person, one-on-one contacts with physicians to tailor collaboration activities to the individual primary care settings. The program's performance (2004-2012) was evaluated according to the RE-AIM model's five dimensions. RESULTS: There was substantial improvement in diabetes care quality across all dimensions and the proportion of attaining all goals significantly grew. CONCLUSIONS: The program achieved its primary goal of enhancing the universal coverage of quality diabetes care and overcoming disparities among different levels of care providers.

Triterpenoids from Angiopteris palmiformis.

Two new fernane triterpenoids, 7alpha-hydroxyfern-8-en-11-one (1) and 11beta-hydroxyfern-8-en-7-one (2), and two new filicane triterpenoids, 3beta-hydroxyfilic-4(23)-ene (3) and filicenol (5), together with one known filicane-type triterpenoid, 3alpha-hydroxyfilic-4(23)-ene (4), were isolated from the methyl alcohol extract of the leaves of Angiopteris palmiformis. Their structures were elucidated on the basis of extensive analyses of their spectroscopic data (NMR, MS, IR) and comparison with spectroscopic data in the literature.