BACKGROUND: Tuberculosis spondylitis accounts for approximately 50% of all cases of skeletal tuberculosis. Vitamin D plays a role in the immune system. Vitamin D helps in the activation of TLR-2 and TLR-4, which play a role in the process of tuberculosis infection. The objective of this study was to investigate the effect of oral supplementation with vitamin D on TLR-2 and TLR-4 levels in tuberculosis spondylitis patients.
METHODS: The true Experiment Design Pretest-Posttest with Control Group (Pretest-Posttest with Control Group) was used for this research. TLR-2 and TLR-4 were measured by ELISA. Repeated ANOVA, ANOVA tests, and Kolmogorov-Smirnov normality tests on the SPSS program were used to statistically analyze the results.
RESULTS: In the dose groups of 10,000 IU and 5000 IU, significant increases in the levels of vitamin D, TLR-2, and TLR-4 were observed at weeks 4 and 8 (p < 0.05). In the control group, there was no significant increase.
CONCLUSIONS: Vitamin D supplements can significantly increase TLR-2 and TLR-4 levels. Supplementation with vitamin D 10,000 IU/day for 8 weeks can increase vitamin D levels > 50 ng/dl to optimally act as an immunomodulator.

Aim: To evaluate the use of low-dose naltrexone (LDN) as a broad-spectrum analgesic. Methods: Retrospective cohort study from a single pain management practice using data from 2014 to 2020. Thirty-six patients using LDN for ≥2 months were matched to 42 controls. Pain scores were assessed at initial visit and at most recent/final documented visit using a 10-point scale. Results: Cases reported significantly greater pain reduction (-37.8%) than controls (-4.3%; p < 0.001). Whole sample multivariate modeling predicts 33% pain reduction with LDN, with number needed to treat (for 50% pain reduction) of 3.2. Patients with neuropathic pain appeared to benefit even more than those with \'nociceptive\'/inflammatory pain. Conclusion: LDN is effective in a variety of chronic pain states, likely mediated by TLR-4 antagonism.
Naltrexone has historically been used to treat various substance use disorders, but recent discoveries have sparked interest in using low-dose naltrexone (LDN) to manage chronic pain. This study compared pain levels reported by patients before and after at least 2 months of LDN treatment to those reported by patients with the same painful diseases, who did not take LDN. Overall, patients who took LDN reported significantly more pain relief than patients who did not take LDN. How LDN alleviates pain seems complex, but apparently involves an anti-inflammatory effect on cells in the brain and spinal cord. LDN is extraordinarily safe, with no known risks (unlike most standard pain medications), and should be studied more in the treatment of chronic pain.

The global emergence of the COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has focused the entire world\'s attention toward searching for a potential remedy for this disease. Thus, we investigated the antiviral activity of Agrimonia pilosa ethanol extract (APEE) against SARS-CoV-2 and it exhibited a potent antiviral activity with IC50 of 1.1 ± 0.03 µg/mL. Its mechanism of action was elucidated, and it exhibited a virucidal activity and an inhibition of viral adsorption. Moreover, it presented an immunomodulatory activity as it decreased the upregulation of gene expression of COX-2, iNOS, IL-6, TNF-α, and NF-κB in lipopolysaccharide (LPS)-induced peripheral blood mononuclear cells. A comprehensive analysis of the phytochemical fingerprint of APEE was conducted using LC-ESI-MS/MS technique for the first time. We detected 81 compounds and most of them belong to the flavonoid and coumarin classes. Interestingly, isoflavonoids, procyanidins, and anthocyanins were detected for the first time in A. pilosa. Moreover, the antioxidant activity was evidenced in DPPH (IC50 62.80 µg/mL) and ABTS (201.49 mg Trolox equivalents (TE)/mg) radical scavenging, FRAP (60.84 mg TE/mg), and ORAC (306.54 mg TE/g) assays. Furthermore, the protective effect of APEE was investigated in Lipopolysaccharides (LPS)-induced acute lung injury (ALI) in mice. Lung W/D ratio, serum IL-6, IL-18, IL-1β, HO-1, Caspase-1, caspase-3, TLR-4 expression, TAC, NO, MPO activity, and histopathological examination of lung tissues were assessed. APEE induced a marked downregulation in all inflammation, oxidative stress, apoptosis markers, and TLR-4 expression. In addition, it alleviated all histopathological abnormalities confirming the beneficial effects of APEE in ALI. Therefore, APEE could be a potential source for therapeutic compounds that could be investigated, in future preclinical and clinical trials, in the treatment of patients with COVID-19.

Lipopolysaccharides (LPS) are surface glycoconjugates embedded in the external leaflet of the outer membrane (OM) of the Gram-negative bacteria. They consist of three regions: lipid A, core oligosaccharide (OS), and O-specific polysaccharide or O-antigen. Lipid A is the glycolipid endotoxin domain that anchors the LPS molecule to the OM, and therefore, its chemical structure is crucial in the maintenance of membrane integrity in the Gram-negative bacteria. In this paper, we reported the characterization of the lipid A and OS structures from Pseudoalteromonas nigrifaciens Sq02-Rifr, which is a psychrotrophic Gram-negative bacterium isolated from the intestine of Seriola quinqueradiata. The immunomodulatory activity of both LPS and lipid A was also examined.

Ethion is an organophosphate used commonly in India despite being banned in many other countries. The present study was designed to study the interaction of ethion and lipopolysaccharide (LPS) together on lung after single low dose ethion exposure. Mice (n = 20) were alienated into control and treatment groups (n = 10 each). The treatment group was orally fed ethion (8 mg/kg/animal/day) dissolved in corn oil. The animals (n = 5 each) from both the groups were challenged with 80 μg Escherichia coli lipopolysaccharide (LPS) intranasally and the remaining animals (n = 5 each) were administered normal saline solution after 24 h. Ethion along with LPS induced lung inflammation as indicated by increased neutrophils and total leukocyte count (TLC) in broncheoalveolar lavage fluid. Ethion induced histomorphological alterations in lung as shown by increased pulmonary inflammation score in histopathology. Real time PCR analysis showed that ethion followed by LPS resulted significant (p < 0.05) increase in pulmonary Toll-like receptor (TLR)-4 (48.53 fold), interleukin (IL)-1β (7.05 fold) and tumor necrosis factor (TNF)-α (5.74 fold) mRNA expression. LPS co-exposure suggested synergistic effect on TLR4 and TNF-α mRNA expression. Ethion alone or in combination with LPS resulted genotoxicity in blood cells as detected by comet assay. The data suggested single dietary ethion exposure alone or in conjunction with LPS causes lung inflammation and genotoxicity in blood cells.