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Based on the gathered results, it is concluded that ascorbate and CA demonstrate comparable ameliorative and protective effects against DMN-induced renal and testicular toxicities in rats.Cardiotoxicity is one of the severe adverse effects of chemotherapeutic agents. Imatinib was previously reported to induce cardiotoxicity. Autophagy is an intracellular bulk protein and organelle degradation process, but its roles in cardiac diseases are unclear. selleck chemical We examined whether imatinib induces cardiomyocyte autophagy, and the role of autophagy in imatinib-induced cardiotoxicity using in vitro and in vivo experiments. In in vitro experiments, neonatal rat cardiomyocytes were treated with imatinib (1, 5, or 10 μM; 6 h). Myocyte autophagy was assessed by microtubule-associated protein light chain (LC) 3-II, beclin 1, mature cathepsin D, and acridine orange-stained mature autolysosome expression. Imatinib increased their expression, suggesting that it induced autophagy. Consequently, imatinib altered the production of mitochondria-derived reactive oxygen species (ROS) and loss of mitochondrial membrane potential, which were assessed by the fluorescent indicator MitoSOX and JC-1, respectively, leading to cardiomyocyte apoptosis. 3-methyl-adenine (3MA), an autophagic inhibitor, exacerbated imatinib-induced apoptosis by 30 %. In in vivo experiments, C57BL/6 mice were treated with imatinib (50 and 200 mg/kg/day) for 5 weeks in the presence or absence of 3MA. Echocardiographic measurement revealed that imatinib (200 mg) caused dilatation of the left ventricle (LV) and reduced LV fractional shortening. Apoptosis and LC3-II expression in cardiac tissue were increased by imatinib. Co-treatment with 3MA and imatinib further impaired imatinib-induced cardiac apoptosis and LV dysfunction. This study suggests that imatinib induces cardiomyocyte apoptosis, leading to cardiac dysfunction. Imatinib increases cardiomyocyte autophagy as a consequence of apoptosis and autophagy has a pro-survival role in imatinib-induced cardiac impairment.We present a very rare case of fatal complication during the cardiac surgery caused by unrecognized solitary metastasis of clear cell renal cell carcinoma in the sternum.We report a 31 year old female with urologic history significant for right ureteropelvic junction obstruction managed with open right pyeloplasty in 1996 with recurrent stricture managed with right ureterocalycostomy in 1997 along with right distal ureteroneocystostomy for iatrogenic distal ureteral stricture. She developed symptomatic stone episodes and recurrent urinary tract infections and elected to proceed with shockwave lithotripsy. Postoperatively she developed a large liver hemorrhage requiring supportive care and endovascular embolization.Vestronidase alfa is an enzyme replacement therapy for mucopolysaccharidosis VII (MPS VII). In this open-label, phase 1/2 study, three subjects with MPS VII received intravenous vestronidase alfa administered every other week (QOW) for 14 weeks (2 mg/kg), followed by 24-week forced-dose titration (1, 4, and 2 mg/kg QOW; 8 weeks each), 36-week continuation (2 mg/kg), and long-term extension (4 mg/kg). Vestronidase alfa was well tolerated and led to dose-responsive, sustained reductions in urinary glycosaminoglycan excretion.Drug-induced lysosomal storage disease (DILSD) caused by cationic amphiphilic drugs (CADs), which exhibits toxic manifestations and pathological findings mimicking Fabry disease (α-galactosidase A deficiency), has attracted the interests of clinicians and pathologists. Although the affected region is lysosomes in both the diseases, DILSD is characterized by intralysosomal accumulation of phospholipids and Fabry disease that of globotriaosylceramide (Gb3) and globotriaosylsphingosine (Lyso-Gb3). However, it is unknown whether administration of CADs affects the catabolism of Gb3 and Lyso-Gb3 in Fabry disease. In this study, we independently administered hydroxychloroquine/amiodarone to wild-type and Fabry mice and examined the effects of the drugs on the enzyme activity and substrates accumulated in organs and tissues. The results revealed that the administration of the drugs induced accumulation of phosphatidylcholine in both the wild-type and Fabry mice. However, reduction of α-galactosidase A activity in the organs and tissues of the wild-type mice was not found, and the storage of Gb3 and Lyso-Gb3 was not accelerated by these drugs in the Fabry mice. This suggests that hydroxychloroquine/amiodarone do not have any significant impact on the catabolism of Gb3 and Lyso-Gb3 in organs and tissues of both wild-type and Fabry mice.

SARS-CoV-2 uses the human cell receptor angiotensin-converting enzyme (ACE2). ACE2 is widely present in the cardiovascular system including the myocardium and the conduction system. COVID-19 patients that present severe symptoms have been reported to have complications involving myocardial injuries caused by the virus. Here we report the detection of SARS-CoV-2 by whole genome sequencing in the endocardium of a patient with severe bradycardia.

We report a case of a 34-year-old male patient with COVID-19 tested by PCR, he started with gastrointestinal symptoms, however, he quickly deteriorated his hemodynamic state by means of myocarditis and bradycardia. After performing an endocardium biopsy, it was possible to identify the presence of SARS-CoV-2 in the heart tissue and to sequence its whole genome using the ARTIC-Network protocol and a modified tissue RNA extraction method. The patient's outcome was improved after a permanent pacemaker was implanted.

It was possible to identify a SARS-CoV-2 clade 20A in the endocardium of the reported patient.

It was possible to identify a SARS-CoV-2 clade 20A in the endocardium of the reported patient.Ignatzschineria spp. bacteremia associated with maggot infestation is extremely rare in humans. There are only a few cases worldwide ever reported in the literature. We described a clinical case with a male patient who presented with maggot manifestation at his lower extremity, was found with bacteremia, and subsequently identified as Ignatzschineria spp by 16S rRNA sequencing.

The function of H3F3A G43W mutation, which has been observed in almost all GCTB, remains poorly characterized. Breakthrough in malignant GCTB has been trapped by the lack of clinical available drugs, limited canonical patient samples and paucity of fidelity preclinical models.

Tumor samples obtained from a malignant GCTB was implanted in immunodeficient mice for the generation of PDX. Histological examination and short tandem repeat (STR) were used for inherited features analyses. An epigenetic/transcriptional targeted compound library was selected for drug screening. The in vivo effects of selected drug were validated in PDX model.

We established the PDX model with recurrent malignant GCTB specimens, histological examination and STR analyses revealed that PDX and their corresponding parental patients shared the same STRs and histologic features, suggesting common origins. ITF-2357 was the most significant compound with an IC50 lower than 0.1 uM. The results of the drug screening and in vivo PDX validation demonstrated that ITF-2357 might be a promising drug targeted H3F3A G34W mutation MGCTBs.

Our study demonstrates that PDX model maintained the same histologic and genetic features as those in the original patient. targeting HDAC through ITF-2357 effectively overcomes malignant GCTB progression in vitro and in vivo.

As PDX retain the principal histologic and genetic characteristics of the primary tumors, mad it a valuable research tool in predictive clinical efficacy. In this study, we first established a malignant GCTB PDX model, which might further accelerate the progress of drug development in malignant GCTB.

As PDX retain the principal histologic and genetic characteristics of the primary tumors, mad it a valuable research tool in predictive clinical efficacy. In this study, we first established a malignant GCTB PDX model, which might further accelerate the progress of drug development in malignant GCTB.

Ischemic diabetic foot ulcer is one of the terminal complications of diabetes. The high amputation rate, recurrence rate, and treatment cost have caused a huge burden on patients and society. This study designed the modified tibial transverse transport (mTTT) technology to treat diabetic ischemic diabetic foot ulcers in patients with type 2 diabetes and investigated the effectiveness and safety of this technique.

This was a retrospective analysis of patients with type 2 diabetes and ischemic diabetic foot ulcers at two hospitals during January 2016-October 2019. These patients underwent mTTT surgery combined with wound debridement and vacuum sealing drainage negative pressure drainage treatment. In-hospital follow-up was performed at 1 month after the operation, while outpatient follow-up was performed at 3, 6, and 12 months after the operation. The ulcer healing time, recurrence rate, major amputation rate, and complications were analysed.

A total of 201 patients were enrolled in this study, including cal application and was worthy of further clinical research with high evidence level.

Tunnel position deicide the isometry of graft attachment in synthetic anterior cruciate ligament (ACL) reconstruction. Near-isometric tunnel position may have advantage in graft integration and knee function in ACL reconstruction (ACLR) with polyethylene terephthalate (PET) ligament. Few studies focused on tunnel position isometry when conduct ACLR with an animal model. This study aimed to establish a preclinical rabbit model of near and non isometric ACLR with PET ligament and investigate the advantage of near-isometric ACLR compared to non-isometric ACLR.

Nine hind limbs of rabbit were used in tunnel position study. Two femoral(anatomic, nonanatomic) tunnels and three tibial(anterior, middle, posterior) tunnels were used to measure tunnel position isometry during knee full range of motion. The tunnel position combination with minimal isometry was considered as near-isometric tunnel position. Then, 48 rabbits divided into two groups were conducted near or non isometric ACLR with PET ligament with graft fmonstrate the establishmentof near-isometric tunnel position and non-isometric tunnel position with significant difference of ROM restriction and graft-bone integration. The described tunnel positions with differential isometry in a rabbit ACLR provides a reproducible and translational small animal model and enables preclinical research between tunnel position isometry and its affection on variable grafts, graft integration and knee function.

Japanese Kampo medicine is a traditional medicine with roots in ancient Chinese medicine. Because traditional physicians had been abolished in Japan, the present mainstream of Kampo treatment is that physicians who learned modern Western medicine prescribe Kampo extract products based on Western medical diagnosis. This situation is different from that in other east Asian countries, and the physicians require scientific clinical evidence.

Clinical studies were searched from literature databases, clinical trial registry sites, and "Evidence Reports of Kampo Treatment (EKAT)" published by the Japan Society for Oriental Medicine.

At the approval of Kampo products, scientific clinical evidence was not required because they have a long-period experience as a decoction. However, in the 1990s, Kampo products became a subject for national reevaluation; double-blind and placebo-controlled clinical trials. At the time, a methodological foundation for conducting clinical assessments of Kampo medicines was established.