Arthrospira Enhances Seroclearance in Patients with Chronic Hepatitis B Receiving Nucleos(t)ide Analogue through Modulation of TNF-α/IFN-γ Profile.

Chronic hepatitis B (CHB) virus infection, causing immune dysfunction and chronic hepatitis, is one of the leading risk factors for hepatocellular cancer. We investigated how Arthrospira affected hepatitis B surface antigen (HBsAg) reduction in CHB patients under continued nucleos(t)ide analogues (NA). Sixty CHB patients who had been receiving NA for at least one year with undetectable HBV DNA were randomized into three groups: control and oral Arthrospira at 3 or 6 g daily add-on therapy groups. Patients were followed up for 6 months. Oral Arthrospira-diet mice were established to investigate the possible immunological mechanism of Arthrospira against HBV. Within 6 months, mean quantitative HBsAg (qHBsAg) decreased in the oral Arthrospira add-on therapy group. Interestingly, interferon gamma (IFN-γ) increased but TNF-α, interleukin 6 (IL-6), hepatic fibrosis, and steatosis decreased in the add-on groups. In mice, Arthrospira enhanced both innate and adaptive immune system, especially natural killer (NK) cell cytotoxicity, B cell activation, and the interleukin 2 (IL-2), IFN-γ immune response. Arthrospira may modulate IL-2- and TNF-α/IFN-γ-mediated B and T cell activation to reduce HBsAg. Also, Arthrospira has the potential to restore immune tolerance and enhance HBsAg seroclearance in CHB patients through promoting T, B, and NK cell activation.

Percutaneous endoscopic gastrostomy prior to esophagectomy for esophageal cancer - a systematic review and meta-analysis.

BACKGROUND: For resectable esophageal cancer (EC), it remains controversial whether to place percutaneous endoscopic gastrostomy (PEG) before the curative surgery to provide nutritional support during the neoadjuvant therapy. OBJECTIVE: To compare surgical outcomes for patients who received preoperative PEG and those without PEG placement (No-PEG) insertion prior to surgery in a potentially operable EC. METHODS: A comprehensive literature search was conducted to identify randomized and non-randomized studies comparing PEG and No-PEG groups. RESULTS: Four retrospective studies with a total number of 1,027 patients were identified and included in this meta-analysis. The differences in anastomotic leakage, anastomotic stricture, morbidity, pulmonary complications, wound infection, and hospital stay were not statistically significant between the two groups. Operation time was significantly shorter in the PEG group. There was no PEG-related gastric conduit failure and no leak from the PEG site in the PEG group. CONCLUSION: We conclude preoperative PEG for resectable EC is a safe procedure with no adverse effect on the gastric tube construction and anastomosis, it can be selectively inserted for EC patients with marked weight loss and malnutrition or those at risk of developing malnutrition during neoadjuvant therapy.

Locally Applied Stem Cell Exosome-Scaffold Attenuates Nerve Injury-Induced Pain in Rats.

PURPOSE: Nerve injury-induced pain is difficult to treat. In this study, we developed an alginate scaffold with human umbilical cord mesenchymal stem cell exosomes (EX-SC) to treat nerve injury-induced pain. MATERIALS AND METHODS: The scaffold was prepared and characterized for its physical traits and biocompatibility. In vitro studies of PC12 and HEK293 cells were used to evaluate the neuroprotective and neurotrophic effects of exosomes. Right L5/6 spinal nerve ligation (SNL) was performed in Sprague-Dawley rats to induce mechanical allodynia and thermal hyperalgesia, evaluated by von Frey hair and radiant heat tests. The EX-SC was wrapped around ligated L5/6 spinal nerves for treatment. Western blotting and immunofluorescence staining were used to evaluate neuron/glial activation, cytokines and neurotrophic factor of affected dorsal root ganglion (DRG). RESULTS: In cell culture assay, the exosomes induce neurite outgrowth of PC12 cells and protect PC12 and HEK293 cells against formaldehyde acid treatment. On post-ligation day 21, rats receiving EX-SC had significantly higher median (interquartile range) withdrawal threshold and latency [14.1 (13.7-15.5) g, 14.2 (13.7-15.3) s] than saline-SC-treated rats [2.1 (1.7-3.0) g, 2.0 (1.8-2.4) s, P=0.02 and 0.002]. The EX-SC also attenuated SNL-induced up-regulation of c-Fos, GFAP, Iba1, TNF-α and IL-1ß, while enhancing the level of IL-10 and GDNF, in the ipsilateral L5/6 DRG. After implantation for 21 days, the EX-SC enhanced the expression of myelin basic protein and IL-10 in injured L5/6 axons. CONCLUSION: We demonstrate the EX-SC possesses antinociceptive, anti-inflammation and pro-neurotrophic effects in the SNL pain model. It could be a promising therapeutic alternative for nerve injury-induced pain.

Mesenchymal stem cell exosomes as a cell-free therapy for nerve injury-induced pain in rats.

Nerve injury-induced neuropathic pain is difficult to treat. In this study, we used exosomes derived from human umbilical cord mesenchymal stem cell (UCMSC) as a cell-free therapy for nerve injury-induced pain in rats. Isolated UCMSC exosomes range in size from 30 to 160 nm and contain CD63, HSP60, and CD81 exosome markers. After L5/6 spinal nerve ligation surgery, single intrathecal injection of exosomes reversed nerve ligation-induced mechanical and thermal hypersensitivities of right hindpaw of rats at initial and well-developed pain stages. Moreover, continuous intrathecal infusion of exosomes achieved excellent preventive and reversal effects for nerve ligation-induced pain. In immunofluorescent study, lots of Exo-green-labelled exosomes could be found majorly in the ipsilateral L5 spinal dorsal horn, dorsal root ganglion, and peripheral axons, suggesting the homing ability of UCMSC exosomes. They also appeared in the central terminals or cell bodies of IB4, CGRP, and NF200 sensory neurons. In addition, exosome treatment suppressed nerve ligation-induced upregulation of c-Fos, CNPase, GFAP, and Iba1. All these data suggest that the analgesic effects of exosomes may involve their actions on neuron and glial cells. Exosomes also inhibited the level of TNF-α and IL-1ß, while enhanced the level of IL-10, brain-derived neurotrophic factor, and glial cell line-derived neurotrophic factor in the ipsilateral L5/6 dorsal root ganglion of nerve-ligated rats, indicating anti-inflammatory and proneurotrophic abilities. Protein analysis revealed the content of vascular endothelial growth factor C, angiopoietin-2, and fibroblast growth factor-2 in the exosomes. In summary, intrathecal infusion of exosomes from UCMSCs may be considered as a novel therapeutic approach for nerve injury-induced pain.