Colistin, a multidrug-resistant gram-negative bacterial infection medication, has been associated with renal impairment and failure. Trans-sodium crocetinate (TSC), a saffron-derived chemical recognized for its antioxidant and nephroprotective properties, was studied in this study to determine its potential to alleviate the nephrotoxic effects of colistin. Forty-two male Wistar rats were randomly classified into seven groups (n = 6): (1) control (normal saline, 12 days, i.p.), (2) colistin (22 mg/kg, 7 days, i.p.), (3-5) colistin + TSC (25, 50, and 100 mg/kg, 12 days, i.p., starting from 5 days before colistin), (6) TSC (100 mg/kg, 12 days, i.p.), (7) colistin + vitamin E (100 IU/kg, 12 days, i.p). On day 13, the rats were euthanized and the serum content of creatinine, BUN, Na+, and K+, as well as oxidative stress (GSH, MDA, SOD, CAT), inflammatory (IL-1β), apoptotic (Bax, Bcl-2, caspase-3, 8, 9), and autophagy (Beclin-1, LC3) markers, NGAL, and histopathological changes in the kidney were measured. Colistin significantly increased serum creatinine, BUN, MDA, IL-1β, caspase-3,8,9, Bax, Beclin-1, LC3, and NGAL levels in kidney tissue. It also caused inflammation, focal necrosis of tubular epithelial cells, protein cast, and acute tubular necrosis. Furthermore, colistin decreased SOD, CAT, GSH, and Bcl-2 levels. TSC and vitamin E administration along with colistin restored most of the alterations induced by colistin. Overall, it could be concluded that colistin induces oxidative stress, inflammation, autophagy, and apoptosis, which can cause kidney injury. However, TSC can also be used as a therapeutic agent to reduce injuries caused by colistin.

Clostridioides difficile (C. difficile) is responsible for a spectrum of nosocomial/antibiotic-associated gastrointestinal diseases that are increasing in global incidence and mortality rates. The C. difficile pathogenesis is due to toxin A and B (TcdA/TcdB), both causing cytopathic and cytotoxic effects and inflammation. Recently, we demonstrated that TcdB induces cytopathic and cytotoxic (apoptosis and necrosis) effects in enteric glial cells (EGCs) in a dose/time-dependent manner and described the underlying signaling. Despite the role played by lipids in host processes activated by pathogens, to counter infection and/or induce cell death, to date no studies have investigated lipid changes induced by TcdB/TcdA. Here, we evaluated the modification of lipid composition in our in vitro model of TcdB infection. Apoptosis, cell cycle, cell viability, and lipidomic profiles were evaluated in EGCs treated for 24 h with two concentrations of TcdB (0.1 ng/mL; 10 ng/mL). In EGCs treated with the highest concentration of TcdB, not only an increased content of total lipids was observed, but also lipidome changes, allowing the separation of TcdB-treated cells and controls into different clusters. The statistical analyses also allowed us to ascertain which lipid classes and lipid molecular species determine the clusterization. Changes in lipid species containing inositol as polar head and plasmalogen phosphatidylethanolamine emerged as key indicators of altered lipid metabolism in TcdB-treated EGCs. These results not only provide a picture of the phospholipid profile changes but also give information regarding the lipid metabolism pathways altered by TcdB, and this might represent an important step for developing strategies against C. difficile infection.

Setd8 regulates transcription elongation, mitotic DNA condensation, DNA damage response and replication licensing. Here we show that, in mitogen-stimulated liver-specific Setd8-KO mice, most of the hepatocytes are eliminated by necrosis but a significant number of them survive via entering a stage exhibiting several senescence-related features. Setd8-deficient hepatocytes had enlarged nuclei, chromosomal hyperploidy and nuclear engulfments progressing to the formation of intranuclear vesicles surrounded by nuclear lamina. These vesicles contain glycogen, cytoplasmic proteins and even entire organelles. We term this process \"endonucleosis\". Intranuclear vesicles are absent in hepatocytes of Setd8/Atg5 knockout mice, suggesting that the process requires the function of the canonical autophagy machinery. Endonucleosis and hyperploidization are temporary, early events in the surviving Setd8-deficient cells. Larger vesicles break down into microvesicles over time and are eventually eliminated. The results reveal sequential events in cells with extensive DNA damage, which function as part of survival mechanisms to prevent necrotic death.

BACKGROUND: Sarcoidosis is a multisystem inflammatory disease with a variable presentation. The most characteristic feature of sarcoidosis is nonnecrotizing granulomas. However, when sarcoidosis presents with rare organ involvement, and biopsy shows necrosis, the diagnosis becomes challenging.
METHODS: Here, we present three cases of sarcoidosis with unusual organ involvement and biopsy findings of necrosis, leading to a delay in diagnosis and treatment. Case 1 was presented with lymphoreticular involvement within the intraparotid lymph node and genitourinary area. Biopsy from the epididymis showed necrosis, initially leading to treatment for tuberculosis (TB). Case 2 describes lymphoreticular involvement and cardiac symptoms. His cervical and bone marrow biopsies showed necrosis. Case 3\'s presentation was disseminated lymphadenopathy with hepatosplenomegaly, initially suspected as malignancy or TB.
CONCLUSIONS: While biopsy plays a significant role in diagnosing sarcoidosis, the presence of necrosis alone should not lead to its exclusion.

UNASSIGNED: Diode laser is one of the most captivating technologies in dental practice. In periodontics, when used at appropriate settings, it possesses the best properties for selective surgical and nonsurgical procedures such as subgingival calculus removal without a thermal change of the root surface, and also provides tissue surface sterilization. However, lasers always produce a certain amount of thermal damage to the soft tissues. Therefore, this study aimed to comparatively evaluate the thermal impact of 980-nm diode laser incisions, when used with irrigation versus nonirrigation systems.
UNASSIGNED: The study was conducted on 24 gingival tissue samples obtained from the goat\'s mandible and maxilla. The samples were divided into two groups of 12 samples each, and laser incisions were given in 4 power settings, using 980-nm diode laser in super short pulse mode, with and without saline irrigation. Martius Scarlet Blue staining technique was used to prepare the histological slides. Then, slides were examined under a research microscope (Olympus CX 21), and the pictures of the slides were taken by mounting the camera onto the microscope mobile mount. The microscopic images hence obtained were analyzed for the depth and width of the incisions, area of carbonization, necrosis, and reversible damage, using the Digimizer image analysis software.
UNASSIGNED: The results of this study demonstrated that the mean incision depth was higher (592.49 ± 180.97, P < 0.05), with less carbonization (25.52 ± 29.21, P = 0.00) and less necrosis (311.63 ± 156.441, P < 0.05) in the laser incisions with irrigation, as compared to the laser incisions given without irrigation system.
UNASSIGNED: Within the limitations of this study, it can be concluded that using an irrigation system causes less collateral damage while maintaining the incising efficiency of the diode laser. Further studies with a higher sample size, controlled irrigation systems, and incision techniques are needed to evaluate the efficiency of diode lasers for the clinical explanation of the results.

Acute pancreatitis (AP) is a life-threatening inflammatory disease with no specific therapy. Excessive cytoplasmic Ca2+ elevation and intracellular ATP depletion are responsible for the initiation of AP. Inhibition of Ca2+ release-activated Ca2+ (CRAC) channels has been proposed as a potential treatment, and currently, a novel selective CRAC channel inhibitor CM4620 (Auxora, CalciMedica) is in Phase 2b human trials. While CM4620 is on track to become the first effective treatment for AP, it does not produce complete protection in animal models. Recently, an alternative approach has suggested reducing ATP depletion with a natural carbohydrate galactose. Here, we have investigated the possibility of using the smallest effective concentration of CM4620 in combination with galactose. Protective effects of CM4620, in the range of 1-100 n m, have been studied against necrosis induced by bile acids, palmitoleic acid, or l-asparaginase. CM4620 markedly protected against necrosis induced by bile acids or asparaginase starting from 50 n m and palmitoleic acid starting from 1 n m. Combining CM4620 and galactose (1 m m) significantly reduced the extent of necrosis to near-control levels. In the palmitoleic acid-alcohol-induced experimental mouse model of AP, CM4620 at a concentration of 0.1 mg/kg alone significantly reduced edema, necrosis, inflammation, and the total histopathological score. A combination of 0.1 mg/kg CM4620 with galactose (100 m m) significantly reduced further necrosis, inflammation, and histopathological score. Our data show that CM4620 can be used at much lower concentrations than reported previously, reducing potential side effects. The novel combination of CM4620 with galactose synergistically targets complementary pathological mechanisms of AP.

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The liver is a remarkable organ that can regenerate in response to injury. Depending on the extent of injury, the liver can undergo compensatory hyperplasia or fibrosis. Despite decades of research, the molecular mechanisms underlying these processes are poorly understood. Here, we developed a new model to study liver regeneration based on cryoinjury. To visualise liver regeneration at cellular resolution, we adapted the CUBIC tissue-clearing approach. Hepatic cryoinjury induced a localised necrotic and apoptotic lesion characterised by inflammation and infiltration of innate immune cells. Following this initial phase, we observed fibrosis, which resolved as regeneration re-established homeostasis in 30 days. Importantly, this approach enables the comparison of healthy and injured parenchyma with an individual animal, providing unique advantages to previous models. In summary, the hepatic cryoinjury model provides a fast and reproducible method for studying the cellular and molecular pathways underpinning fibrosis and liver regeneration.

BACKGROUND: Abdominal cocoon is a very uncommon yet dangerous cause of intestinal obstruction.
METHODS: We present a case of a 62-year-old Asian male patient with a history of depression who exhibited an idiopathic abdominal cocoon complicated by necrosis. Upon laparotomy investigation, nearly the entire small intestine was enveloped in a thick membrane resembling a cocoon, and it was discovered that he lacked a greater omentum. The patient recovered well and was discharged on an oral diet on the 20th day following surgery. During the 3-month follow-up, the patient was asymptomatic, even gaining 10 kg in weight, and noted that his depression had improved.
CONCLUSIONS: Small bowel obstruction presents with nonspecific symptoms, posing challenges in differential diagnosis. Contrast-enhanced computed tomography is recommended since it facilitates precise preoperative assessment, optimizing surgical planning and reducing postoperative complications. Remarkably, cessation of antidepressant medication post-surgery hints at a potential correlation between omental deficit, gut microbiota alterations, and depressive symptoms.

BACKGROUND: Descending necrotizing mediastinitis (DNM) is a rare but serious complication of oral and cervical infections that is associated with high mortality because diagnosis can be difficult or delayed. Early diagnosis and accurate identification of the causative pathogen can significantly reduce mortality, and are critical for the management of these patients.
METHODS: A 56-year-old female was admitted with a sore throat and fever. The initial diagnosis was acute tonsillitis, but she was transferred to the intensive care unit after developing dyspnea.
METHODS: Pleural effusion and mediastinal lesions were detected by computed tomography, and a diagnosis of DNM was confirmed by laboratory tests.
METHODS: Initial treatment consisting of ceftriaxone and vancomycin with chest tube drainage were not effective. Thoracic surgery was performed to completely remove the \"moss\" tissue, blood clots, and pus. Next-generation sequencing was then performed, and the anti-infective treatment was changed to imipenem and linezolid based on these results.
RESULTS: Eventually, the patient\'s symptoms were controlled, all vital signs were stable, and she was successfully transferred out of the intensive care unit.
CONCLUSIONS: Next-generation sequencing is a rapid and accurate method for identification of pathogens that can provide a basis for early treatment of DNM, thereby improving patient prognosis and reducing mortality.