Dynamic immune and exosome transcriptomic responses in patients undergoing psychostimulant methamphetamine withdrawal.

Methamphetamine (METH) addiction and withdrawal cause serious harm to both the immune system and nervous system. However, the pathogenesis remains largely unknown. Herein, we investigated the peripheral cytokines and exosomal transcriptome regulatory networks in the patients with METH use disorders (MUDs) undergoing withdrawal. Twenty-seven cytokines were simultaneously assessed in 51 subjects, including 22 at the acute withdrawal (AW) stage and 29 at the protracted withdrawal (PW) stage, and 31 age and gender-matched healthy controls (HCs). Compared to the HCs, significantly decreased levels of interleukin (IL)-1ß, IL-9, IL-15, Basic FGF, and MIP1a, increased levels of IL-1rα, IL-6, Eotaxin IP-10, VEGF, and RANTES were identified in AW. These disturbances were mostly or partly restored to the baseline in PW. However, the cytokines IL-6, IL-7, and IL-12p70 were consistently increased even after one year of withdrawal. Besides, a significant decrease in CD3+T and CD4+T cell numbers was observed in AW, and the diminishment was restored to baseline in PW. Comparatively, there were no statistically significant changes in CD8+T, NK, and B cells. Furthermore, the exosomal mRNAs and long non-coding RNAs (lncRNA) were profiled, and the lncRNA-miRNA-mRNA networks were constructed and associated with METH AW and PW stages. Notably, the chemokine signaling was remarkably upregulated during AW. By contrast, the differentially expressed mRNAs/lincRNAs were significantly enriched in neurodegeneration-related diseases. Taken together, a group of METH withdrawal-related cytokines and exosomal mRNA/lncRNA regulatory networks were obtained, which provides a useful experimental and theoretical basis for further understanding of the pathogenesis of the withdrawal symptoms in MUDs.

Transformation of food waste to source of antimicrobial proteins by black soldier fly larvae for defense against marine Vibrio parahaemolyticus.

Insect biorefinery by black soldier fly larvae (BSFL), Hermetia illucens, has emerged as an innovative technique for the valorization of food waste. However, despite BSFL being an attractive natural source of antimicrobial proteins (AMPs), there is a scarcity of research on the antimicrobial activity and transcriptome expression of AMPs derived from BSFL following waste treatment. In the present study, food waste treatment was performed by BSFL with a substrate C/N ratio ranging from 21:1 to 10:1, marine Vibrio parahaemolyticus (VP) was selected as the model aquaculture pathogen, the antimicrobial activities of AMPs in vitro and zebrafish in vivo were examined, and the molecular mechanism of the C/N-dependent AMP difference was expounded. Findings were made that the AMP extract of C/N16:1 resulted in relatively higher antimicrobial activity in vitro than that of other C/Ns. Further, the AMPs of C/N16:1 exhibited a promising in vivo defense effect for elevating the 96-h survival rate of zebrafish from 0% to 39% after VP infection, comparable to the animal antibiotic sulfamethoxidine. The results of transcriptome analysis reveal that lysozymes were the highest expressed components in the AMP gene family. The C/N16:1 BSFL significantly up-regulated 12 out of 51 lysozyme genes compared with C/N21:1, which likely contributed to the improvement of AMP antimicrobial activity. Further, C/N16:1 significantly up-regulated the expression of lysozyme, glycosyl hydrolase and muscle protein genes compared with C/N21:1, which likely enhanced the defense ability of the immune system, the utilization of the starch-like substrate, and the mobility of the larvae, thereby facilitating the larval transformation and AMP production. Overall, such results indicate that waste C/N ratio interacted with the activity and expression of BSFL AMPs through transcriptome regulation, and the BSFL AMPs derived from food waste could be used for the defense against marine pathogens to support the sustainable development of aquaculture.

Metformin modulates microbiota-derived inosine and ameliorates methamphetamine-induced anxiety and depression-like withdrawal symptoms in mice.

BACKGROUND: Metformin exhibits therapeutic potential in behavioural deficits induced by methamphetamine (METH) in rats. Emerging studies suggest gut microbiota may impact psychiatric symptoms, but there is no direct evidence supporting metformin's participation in the pathophysiology of withdrawal symptoms via modulation of gut microbiota. METHODS: In order to define the functional impacts of gut microbiota and metformin to the behavioural deficits during METH withdrawal, we utilized a combination of fecal microbiota transplantation (FMT), high-throughput sequencing, and untargeted metabolomics technologies. RESULTS: First, METH addicts exhibited higher α diversity and distinct microbial structures compared to healthy controls. In particular, the relative abundance of Rikenellaceae was positively correlated with the severity of anxiety and depression. Second, both human-to-mouse and mouse-to-mouse FMTs confirmed that METH-altered-microbiota transplantation is sufficient to promote anxiety and depression-like behaviours in recipient germ-free mice, and these behavioural disturbances could be ameliorated by metformin. In-depth analysis revealed that METH significantly altered the bacterial composition and structure as well as relative abundance of several bacterial taxa and metabolites, including Rikenellaceae and inosine, respectively, whereas add-on metformin could remodel these alterations. Finally, the inosine complementation successfully restored METH-induced anxiety and depression-like behaviours in mice. CONCLUSION: This study demonstrates that METH withdrawal-induced anxiety and depression-like behaviours are reversible and transmissible via gut microbiota in a mouse model. The therapeutic effects of metformin on psychiatric manifestations are associated with microbiota-derived metabolites, highlighting the role of the gut microbiota in substance use disorders and the pathophysiology of withdrawal symptoms.

The Association of Altered Gut Microbiota and Intestinal Mucosal Barrier Integrity in Mice With Heroin Dependence.

The gut microbiota is believed to play a significant role in psychological and gastrointestinal symptoms in heroin addicts. However, the underlying mechanism remains largely unknown. We show here that heroin addicts had a decrease in body mass index (BMI) and abnormal serum D-lactic acid (DLA), endotoxin (ET) and diamine oxidase (DAO) levels during their withdrawal stage, suggesting a potential intestinal injury. The gut microbial profiles in the mouse model with heroin dependence showed slightly decreased alpha diversity, as well as higher levels of Bifidobacterium and Sutterella and a decrease in Akkermansia at genus level compared to the control group. Fecal microbiota transplantation (FMT) further confirmed that the microbiota altered by heroin dependence was sufficient to impair body weight and intestinal mucosal barrier integrity in recipient mice. Moreover, short-chain fatty acids (SCFAs) profiling revealed that microbiota-derived propionic acid significantly decreased in heroin dependent mice compared to controls. Overall, our study shows that heroin dependence significantly altered gut microbiota and impaired intestinal mucosal barrier integrity in mice, highlighting the role of the gut microbiota in substance use disorders and the pathophysiology of withdrawal symptoms.

Link between characteristics of Fe(III) oxides and critical role in enhancing anaerobic methanogenic degradation of complex organic compounds.

Fe(III) oxides have been investigated to accelerate anaerobic methanogenic degradation of complex organic compounds. However, the critical role linked to the characteristics of different types of Fe(III) oxides is still unclear. Study presented here performed a side-by-side comparison of four types of Fe(III) oxides including Fe(III)-citrate, ferrihydrite, hematite and magnetite to evaluate their effectiveness in methanogenic degradation of phenol. Results showed that, amorphous Fe(III)-citrate group showed the fastest phenol degradation and Fe2+ release among all the groups, followed by poorly crystalline ferrihydrite. Although Fe(III)-citrate group also showed the fastest methane production rate, the efficiency of electron recovery in methane production was only 58-78%, which was evidently lower than that in both crystalline hematite (86-89%) and magnetite (93-97%) groups. Methane production rate with non-conductive ferrihydrite was nearly same as that with conductive magnetite, both of which were significantly higher than that with semi-conductive hematite. X-ray Diffraction (XRD) and X-ray photoelectron spectroscopy (XPS) analysis showed that sludge collected from hematite and magnetite group still respectively presented a relatively intact characteristic spectra involved in hematite and magnetite. Differently, the characteristic spectra involved in ferrihydrite was not evident in sludge collected from ferrihydrite group, whereas the characteristic spectra involved in magnetite was detected. Microbial community analysis showed that, both Fe(III)-citrate and ferrihydrite specially enriched Fe(III)-reducing bacteria capable of degrading phenol into fatty acids (Trichococcus and Caloramator) via dissimilatory Fe(III) reduction. Fe(III)-citrate also stimulated the growth of Syntrophus capable of degrading phenol/benzoate into acetate and proceeding direct interspecies electron transfer (DIET). In magnetite and hematite group, the abundance of Enterococcus species evidently increased, and they might proceed DIET with Methanothrix species in syntrophic conversion of fatty acids into methane.

High-efficiency methanogenesis via kitchen wastes served as ethanol source to establish direct interspecies electron transfer during anaerobic Co-digestion with waste activated sludge.

Kitchen wastes (KW) have been widely investigated for bio-ethanol production, while no study utilizes KW as ethanol source to stimulate the methanogenic communities to perform direct interspecies electron transfer (DIET), since the excess acidity contained after the biological ethanol-type fermentation pretreatment (BEFP) can seriously inhibit the DIET-based syntrophic metabolism. In this study, a strategy that utilized waste activated sludge (WAS) as co-substrate to relieve the excess acidity after BEFP during anaerobic co-digestion (AcoD) was proposed. The results showed that, under the mixed ratio of 1:2 and 1:5 (KW:WAS, volume ratio), both methane production and organic compound removal evidently increased, compared with that treating the sole WAS. Conversely, under the other mixed ratios (sole KW, 5:1, 2:1 and 1:1), no methane but the evident hydrogen production was detected, and syntrophic metabolism of organic acids and alcohols was prevented. Three-dimensional excitation emission matrix (3D-EEM) analysis showed that the protein-like organic compounds contained in both KW and WAS were effectively degraded. Furthermore, the maximum methane production potential from WAS during AcoD (260.5 ± 4.1 and 264.3 ± 2.7 mL/g-COD) was higher than that treating sole WAS (250.8 ± 0.1 mL/g-COD). Microbial community analysis showed that, some genera capable of metabolizing the complex organic compounds with the reduction of the elemental sulfur or equipped with the electrically conductive pili were specially enriched during AcoD under the mixed ratio of 1:2 and 1:5. They might proceed DIET with methanogens, such as Methanosarcina and Methanospirillum species, to maintain the syntrophic metabolism effective and stable, since the abundance of both Methanosarcina and Methanospirillum species evidently increased.

A comparison study on the clinical effects of foscarnet sodium injection and interferon on human immunodeficiency virus-infected patients complicated with herpes zoster.

OBJECTIVE: To compare the clinical effects of foscarnet sodium injection and interferon on human immunodeficiency virus (HIV)-infected patients complicated with herpes zoster. METHODS: Ninety HIV-infected patients complicated with herpes zoster were divided into a treatment group and a control group that were both treated routinely first. Then the control group and treatment group were administered with interferon and foscarnet sodium injection respectively for four consecutive weeks. RESULTS: After four weeks, the effective rates of the treatment and control groups were 95.6% and 80.0% respectively, which were significantly different (P < 0.05). The pain scores of the two groups were similar before treatment, but the scores of the treatment group were significantly lower than those of the control group two and four weeks after treatment (P < 0.05) as well as were significantly lower than those before treatment (P < 0.05). The numbers of CD4+ cells and the contents of IL-2 of both groups two and four weeks after treatment significantly exceeded those before treatment (P < 0.05), with significant inter-group differences also (P < 0.05). Two and four weeks after treatment, the treatment group scored significantly higher in physical activity, energy, sleep, social life and emotional reaction than the control group did (P < 0.05). CONCLUSIONS: HIV-infected patients are prone to being complicated with herpes zoster. Compared with interferon, foscarnet sodium injection better improves the clinical outcomes by effectively relieving pain and by regulating immune mediated inflammatory diseases, thus boosting the prognostic quality of life.