In vitro antioxidant capacity of Corryocactus brevistylus (sanky) and its effect on the pancreas morphology of alloxan-induced diabetic rats. / Capacidad antioxidante in vitro del Corryocactus brevistylus (sanky) y su efecto en la morfología del páncreas de ratas diabéticas inducidas con aloxano.

OBJECTIVE.: To determine the in vitro antioxidant capacity of Corryocactus brevistylus and its effect on glycemia and the pancreas of alloxan-induced diabetic rats. MATERIALS AND METHODS.: The antioxidant capacity of the hydroethanolic extract of sanky (HEES) was evaluated by assessing its ability to reduce 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric ion (FRAP). We used thirty adult rats, which were induced to diabetes with two doses of alloxan (80mg/kg). Rats were distributed into 5 groups (n=6), all groups received treatment by orogastric route for eight days. Group I received water, group II received metformin 14mg/kg and groups III, IV and V received sanky juice at 1.0; 4.0 and 16 mL/kg, respectively. Glycemia was evaluated by the rapid method (glucometer) (first and eighth day). After treatment, the animals were sacrificed and the pancreas was removed for histopathological study. RESULTS.: The antioxidant capacity of HEES by DPPH showed an IC50 of 0.77 mg/mL; the FRAP method showed a TEAC-FRAP of 22.31µg/mg. Glycemia decreased on the eighth day of treatment, with respect to the first day; a decrease in glycemia was also found in groups III-V, when compared to group I. Histologically, groups I-II presented severe atrophy and moderate necrosis of the islets of Langerhans; groups IV-V presented hypertrophy and mild multifocal necrosis at the islet level. CONCLUSIONS.: The extract of sanky showed antioxidant capacity in vitro and the juice exerts a hypoglycemic and protective effect on the pancreas.

OBJETIVO.: Determinar la capacidad antioxidante in vitro del Corryocactus brevistylus y su efecto sobre la glicemia y páncreas de ratas diabéticas inducidas con aloxano. MATERIALES Y MÉTODOS.: Se evaluó la capacidad antioxidante del extracto hidroetanólico de sanky (EHES) mediante la capacidad de reducir el 2,2-difenil-1-picrilhidracilo (DPPH) y la capacidad de reducir el ion férrico (FRAP). Se utilizaron 30 ratas adultas inducidas a diabetes con dos dosis de aloxano (80mg/kg), formándose cinco grupos (n=6), recibiendo los tratamientos vía orogástrica durante ocho días, el grupo I (agua), II (metformina 14mg/kg), grupos III-IV-V zumo de sanky a 1,0; 4,0 y 16 mL/kg, respectivamente. La glicemia fue evaluada por el método rápido (glucómetro) (primer y octavo día). Terminado el tratamiento los animales fueron sacrificados y se les extrajo el páncreas, para su estudio histopatológico. RESULTADOS.: La capacidad antioxidante del EHES mediante el DPPH, mostró un IC50 de 0,77 mg/mL, y por el método FRAP se observó el TEAC-FRAP de 22,31µg/mg. La glicemia disminuyó en el octavo día de tratamiento, respecto al primer día; también se observó disminución de la glicemia en los grupos III-V, respecto al grupo I. A nivel histológico los grupos I-II presentaron atrofia severa y necrosis moderada de los islotes de Langerhans; los grupos IV-V presentaron hipertrofia y necrosis leve multifocal a nivel del islote. CONCLUSIONES.: El extracto de sanky presenta capacidad antioxidante in vitro y el zumo ejerce un efecto hipoglicemiante y protector en páncreas.

Nephroprotective effects of Helianthus annuus seeds extract in gentamicin induced nephrotoxic male mice.

Acute kidney injury (AKI) causes a decrease in renal function which leads to failure in balancing electrolyte, fluid and acid-base homoeostasis. AKI is a damaging and life-threatening disorder, but it can be managed if identified earlier. This study aimed to investigate the possible nephroprotective effect of Helianthus annuus seeds extract against gentamicin (GM) induced nephrotoxicity in male mice. The control group (0.5 ml normal saline i.p.,), Gentamycin (GM) group (GM 100 mg/kg i.p), silymarin + GM group (silymarin 50 mg/kg and GM 100 mg/kg i.p.,), H. annuus extract (HAE) and GM, group (HAE 250 mg/kg and GM 100 mg/kg i.p), HAE2 + GM group (HAE2; 500 mg/kg and GM 100 mg/kg i.p) and H. annuus oil (HAO) + GM (HAO 2.5 ml/kg and GM 100 mg/kg i.p). Serum creatinine, urea and blood urea nitrogen (BUN) were significantly (P< 0.001) elevated in the GM group compared to the control group. The elevated level of serum creatinine, urea and BUN were decreased significantly (P<0.001) in groups treated with HAE and HAO extracts compared to the GM group. The kidney histopathological study from the GM group showed tubular necrosis, vacuolation and fibrosis. However, the animal that received HAE and HAO showed no tubular necrosis and vacuolation. Only mild inflammation was observed compared to the GM group. In conclusion, the extract caused marked radical scavenger and protected the kidney from oxidative damage of GM. H. annuus seeds contain strong antioxidant compounds, including flavonoids, phenolic acids, tocopherols and minerals, which could be responsible for the current show.

Surgical treatment of recurrent intussusception induced by intestinal lymphoid hyperplasia in a child: is bowel resection always necessary? A case report.

BACKGROUND: Intussusception recurrence (IR) induced by intestinal lymphoid hyperplasia (ILH) in children is rare, and surgical treatment is the final resort if IR is refractory to medications and non-surgical interventions. To date, only a few case reports have described surgical management of ILH-induced IR in children, all involving bowel resection regardless of whether there are bowel necrosis and perforation. CASE PRESENTATION: A 2-year-old boy was transferred to our department due to IR. His main complaint was abdominal pain. Color Doppler ultrasound confirmed ileocecal intussusception while no other abnormalities were found. A final diagnosis of IR with unknown causes was made. Repeated saline enema reductions and dexamethasone failed to cure the IR. Laparotomy was eventually performed after almost 10 episodes of IR. Intraoperatively, distal ileum thickening with palpable masses without bowel necrosis and perforation was noted. ILH was suspected and a biopsy of the affected intestine was performed. Histopathological analysis confirmed ILH. The intussusception was manually reduced, the terminal ileum and the ileocecal junction were fixed to the paralleled ascending colon and the posterior peritoneum respectively, and no bowel resection was performed. The postoperative recovery was uneventful and no IR was observed during over 5 years of follow-up. CONCLUSIONS: As far as we are aware, this is the first report of successful surgical treatment of ILH-induced pediatric IR without bowel resection in a child. Our experience suggests bowel resection may be unnecessary if bowel necrosis and perforation are absent.

In Vivo Analysis of Necrosis and Ferroptosis in Nonalcoholic Steatohepatitis (NASH).

Nonalcoholic steatohepatitis (NASH) is a metabolic liver disease that progresses from simple steatosis to the disease states such as chronic inflammation and fibrosis. In most liver diseases, immunological responses caused by tissue damages or viral infection contribute to the pathological advances, and various types of cell death have been reported to be implicated in their pathogenesis. However, the conventional detection of necrosis in vivo is not currently available, whereas the detection method for apoptosis has been relatively well-established. We recently reported a method for the in vivo detection of necrotic cells in liver disease models by an intravenous injection of Propidium Iodide (PI) into mice. We also provide standard methods for the evaluation of lipid accumulation and fibrosis characteristic of NASH. In addition, by utilizing these procedures and a murine model of steatohepatitis, we showed that ferroptosis, a type of regulated necrotic cell death, could be involved in the pathogenesis of NASH. These approaches allow us to explore the pathophysiological roles of cell death in liver diseases.

A multi-strategy platform for quality control and Q-markers screen of Chaiqin chengqi decoction.

BACKGROUND: Acute pancreatitis (AP) is an inflammatory disorder of the pancreas that is associated with substantial morbidity and mortality. Chaiqin chengqi decoction (CQCQD) has been proven clinically to be an effective treatment for AP for decades in West China Hospital. Quality control for CQCQD containing many hundreds of characteristic phytochemicals poses a challenge for developing robust quality assessment metrics. PURPOSE: To evaluate quality consistency of CQCQD with a multi-strategy based analytical method, identify potential quality-markers (Q-markers) based on drug properties and effect characteristics, and endeavor to establish CQCQD as a globally-accepted medicine. METHODS: A typical analysis of constitutive medicinal plant materials was performed following the Chinese Pharmacopoeia. The extraction process was optimized through an orthogonal array (L9(34)) to evaluate three levels of liquid to solid ratio, soaking time, duration of extraction, and the number of extractions. An ultra-high-performance liquid chromatography (UHPLC) fingerprinting combined with absolute quantitation of multi chemical marker compounds, coupled with similarity, hierarchical clustering analysis (HCA), and principal component analyses (PCA) were performed to evaluate 10 batches of CQCQD. On the basis of systematic analysis of fundamental features of CQCQD in treating AP, the potential Q-marker screen was proposed through detection of quality transfer and efficacy for chemical markers. UHPLC coupled with quadrupole orbitrap mass spectrometry were used to determine compounds in medicinal materials, decoctions and plasma. Network pharmacology and taurolithocholic acid 3-sulfate induced pancreatic acinar cell death were used to evaluate the correlation between chemical markers and anti-pancreatitis activity. A cerulein induced AP murine model was used to validate quality assessed CQCQD batches at clinically-equivalent dose. The effective content of chemical markers was predicted using linear regression analysis on quantitative information between validated batches and the other batches. RESULTS: The chemical markers and other physical and chemical indices in the original materials met Chinese Pharmacopoeia standards. A total of 22 co-existing fingerprint peaks were selected and the similarity varied between 0.946 and 0.990. Batch D10 possessed the highest similarity index. HCA classified the 10 batches into 2 main groups: 7 batches represented by D10 and 3 batches represented by D1. During the initial Q-marker screen stage, 22 compounds were detected in both plant materials and decoctions, while 13 compounds were identified in plasma. Network pharmacology predicted the potential targets and pathway of AP related to the 22 compounds. All 10 batches showed reduced necrosis below 60% with the best effect achieved by D10 (~40%). The spectrum-efficacy relationship analyzed by Pearson correlation analysis indicated that emodin, rhein, aloe emodin, geniposide, hesperridin, chrysin, syringin, synephrine, geniposidic acid, magnolol, physcion, sinensetin, and baicalein showed positive correlation with pancreatic acinar cell death protection. Similar to the in vitro evaluation, batch D10 significantly reduced total histopathological scores and biochemical severity indices at a clinically-equivalent dose but batch D1 did not. The content of naringin, narirutin and baicalin in batches D1, D5 and D9 consistently exceeds the upper limit of the predicted value. Eight markers whose lower limit is predicted to be close to 0 contributed less to the material basis for AP protection. CONCLUSION: Despite qualified materials used for CQCQD preparation, the clinical effect depends on appropriate content range of Q-markers. Emodin, rhein, aloe emodin, magnolol, hesperidin, synephrine, baicalein, and geniposide are considered as vital Q-markers in the primary screen. This study proposed a feasible platform for producing highly consistent batches of CQCQD in future study.

Application of Humanized Zebrafish Model in the Suppression of SARS-CoV-2 Spike Protein Induced Pathology by Tri-Herbal Medicine Coronil via Cytokine Modulation.

Zebrafish has been a reliable model system for studying human viral pathologies. SARS-CoV-2 viral infection has become a global chaos, affecting millions of people. There is an urgent need to contain the pandemic and develop reliable therapies. We report the use of a humanized zebrafish model, xeno-transplanted with human lung epithelial cells, A549, for studying the protective effects of a tri-herbal medicine Coronil. At human relevant doses of 12 and 58 µg/kg, Coronil inhibited SARS-CoV-2 spike protein, induced humanized zebrafish mortality, and rescued from behavioral fever. Morphological and cellular abnormalities along with granulocyte and macrophage accumulation in the swim bladder were restored to normal. Skin hemorrhage, renal cell degeneration, and necrosis were also significantly attenuated by Coronil treatment. Ultra-high-performance liquid chromatography (UHPLC) analysis identified ursolic acid, betulinic acid, withanone, withaferine A, withanoside IV-V, cordifolioside A, magnoflorine, rosmarinic acid, and palmatine as phyto-metabolites present in Coronil. In A549 cells, Coronil attenuated the IL-1ß induced IL-6 and TNF-α cytokine secretions, and decreased TNF-α induced NF-κB/AP-1 transcriptional activity. Taken together, we show the disease modifying immunomodulatory properties of Coronil, at human equivalent doses, in rescuing the pathological features induced by the SARS-CoV-2 spike protein, suggesting its potential use in SARS-CoV-2 infectivity.

Discovery of necrosis avidity of rhein and its applications in necrosis imaging.

Necrosis-avid agents possess exploitable theragnostic utilities including evaluation of tissue viability, monitoring of therapeutic efficacy as well as diagnosis and treatment of necrosis-related disorders. Rhein (4,5-dihydroxyl-2-carboxylic-9,10-dihydrodiketoanthracene), a naturally occurring monomeric anthraquinone compound extensively found in medicinal herbs, was recently demonstrated to have a newly discovered necrosis-avid trait and to show promising application in necrosis imaging. In this overview, we present the discovering process of rhein as a new necrosis-avid agent as well as its potential imaging applications in visualisation of myocardial necrosis and early evaluation of tumour response to therapy. Moreover, the molecular mechanism exploration of necrosis avidity behind rhein are also presented. The discovery of necrosis avidity with rhein and the development of rhein-based molecular probes may further expand the scope of necrosis-avid compounds and highlight the potential utility of necrosis-avid molecular probes in necrosis imaging.

A 55-Year-Old Man With Cough and Hematochezia.

CASE PRESENTATION: A 55-year-old man presented to the ED with a 3-week history of worsening cough and shortness of breath. He had blood-tinged sputum, fever, night sweats, and a 2.7 kg weight loss within the same period. For the past few days, he had taken amoxicillin-clavulanate for presumed sinusitis. Despite this, his symptoms persisted, prompting him to seek further evaluation. His medical history was significant for ulcerative colitis and he had some bloody diarrhea for the past few weeks. Medications included aspirin, mesalamine, multivitamins, folic acid, and herbal supplements including gingko biloba, ginseng, and turmeric-ginger. He never smoked and drank alcohol occasionally. Family history was notable for stroke and myocardial infarction.

Effective Nephroprotection Against Acute Kidney Injury with a Star-Shaped Polyglutamate-Curcuminoid Conjugate.

The lack of effective pharmacological treatments for acute kidney injury (AKI) remains a significant public health problem. Given the involvement of apoptosis and regulated necrosis in the initiation and progression of AKI, the inhibition of cell death may contribute to AKI prevention/recovery. Curcuminoids are a family of plant polyphenols that exhibit attractive biological properties that make them potentially suitable for AKI treatment. Now, in cultured tubular cells, we demonstrated that a crosslinked self-assembled star-shaped polyglutamate (PGA) conjugate of bisdemethoxycurcumin (St-PGA-CL-BDMC) inhibits apoptosis and necroptosis induced by Tweak/TNFα/IFNγ alone or concomitant to caspase inhibition. St-PGA-CL-BDMC also reduced NF-κB activation and subsequent gene transcription. In vivo, St-PGA-CL-BDMC prevented renal cell loss and preserved renal function in mice with folic acid-induced AKI. Mechanistically, St-PGA-CL-BDMC inhibited AKI-induced apoptosis and expression of ferroptosis markers and also decreased the kidney expression of genes involved in tubular damage and inflammation, while preserving the kidney expression of the protective factor, Klotho. Thus, due to renal accumulation and attractive pharmacological properties, the application of PGA-based therapeutics may improve nephroprotective properties of current AKI treatments.

Biological safety of Electroacupuncture with STS316 needles.

BACKGROUND: Electroacupuncture (EA) is often used in clinical settings due to its analgesic effect, but its safety has not been verified due to the lack of clear criteria. This study examined the critical range of the corrosion of stainless steel types STS304 and STS316, which have been used clinically, and the relationship between needle corrosion and cell necrosis. METHOD: The critical point of corrosion for STS304 and STS316 was identified by varying the time, frequency, and stimulation intensity. In a tissue necrosis experiment, EA stimulation was applied to rats using STS316 needles with different thicknesses at maximum intensity for 60 min, and the presence of corrosion and tissue necrosis was determined. A cytotoxicity experiment was also conducted and assessed the needles and tissue necrosis. RESULTS: The results showed that STS316 was more stable than STS304 and that only coated needles corroded. Furthermore, tissue necrosis was observed regardless of corrosion, and slight cell necrosis was associated with needles with corrosion. CONCLUSIONS: This study demonstrated that non-coated STS316 was the most stable for EA stimulation and that corrosion byproducts and cell necrosis were not directly related.

Intra-arterial EmboCept S® and DC Bead® effectively inhibit tumor growth of colorectal rat liver metastases.

BACKGROUND: Intra-arterial therapy with embolics is established for the treatment of malignancies of the liver. However, there are no studies comparing the different effects of various embolics used in clinical practice. Herein, we analyzed the effect of 3 different embolics on tumor growth in a rat model of colorectal liver metastases. METHODS: Eight days after subcapsular implantation of 5 × 105 colorectal cancer cells (CC531) in the left liver lobe of WAG/Rij rats were randomized into 4 groups (n = 8) and underwent intra-arterial hepatic therapy. Animals received either EmboCept S®, DC Bead® or Lipiodol® Ultra-Fluid. Animals of the control group received a comparable amount of saline. Tumor growth was measured on day 8 and 11 using a three-dimensional 40 MHz ultrasound device. On day 11 tumor and liver tissue were removed for histological and immunohistochemical analyses. RESULTS: On day 11 animals of the control group showed a tumor growth of ~ 60% compared to day 8. Application of Lipiodol Ultra-Fluid® did not significantly influence tumor growth (~ 40%). In contrast, treatment with EmboCept S® or DC Bead® completely inhibited tumor growth. Of interest, application of EmboCept S® did not only completely inhibit tumor growth but even decreased tumor size. Immunohistochemical analysis showed a significant increase of necrotic areas within the tumors after application of EmboCept S® and DC Bead® compared to Lipiodol® Ultra-Fluid. CONCLUSION: The present study demonstrates that an intra-arterial therapy with EmboCept S® and DC Bead®, but not Lipiodol® Ultra-Fluid, results in a complete inhibition of rat colorectal liver metastatic growth.

An injectable thermosensitive hydrogel for sustained release of apelin-13 to enhance flap survival in rat random skin flap.

With the advantage of handy process, random pattern skin flaps are generally applied in limb reconstruction and wound repair. Apelin-13 is a discovered endogenous peptide, that has been shown to have potent multiple biological functions. Recently, thermosensitive gel-forming systems have gained increasing attention as wound dressings due to their advantages. In the present study, an apelin-13-loaded chitosan (CH)/ß-sodium glycerophosphate (ß-GP) hydrogel was developed for promoting random skin flap survival. Random skin flaps were created in 60 rats after which the animals were categorized to a control hydrogel group and an apelin-13 hydrogel group. The water content of the flap as well as the survival area were then measured 7 days post-surgery. Hematoxylin and eosin staining was used to evaluate the flap angiogenesis. Cell differentiation 34 (CD34) and vascular endothelial growth factor (VEGF) levels were detected by immunohistochemistry and Western blotting. Tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were assessed by enzyme linked immunosorbent assays (ELISAs). Oxidative stress was estimated via the activity of tissue malondialdehyde (MDA) and superoxide dismutase (SOD). Our results showed that CH/ß-GP/apelin-13 hydrogel could not only reduce the tissue edema, but also improve the survival area of flap. CH/ß-GP/apelin-13 hydrogel also upregulated levels of VEGF protein and increased mean vessel densities. Furthermore, CH/ß-GP/apelin-13 hydrogel was shown to significantly inhibit the expression of TNF-α and IL-6, along with increasing the activity of SOD and suppressing the MDA content. Taken together, these results indicate that this CH/ß-GP/apelin-13 hydrogel may be a potential therapeutic way for random pattern skin flap.

The preventive role of wheat germ oil against sertraline-induced testicular damage in male albino rats.

Sertraline is an antidepressant medication used extensively in the therapy of depression. The present investigation was intended to estimate the actual protective role of wheat germ oil on sertraline-caused testicular injury in albino rats. Sertraline (human therapeutic dose, 15.63 mg/kg) was orally administrated to rats for 28 successive days. Sertraline-administered rats were concurrently supplemented with wheat germ oil (human therapeutic dose, 68.75 mg/kg) for 28 successive days. Sertraline administration induced an elevation in testicular DNA damage and acute testicular damage illustrated by the histopathological alterations including marked degeneration and necrosis of germ cells lining seminiferous tubules, as well as interstitial oedema, congestion of interstitial blood vessel. Wheat germ oil administration potentially mitigated the histopathological alterations of sertraline-administered rats. Lipid peroxidation, oxidative stress biomarker, showed a significant elevation in testicular tissue of sertraline-administered rats. Furthermore, glutathione content and catalase activity were decreased in testicular tissue of sertraline-administered rats. Serum testosterone level was elevated in sertraline-administered rats. Wheat germ oil significantly reduced lipid peroxidation of testicular tissue and improved the antioxidant defences. Finally, wheat germ oil has a preventive role against testicular damage induced by sertraline in rats probably via its potential to prevent reactive oxygen species.

Efficacy of Rose Myrtle Rhodomyrtus tomentosa Seed Extract against Acute Hepatopancreatic Necrosis Disease in Pacific Whiteleg Shrimp Penaeus vannamei.

Acute hepatopancreatic necrosis disease (AHPND) is a new emerging bacterial disease that has been recently reported to cause mass mortalities in Pacific whiteleg shrimp Penaeus vannamei. Antibiotics have been used to treat bacterial diseases in shrimp, but most of them have been ineffective and have resulted in drug residues in the harvested shrimp products. In this study, an alternative approach was tested for its efficacy in controlling AHPND. The extract of rose myrtle Rhodomyrtus tomentosa seed, a traditional Vietnamese medicine, was tested for antibacterial effect against three AHPND bacterial strains in vitro (Vibrio parahaemolyticus [VPAHPND ] KC12.020, VPAHPND KC13.14.2, and V. harveyi KC13.17.5) and was further evaluated for its potential efficacy in prevention of AHPND in shrimp in vivo. The in vitro studies showed that the antibacterial activity of the R. tomentosa extract was dose dependent, with the strongest bacterial susceptibility (≥18.0 mm) at a concentration of around 3,500 µg/disc. The in vivo studies showed that after challenge with VPAHPND KC12.020, the survival rates for shrimp in the groups that received feed pellets supplemented with extract at 3.5% or 7.0% (survival ~48.9% and 52.2%, respectively) were significantly higher than the zero survival rate in the positive control group, which received feed without the extract. These results indicate that the use of the R. tomentosa extract as an alternative therapy for control of AHPND in shrimp could help to minimize disease outbreaks. As a result, the extract is further expected to reduce drug/chemical residues in shrimp products.

Omega-3 fatty acids are protective in hepatic ischemia reperfusion injury in the absence of GPR120 signaling.

BACKGROUND: A single dose of IV fish oil (FO) before hepatic ischemia reperfusion injury (HIRI) increases hepatocyte proliferation and reduces necrosis in wild type (WT) mice. It has been suggested that the GPR120 receptor on Kupffer cells mediates FO's ability to reduce HIRI. The purpose of this study was to determine whether GPR120 is required for FO to reduce HIRI. METHODS: Sixty-four (n = 8/group) adult male WT (C57BL/6) and GPR120 knockout (KO) mice received IV FO (1 g/kg) or saline 1 h prior to HIRI or sham operation. Mice were euthanized 24 h postoperatively for analysis of hepatic histology, NFκB activity, and serum alanine transaminase (ALT) levels. RESULTS: FO pretreated livers had less necrosis after HIRI than saline pretreated livers in both WT (mean ±â€¯SEM 25.9 ±â€¯7.3% less, P = 0.007) and KO (36.6 ±â€¯7.3% less, P < 0.0001) mice. There was no significant difference in percent necrosis between WT-FO and KO-FO groups. Sham groups demonstrated minimal necrosis (0-1.9%). Mean [95% CI] ALT after HIRI was significantly higher (P = 0.04) in WT-Saline mice (1604 U/L [751-3427]) compared to WT-FO (321 U/L [150-686]) but was not significantly higher in KO-Saline mice compared to KO-FO. There were no differences in ALT between WT-FO and KO-FO mice who underwent HIRI or between groups who underwent sham surgery. There were no differences in NFκB or IKKß activation among groups as measured by Western blot analysis. CONCLUSIONS: IV FO pretreatment was able to reduce HIRI in GPR120 KO mice, suggesting the hepatoprotective effects of FO are not mediated by GPR120 alone.

Myopathy in a 61-year-old Hispanic man.

A 61-year-old Hispanic man presented to a county hospital for subacute progressive weakness, heliotrope rash and dysphagia. There was initial suspicion for dermatomyositis (DM) given the history; however, the physical exam was not consistent. An MRI followed by a muscle biopsy revealed necrotising autoimmune myositis and anti-3-hydroxy-3-methylglutary-coenzyme A-reductase antibody titers returned positive; the patient was diagnosed with necrotising autoimmune myositis. He was treated with corticosteroids and intravenous immunoglobulin, which resulted in improvement in his weakness and functional status. This case represents a unique instance in which a cardinal feature of DM, the heliotrope rash, prompted an erroneous initial diagnosis. It highlights the necessity of developing abroad differential diagnosis and subsequent thorough investigation into patients presenting with suspected idiopathic immune-mediated myopathies.

Evaluation of the Liver Toxicity of Pterocephalus hookeri Extract via Triggering Necrosis.

Pterocephalus hookeri (C. B. Clarke) Höeck, recorded in the Chinese Pharmacopoeia (2015 version) as a Tibetan medicine for the treatment of various diseases, especially rheumatoid arthritis, was believed to possess a slight toxicity. However, hardly any research has been carried out about it. The present study aimed to evaluate the toxicity in vivo and in vitro. Toxicity was observed by the evaluation of mice weight loss and histopathological changes in the liver. Then, the comparison research between ethyl acetate extract (EAE) and n-butanol extract (BUE) suggested that liver toxicity was mainly induced by BUE. The mechanical study suggested that BUE-induced liver toxicity was closely associated with necrosis detected by MTT and propidium iodide (PI) staining, via releasing lactate dehydrogenase (LDH), reducing the fluidity, and increasing the permeability of the cell membrane. Western blot analysis confirmed that the necrosis occurred molecularly by the up-regulation of receptor-interacting protein kinase 1 (RIP1) and receptor-interacting protein kinase 3 (RIP3), as well as the activation of the nuclear factor-kappa-gene binding (NF-κB) signaling pathway in vivo and in vitro. This finding indicated that the liver toxicity induced by BUE from P. hookeri was mainly caused by necrosis, which provides an important theoretical support for further evaluation of the safety of this folk medicine.

Hyperbaric Oxygen Protects Against Cerebral Damage in Permanent Middle Cerebral Artery Occlusion Rats and Inhibits Autophagy Activity.

BACKGROUND: To investigate the effects of hyperbaric oxygen (HBO) on brain damage and autophagy levels in a rat model of middle cerebral artery occlusion. METHODS: Neurologic injury and infarcted areas were evaluated according to the modified neurological severity score and 2,3,5-triphenyltetrazolium chloride staining. Western blots were used to determine beclin1, caspase-3 and fodrin1 protein expression. Beclin1 protein expression (an autophagy marker), positive terminal dUTP nick-end labeling (TUNEL) staining (an apoptosis marker) and positive propidium iodide (PI) staining (a necrosis marker) were detected by immunofluorescence. RESULTS: Our results indicated that HBO could decrease the infarct volume and speed up the recovery of the neurological deficit scores in ischemic rats. Beclin1 was down-regulated after HBO treatment. HBO treatment inhibited fodrin1 protein expression and decreased the number of PI-positive cells. HBO also down-regulated caspase-3 and decreased the number of TUNEL-positive cells. CONCLUSION: Cerebral ischemia caused early neuronal death due to necrosis, followed by delayed neuronal death due to apoptosis. Consequently, autophagy might be involved in all processes of ischemia. HBO could protect the brain against ischemic injury, and the possible mechanisms might be correlated with decreased autophagy activity and decreased apoptosis and necrosis levels.

Coagulative necrotic pituitary adenoma apoplexy: A retrospective study of 21 cases from a large pituitary center in China.

PURPOSE: Coagulative necrotic pituitary apoplexy (CNPA) is a clinical entity with unique intraoperative and histopathological manifestations. We aimed to improve the knowledge of this rare disease through the largest case series published to date. METHODS: A retrospective review of 21 CNPA patients was performed from among 5095 patients who underwent surgery for pituitary adenomas at a single institution between January 2009 and June 2017. The demographic, clinical, endocrine, neuroimaging, intraoperative, and histopathological findings, management and prognosis were summarized. RESULTS: Headache was the most common symptom that was observed in 21 patients, followed by visual disturbances (17/21, 81.0%), nausea and vomiting (16/21, 76.2%), electrolyte disturbance (13/21, 61.9%), and oculomotor palsies (10/21, 47.6%). Hypopituitarism with at least one anterior pituitary deficiency, especially panhypopituitarism (10/21, 47.6%), was present in 81.0% of patients. Most patients (81.0%) showed typical MRI appearances. All 21 patients underwent transsphenoidal surgery (TSS), and 16 patients had total tumor resection demonstrated by postoperative MRI. Cottage cheese-like necrosis was observed in 16 patients (76.2%) intraoperatively. Histopathology showed large areas of pink, acellular, coagulative necrotic areas in the central zone, and a pseudocapsule in the border zone. After follow-up for 4.3 ± 2.3 years, only 28.6% of patients still suffered from corticotropic deficiency, and 9.5% of patients had gonadotropic deficiency. These patients were administered the appropriate corresponding hormones for life. CONCLUSIONS: CNPA can be correctly diagnosed preoperatively by typical clinical and MRI characteristics. Early surgery combined with hyperbaric oxygen therapy early postoperatively usually yields satisfactory endocrine and neuro-ophthalmic outcomes.

Treatment of deep cavities using a perforator-based island flap with partial de-epithelization.

BACKGROUND: The perforator-based island flap is a popular option for defect coverage. In cases with deep cavities, however, the classical island flap may not be a suitable option. By de-epithelization of the peripheral portion of a perforator-based island flap, the distal part of the flap can be used to fill deep spaces, as the flap can be folded and inserted into the spaces. METHODS: From June 2015 to April 2017, 21 cases of deep internal defects were reconstructed with perforator-based island flaps with peripheral de-epithelization. A fasciocutaneous flap was elevated and rotated with the pivot point on the perforator. After performing de-epithelization on the periphery of the flap, the de-epithelized portion of the flap was inserted and anchored into the internal defect. Demographic information about the patients, the size of the defects, the perforators that were used, and complications were recorded. RESULTS: During the follow-up period (mean, 14.2 months) of total 21 cases, no major complications such as flap loss occurred. In 2 cases, a minor complication was observed. Temporary flap congestion was seen in 1 case, and was treated with a short period of leech therapy, and the other case was partial necrosis on the flap margin, which was cured with minimal debridement and conservative treatment. No major problems have occurred, especially on the de-epithelized part of the flap and in the occupied space. CONCLUSIONS: With performing careful procedure, a perforator-based island flap with partial de-epithelization can be a useful option for the surgical treatment of deep cavities. TRIAL REGISTRATION: This study was retrospectively registered in the institutional review board on human subjects research and the ethics committee, Hanyang University Guri Hospital (Institutional Review Board File No. 2018-01-003-002 https://www.e-irb.com:3443/devlpg/nlpgS200.jsp ).