Rejected

Asperuloside (ASP) and geniposide (GP) are iridoids that have shown various biological properties, such as reduction of inflammation, oxidative stress, and neuroprotection. The aim of this study was to investigate the mechanism of action of ASP and GP through the experimental model of pilocarpine-induced seizures. Mice were treated daily with saline, valproic acid (VPA), GP (5, 25, or 50 mg/kg), or ASP (20 or 40 mg/kg) for 8 days. Pilocarpine (PILO) treatment was administered after the last day of treatment, and the epileptic behavior was recorded for 1 h and analyzed by an adapted scale. Afterward, the hippocampus and blood samples were collected for western blot analyses, ELISA and comet assay, and bone marrow to the micronucleus test. We evaluated the expression of the inflammatory marker cyclooxygenase-2 (COX-2), GluN2B, a subunit of the NMDA receptor, pGluR1, an AMPA receptor, and the enzyme GAD-1 by western blot and the cytokine TNF-α by ELISA. The treatments with GP and ASP were capable to decrease the latency to the first seizure, although they did not change the latency to status epilepticus (SE). ASP demonstrated a genotoxic potential analyzed by comet assay; however, the micronuclei frequency was not increased in the bone marrow. The GP and ASP treatments were capable to reduce COX-2 and GluN2B receptor expression after PILO exposure. This study suggests that GP and ASP have a protective effect on PILO-induced seizures, decreasing GluN2B receptor and COX-2 expression.

Recently, cryotherapy has become a common practice for postoperative pain management. The current accepted practice in Japan is the use of cryotherapy at 5 °C after arthroscopic shoulder surgery. However, this therapy has been reported to be highly intense because the sustained low temperature causes discomfort for patients. The optimum temperature and duration of cooling required for comfortable and effective cryotherapy after arthroscopic shoulder surgery were investigated.

Mirogabalin, a selective voltage-gated calcium channel α2δ ligand, improves peripheral neuropathic pain; however, its effects on patients with cancers including pancreatic ductal adenocarcinoma (PDAC) remain unknown. We analyzed the effects of mirogabalin on a KPPC (LSL-KrasG12D/+; Trp53flox/flox; Pdx-1cre/+) mouse model of PDAC. Six-week-old KPPC mice received oral mirogabalin (10 mg/kg/day) (n = 10) or vehicle water (n = 14) until the humane end point. Cancer-associated pain was evaluated using the scores of hunching and mouse grimace scale (MGS). Tumor status and plasma cytokine levels were determined using histopathological analysis and cytokine array, respectively. The effects of mirogabalin on the proliferative ability of PDAC cell lines were determined. The scores of the hunching and MGS improved after mirogabalin administration with a decrease in the plasma levels of inflammatory cytokines, such as tumor necrosis factor-α, interleukin-6, and interferon-γ. Although no significant difference in the survival rate was observed, mirogabalin significantly increased pancreatic tumor size and proliferative index of Ki-67 and cyclins. Local arginase-1+ M2-like tumor-associated macrophages and CD31+ tumor blood vessels increased after mirogabalin administration. By contrast, the number of α-smooth muscle actin+ cancer-associated fibroblasts, desmoplastic stroma, and CD8+ T cells decreased. Local myeloperoxidase+ tumor-associated neutrophils and CD45R+ B cells were unaltered. Mirogabalin enhanced the proliferative ability of PDAC cell lines with the upregulation of cyclins and cyclin-dependent kinases; however, it inhibited the potential of pancreatic stellate cells in vitro. Therefore, our results suggest that mirogabalin improves cancer-associated pain but enhances the proliferative potential of PDAC in vitro and in vivo.

Synovial inflammation plays a central role in joint destruction and pain in osteoarthritis (OA). The NF-κB pathway plays an important role in the inflammatory process and is activated in OA. A previous study reported that a jietacin derivative (JD), ()-2-(8-oxodec-9-yn-1-yl)-1-vinyldiazene 1-oxide, suppressed the nuclear translocation of NF-κB in a range of cancer cell lines. However, the effect of JD in synovial cells and the exact mechanism of JD as an NF-κB inhibitor remain to be determined. We investigated the effect of JD on TNF-α-induced inflammatory reaction in a synovial cell line, SW982 and human primary synovial fibroblasts (hPSFs). Additionally, we examined phosphorylated levels of p65 and p38 and expression of importin α3 and β1 using Western blotting. RNA-Seq analysis revealed that JD suppressed TNF-α-induced differential expression: among 204 genes significantly differentially expressed between vehicle and TNF-α-stimulated SW982 (183 upregulated and 21 downregulated) (FC ≥ 2, Q < 0.05), expression of 130 upregulated genes, including inflammatory cytokines (, , , ) and chemokines (, , , , , 10, 11), was decreased by JD treatment and that of 14 downregulated genes was increased. KEGG pathway analysis showed that DEGs were increased in the cytokine-cytokine receptor interaction, TNF signaling pathway, NF-κB signaling pathway, and rheumatoid arthritis. JD inhibited , and mRNA expression and IL-6 and IL-8 protein production in both SW982 and hPSFs. JD also suppressed p65 phosphorylation in both SW982 and hPSFs. In contrast, JD did not alter p38 phosphorylation. JD may inhibit TNF-α-mediated inflammatory cytokine production via suppression of p65 phosphorylation in both SW982 and hPSFs. Our results suggest that JD may have therapeutic potential for OA due to its anti-inflammatory action through selective suppression of the NF-κB pathway on synovial cells.

(Lour.) C. B. Robinson, belonging to the family Lauraceae, is a multipurpose and fast-growing evergreen or deciduous tree that has been traditionally used for numerous purposes such as treatment for diarrhea, dysentery, abdominal pain, indigestion, gastroenteritis, edema, traumatic injuries, colds, arthritis, asthma, diabetes, pain relief, and poignant sexual power. This study aimed to summarize the chemical reports, folk values, and phytopharmacological activities of , based on available information screened from diverse databases. An up-to-date electronic-based search was accomplished to obtain detailed information, with the help of several databases such as Google Scholar, Scopus, SpringerLink, Web of Science, ScienceDirect, ResearchGate, PubMed, ChemSpider, Elsevier, BioMed Central, and the USPTO, CIPO, INPI, Google Patents, and Espacenet, using relevant keywords. Outcomes advocate that, up to the present time, alkaloids, glycosides, and terpenoids are abundant in, and the most bioactive constituents of, this natural plant. Results demonstrated that has various remarkable biological activities, including antioxidant, anti-inflammatory, anti-microbial, anticancer, antipyretic, anti-diabetic, analgesic, hepatoprotective, and wound-healing activity. One study revealed that exhibited significant aphrodisiac and anti-infertility activity. Nevertheless, no clinical studies have been cited. Taken together, may be one of the significant sources of bioactive constituents that could potentially lead to different effective pharmacological activities. On the other hand, future research should focus on clinical studies and several toxicity evaluations, such as sub-chronic toxicity, teratogenicity, and genotoxicity.

To summarize the clinical characteristics and treatment effect of patients with acute oral 84 disinfectant poisoning, so as to improve the understanding, diagnosis and treatment of the disease. In January 2022, 25 hospitalized patients with acute oral 84 disinfectant poisoning admitted to our department from March 2016 to August 2021 were selected as the research objects, and their general conditions, poisoning reasons, poisoning time, dose of poisoning, clinical manifestations, blood routine and biochemical indicators, diagnosis, treatment and prognosis were selected. A retrospective analysis was performed. Among the 25 patients, there were 4 males and 21 females, aged from 20 to 91 years, and ((1), (3)) was 38.7 (27, 46) years; The poisoning time (from exposure to poison to treatment) was 1~72 h, and ((1), (3)) was 10.5 (3, 11.5) h. The length of stay was 1~20 days, and ((1), (3)) was 5.72 (2, 7) days.The dose was 40-500 ml, and the ((1), (3)) was 219.6 (100, 330) ml. Chest CT showed exudative changes in both lungs in 4 patients, excessive decreased permeability in 1 case and pleural effusion in 1 case. Gastroscope showed 2 cases of erosive inflammation of gastric body and antrum, 1 case of esophageal ulcer and cardiac ulcer, 1 case of corrosive gastritis, gastric fundus ulcer and esophageal stenosis. Abdominal X-ray showed 1 case of abdominal intestinal dilatation and pneumatosis with multiple gas-liquid planes.There were 1 case of type I respiratory failure, 6 cases of gastrointestinal bleeding and 1 case of incomplete intestinal obstruction. There were 19 cases of nausea and vomiting, 9 cases of abdominal pain, 6 cases of pharyngeal pain and 6 cases of retrosternal burning pain, 1 case of cough and 2 cases of fatigue. Acute oral 84 disinfectant will cause varying degrees of damage to the human digestive tract and lungs. In severe cases, gastrointestinal bleeding, intestinal obstruction, hypoxemia, etc, and even life-threatening, should be paid attention to clinically. The treatment is mainly symptomatic support treatment, such as protecting gastrointestinal mucosa, controlling acute inflammatory reaction, protecting the functions of liver and kidney and other important organs.

Acne vulgaris is a well-recognized condition among adolescents and adults that adversely affects their quality of life. Local cryotherapy has long been reported to be effective in treating acne vulgaris, inducing a more rapid involution of acne than topical medications. However, the use of cryotherapy has been limited for acne treatment due to several drawbacks, including procedural pain and pigmentary alterations. Currently, newer cryotherapy devices are gaining attention in dermatology due to their ability to monitor and precisely control the target temperature. In this narrative review, a brief history and the latest update on acne cryotherapy will be presented. Additionally, a special emphasis is placed on the role of cryotherapy, alone or in combination with intralesional steroid injections for nodulocystic acne.

The purpose of this study is to determine the possible alterations that may occur in the thickness of the retinal nerve fibre layer (RNFL), ganglion cell layer (GCL), and macular thickness in patients with chronic migraines compared with healthy controls. Hence, we examined some of the possibilities that are offered by optical coherence tomography (OCT) in order to study different neurological diseases and to study its application, in this case, how it may be applied to patients with chronic migraines. This was an observational cross-sectional study in adults aged 18-65 years. The study group consisted of 90 patients (90 eyes) with chronic migraines who met the inclusion criteria, and 90 healthy controls (90 eyes) matched for age and sex. Retinal thickness was measured by spectral domain OCT (SD-OCT). The thickness of the superior quadrant of the peripapillary RNFL, as well as the mean thickness in the macula, RNFL macular, and GCL was significantly thinner in chronic migraine patients than in healthy controls ( ≤ 0.05). Chronic migraines are associated with a decrease in retinal thickness which is detectable by an OCT diagnostic technique. The quantification of the axonal damage could be used as a biomarker to help in the diagnosis and monitoring of this pathology. Further studies will be needed to confirm these findings.

Andrographolide (Andro), the major constituent of , is was known to reduces inflammatory reaction. In the current study, the ability of Andro to reduce pain sensation in a rat post-operative wound model was explored. The hind paws of 18 Sprague-Dawley rats (SD) bearing post-operative wounds received the following three treatments: Saline, Andro via direct injection into the paw (Andro-injected) and Tablet containing Andro + poly (lactic-co-glycolic acid) (PLGA) (Andro-tablet). Von Frey tests assessed mechanical allodynia at 1, 3, 5 h and 1-, 2-, 3-, 4-, and 5-days post-operation. Behavioral analyses were performed to measure reaction threshold and reaction frequencies. Immunoreactivity of p-ERK and GluR1 was examined in the dorsal horn of the spinal cord. Histopathological and immunostaining studies were conducted on paw epidermis to observe the gross morphology and angiogenesis. The threshold for inducing allodynia increased and the reaction frequency reduced in the Andro-injected group compared to the saline-group, at 3 h post-surgery and the effect lasted between 3-4 days. The threshold for inducing pain and reaction frequency for the Andro-tablet group did not differ from the saline-treated group. The levels of p-ERK and GluR1 in the dorsal horn were reduced after Andro treatment. No significant difference in wound healing index was observed between saline and Andro-injected groups, but CD-31 staining showed less angiogenesis in the Andro-injected group. Andro significantly reduced mechanical allodynia compared to saline treatment, both in shorter and longer time frames. Furthermore, Andro influenced the expression of p-ERK and GluR1 in the dorsal horn, and the angiogenesis process in the wound healing area.

genus is widely used in traditional treatment against fever, headache, hepatobiliary disorders, skin ulcers, diabetes, and rheumatism, as well as an antispasmodic and diuretic. Its phytochemistry mainly shows the presence of flavonoids and terpenoids such as monoterpenes, sesquiterpenes, diterpenes, and triterpenes. Some of them have been evaluated for biological activities presenting allelopathic, antimicrobial, cytotoxic, and anti-inflammatory properties. In this paper, our research group reported the isolation, characterization, and antifungal evaluation of several molecules isolated from the dichloromethane extract from , , and against the phytopathogen fungus . The isolated compounds have not previously been tested against , revealing an important source of antifungals in the genus . Six known flavones were isolated from . The dichloromethane extracts of and were subjected to a bio-guided isolation, obtaining three known flavones, an α-hydroxidihydrochalcone mixture, one labdane, one triterpene, and two norbisabolenes from the most active fractions. The compounds 4'-methoxy-α-hydroxydihydrochalcone (), 3β,15-dihydroxylabdan-7-en-17-al (), and 13-nor-11,12-dihydroxybisabol-2-enone () are novel. The most active compounds were the Salvigenin () and 1,2-dihydrosenedigital-2-one () with an IC50 of 13.5 and 3.1 μg/mL, respectively.