Retrorectal mucinous adenocarcinoma arising from a tailgut cyst: A case report and review of literature.

BACKGROUND: Tailgut cysts are defined as congenital cysts that develop in the rectosacral space from the residue of the primitive tail. As a congenital disease, caudal cysts are very rare, and their canceration is even rarer, which makes the disease prone to misdiagnosis and delayed treatment. We describe a case of caudal cyst with adenocarcinogenesis and summarize in detail the characteristics of cases with analytical value reported since 1990. CASE SUMMARY: A 35-year-old woman found a mass in her lower abdomen 2 mo ago. She was asymptomatic at that time and was not treated because of the coronavirus disease 2019 pandemic. Two weeks ago, the patient developed abdominal distension and right waist discomfort and came to our hospital. Except for the high level of serum carcinoembryonic antigen, the medical history and laboratory tests were not remarkable. Magnetic resonance imaging showed a well-defined, slightly lobulated cystic-solid mass with a straight diameter of approximately 10 cm × 9 cm in the presacral space, slightly high signal intensity on T2-weighted imaging, and moderate signal intensity on T1-weighted imaging. The mass was completely removed by laparoscopic surgery. Histopathological examination showed that the lesion was an intestinal mucinous adenocarcinoma, and the multidisciplinary team decided to implement postoperative chemotherapy. The patient recovered well, the tumor marker levels returned to normal, and tumor-free survival has been achieved thus far. CONCLUSION: The case and literature summary can help clinicians and researchers develop appropriate examination and therapeutic methods for diagnosis and treatment of this rare disease.

Cyanidin-3-O-glucoside extracted from the Chinese bayberry (Myrica rubra Sieb. et Zucc.) alleviates antibiotic-associated diarrhea by regulating gut microbiota and down-regulating inflammatory factors in NF-κB pathway.

Chinese bayberry has been used to treat diarrhea in China for more than 2,000 years, but the mechanism is not clear. Due to the extensive use of antibiotics, antibiotic-associated diarrhea (AAD) is becoming more and more common in clinic, but there is no effective drug for the treatment. The present study aimed to explore the therapeutic effect of Chinese bayberry on AAD for the first time, and explained the underlying mechanism from different aspects. The BALB/c mice model was established by intragastric administration of lincomycin (3 g/kg). Successfully modeled mice were treated with purified water, dried bayberry powder suspension (100 mg/kg), C3G suspension (40 mg/kg) and montmorillonite powder suspension (40 mg/kg), respectively. The changes of body weight, diarrhea index, diarrhea status score were recorded and calculated regularly. 16S rRNA gene sequencing, intestinal immunofluorescence and inflammatory factor detection were further performed. The treatment with dried bayberry powder suspension and C3G suspension could rapidly reduce the diarrhea score and diarrhea index, increase food intake and restore body weight gain. The gut microbiota richness and diversity were significantly increased after dried bayberry powder suspension and C3G suspension treatments, typically decreased bacterial genera Enterococcus and Clostridium senus stricto 1. In addition, intake of Chinese bayberry powder and C3G significantly decreased the level of p65 phosphorylation, and up-regulated the expression of intestinal tight junction protein claudin-1 and ZO-1. Chinese bayberry fruit had the effect of alleviating AAD, and C3G was supposed to play the predominant role. The mechanism was indicated to be related with restoring the homeostasis of gut microbiota, inhibiting the level of harmful bacteria and increasing the abundance of beneficial bacteria, down-regulating TNF-α, IL-6, and IL-12 factors to reduce inflammation, restoring intestinal tight junction proteins and reducing intestinal permeability.

CO-Releasing Molecule (CORM)-3 Ameliorates Spinal Cord-Blood Barrier Disruption Following Injury to the Spinal Cord.

Spinal cord injury (SCI) is a clinical tough neurological problem without efficient cure currently. Blood-spinal cord barrier (BSCB) interruption is not only a crucial pathological feature for SCI process but is a possible target for future SCI treatments; however, few treatments have been developed to intervene BSCB. In the present study, we intravenously injected CO-releasing molecule3 (CORM-3), a classical exogenous CO donor, to the rats experiencing SCI and assessed its protection on BSCB integrity in rats. Our results demonstrated that the exogenous increasing of CO by CORM-3 blocked the tight junction (TJ) protein degeneration and neutrophils infiltration, subsequently suppressed the BSCB damage and improved the motor recovery after SCI. And we certified that the CO-induced down-regulation of MMP-9 expression and activity in neutrophil might be associated with the NF-κB signaling. Taken together, our study indicates that CO-releasing molecule (CORM)-3 ameliorates BSCB after spinal cord injury.

Carbon monoxide releasing molecule-3 alleviates neuron death after spinal cord injury via inflammasome regulation.

BACKGROUND: Genetic overexpression or pharmacological activation of heme oxygenase (HO) are identified as potential therapeutic target for spinal cord injury (SCI); however, the role of carbon monoxide (CO), which is a major product of haem degenerated by HO, in SCI remains unknown. Applying hemin or chemicals which may regulate HO expression or activity to increase CO production are inadequate to elaborate the direct role of CO. Here, we assessed the effect of CO releasing molecule-3 (CORM-3), the classical donor of CO, in SCI and explained its possible protective mechanism. METHODS: Rat SCI model was performed with a vascular clip (30 g) compressing at T9 vertebral level for 1 min and CO was delivered immediately after SCI by CORM-3. The neurological deficits and neuron survival were assessed. Inflammasome and inositol-requiring enzyme 1 (IRE1) pathway were measured by western blot and immunofluorescence. For in vitro study, oxygen glucose deprivation (OGD) simulated the SCI-inflammasome change in cultured the primary neurons. FINDINGS: CORM-3 suppressed inflammasome signaling and pyroptosis occurrence, which consequently alleviated neuron death and improved motor functional recovery following SCI. As a pivotal sensor involving in endoplasmic reticulum stress-medicated inflammasome signaling, IRE1 and its downstream X-box binding protein 1 (XBP1) were activated in SCI tissues as well as in OGD neurons; while inhibition of IRE1 by STF-083010 in SCI rats or by si-RNA in OGD neurons suppressed inflammasome signaling and pyroptosis. Interestingly, the SCI/OGD-stimulated IRE1 activation was attenuated by CORM-3 treatment. INTERPRETATIONS: CO may alleviate neuron death and improve motor functional recovery in SCI through IRE1 regulation, and administration of CO could be a promising therapeutic strategy for SCI.

TFEB protects nucleus pulposus cells against apoptosis and senescence via restoring autophagic flux.

OBJECTIVE: Excessive apoptosis and senescence of nucleus pulposus (NP) cells are major pathological changes in intervertebral disc degeneration (IVDD) development; previous studies demonstrated pharmacologically or genetically stimulation of autophagy may inhibit apoptosis and senescence in NP cells. Transcription factor EB (TFEB) is a master regulator of autophagic flux via initiating autophagy-related genes and lysosomal biogenesis. This study was performed to confirm whether TFEB was involved in IVDD development and its mechanism. METHODS: TFEB activity was detected in NP tissues in puncture-induced rat IVDD model by immunofluorescence as well as in tert-Butyl hydroperoxide (TBHP), the reactive oxygen species (ROS) donor to induce oxidative stress, treated NP cells by western blot. After TFEB overexpression in NP cells with lentivirus transfection, autophagic flux, apoptosis and senescence percentage were assessed. In in vivo study, the lentivirus-normal control (LV-NC) or lentivirus-TFEB (LV-TFEB) were injected into the center space of the NP tissue, after 4 or 8 weeks, Magnetic resonance imaging (MRI), X ray, Hematoxylin-Eosin (HE) and Safranin O staining were used to evaluate IVDD grades. RESULTS: The nuclear localization of TFEB declined in degenerated rat NP tissue as well as in TBHP treated NP cells. Applying lentivirus to transfect NP cells, TFEB overexpression restored the TBHP-induced autophagic flux blockage and protected NP cells against apoptosis and senescence; these protections of TFEB are diminished by chloroquine-medicated autophagy inhibition. Furthermore, TFEB overexpression ameliorates the puncture-induced IVDD development in rats. CONCLUSIONS: Experimental IVDD inhibited the TFEB activity. TFEB overexpression suppressed TBHP-induced apoptosis and senescence via autophagic flux stimulation in NP cell and alleviates puncture-induced IVDD development in vivo.

TFEB, a potential therapeutic target for osteoarthritis via autophagy regulation.

The blockage of autophagic flux in chondrocytes has been considered as a major reason for the excessive cellular apoptosis and senescence in osteoarthritis (OA) development; however, the molecular mechanism and therapeutic strategy for interrupted autophagic flux is still not clear. Most recently, the transcription factor EB (TFEB) is identified as a master regulator for autophagic flux via initiating the expression of multiple autophagy-related genes and lysosomal biogenesis. This research was performed to confirm whether TFEB expression and activity are impacted in OA development and to confirm the effect of genetic up-regulation of TFEB on autophagic flux and cellular protection in the in vitro and in vivo models of OA. We demonstrated that the expression and nuclear localization of TFEB is decreased in human and mouse OA cartilage as well as in tert-Butyl hydroperoxide (TBHP)-treated chondrocytes. Applying lentivirus to transfect chondrocytes, we found that TFEB overexpression rescues the TBHP-induced the autophagic flux damage, lysosome dysfunction and protects chondrocyte against TBHP induced apoptosis and senescence; these protections of TFEB are diminished by chloroquine-medicated autophagy inhibition. Our destabilized medial meniscus (DMM) mouse OA model shows that TFEB overexpression ameliorates the surgery-induced cartilage degradation, restrains the apoptosis and senescence of chondrocyte, and enhances the autophagic flux. In summary, our study indicates that the activity of TFEB in chondrocyte is involved in OA development, also TFEB overexpression may be a promising strategy for OA treatment.

Monascin inhibits IL-1ß induced catabolism in mouse chondrocytes and ameliorates murine osteoarthritis.

Osteoarthritis (OA) is an age-related degenerative disease and is the fourth major cause of disability, but there are no effective therapies because of its complex pathology and the side effects of the drugs. Previous research demonstrated that inflammation and ECM degradation play major roles in OA development. Monascin is an azaphilonoid pigment extracted from Monascus-fermented rice with a potential anti-inflammatory effect reported in various preclinical studies. In the present study, we investigated the protectiveness of monascin on interleukin (IL)-1ß-induced mouse chondrocytes and surgical destabilization of the medial meniscus mouse (DMM) OA models. In vitro, monascin treatment inhibited the IL-1ß-induced expression of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor alpha (TNF-α), and interleukin-6 (IL-6). In addition, the IL-1ß-stimulated matrix metalloproteinase-13 (MMP-13) and thrombospondin motifs 5 (ADAMTS-5) upregulation and type two collagen and aggrecan degradation were reversed by monascin. Mechanistically, we revealed that monascin suppressed nuclear factor kappa B (NF-κB) signalling by activating the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in IL-1ß-induced chondrocytes. And monascin-induced protectiveness in OA development was also shown by using a DMM model. Altogether, our results suggested that monascin could be a novel therapeutic approach for OA.