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Background: Atrial fibrillation is common in patients with structural heart disease who are undergoing cardiac surgery. Surgical CryoMaze has been shown to be an effective treatment in several trials, but success rates have varied considerably, between 47-95%. The sequential hybrid approach, combining surgical CryoMaze followed by radiofrequency catheter ablation, can achieve high freedom from atrial arrhythmias. However, in patients with concomitant surgical atrial fibrillation treatment, data comparing the hybrid approach to CryoMaze alone are lacking. Methods: The SurHyb study was designed as a prospective, open-label, multicentre randomized trial. Patients with non-paroxysmal atrial fibrillation who were scheduled for coronary artery bypass grafting or valve repair/replacement were randomized to either surgical CryoMaze alone or surgical CryoMaze followed by radiofrequency catheter ablation 3 months post-surgery. The primary outcome measure was arrhythmia-free survival without class I or III antiarrhythmic drugs, which has been evaluated using implantable cardiac monitors. Conclusions: This is the first randomized study that compares concomitant surgical CryoMaze alone with the staged hybrid surgical CryoMaze followed by catheter ablation, in patients with non-paroxysmal atrial fibrillation using rigorous rhythm monitoring. The results may contribute to the optimization of the treatment in patients undergoing concomitant CryoMaze for atrial fibrillation.

Introduction: Papillary thyroid carcinoma (PTC) frequently harbors the BRAF V600E mutation. Recent research suggests that aggressive behavior in BRAF V600E+ PTC may be due to an undetected mutation in the TERT gene. This study aims to observe the clinicopathological features of BRAF V600+ PTC and correlate them with surgical treatment complications. Methods: A retrospective analysis was conducted on the BRAF V600E+ PTC cohort from July 2019 to January 2023. The histopathological features and surgical treatment (total thyroidectomy - group A, total thyroidectomy + central block neck dissection - group B) complications were correlated. Patients with TERT and TP53 mutation were excluded. Next-generation sequencing and real-time PCR were used for genetic analysis. Results: Out of 121 PTCs, 65 cases showed BRAF V600E mutation with the following features: intracapsular spread (13.8%), extracapsular spread (27.7%), extrathyroidal spread (15.4%), multifocality (26.2%), angioinvasion (12.3%), and local metastasis (27.7%). The incidence of surgical complications in group A/B was: reversible recurrent laryngeal nerve (RLN) paresis 3.7/7.1%, RLN paresis permanent 0/2.4%, paresthesia 6.8/23.8%, hypocalcemia 36.4/61.9% on day 1 and 27.3/33.3% on day 3, and bleeding 2.3/9.5%. There was no significant difference in clinicopathological features between the BRAF V600E+ and BRAF V600E- PTC groups. Group B had a significantly higher incidence of hypoacalcaemia on postoperative day 1 (p = 0.047). Conclusion: The BRAF V600E mutation will certainly remain important in the preoperative diagnosis of PTC. The more radical surgical procedures currently recommended may be abandoned in the future, particularly elective CLND, which has a higher risk of postoperative complications.

The aim of this study was to assess 17-β-estradiol (E2) influence on sciatic nerve regeneration after injury followed by a repair with chitosan conduit in ovariectomized female rats. The study was performed in 2 groups (n = 16) of rats: OVChit - after excision of a fragment of the sciatic nerve, a chitosan conduit was implanted; OVChitE10 group - additionally to chitosan conduit, shape-memory terpolymer rods based on poly(L-lactide-co-glycolide- co-trimethylene carbonate) releasing 17-β-estradiol for 20 weeks were implanted. The mean number of regenerating axons and mean fiber area were significantly greater in 17-β-estradiol-treated animals. In this group, the infiltrate of leukocytes was diminished. The presence of 17-β-estradiol receptors alpha and beta in motoneurons in the spinal cord were discovered. This may indicate the location where 17-β-estradiol affects the regeneration of the injured nerve. Estradiol released from the terpolymer rods for 20 weeks could enhance, to some extent, sciatic nerve regeneration after injury, and diminish the inflammatory reaction. In the future, 17-β-estradiol entrapped in terpolymer rods could be used in the repair of injured peripheral nerves, but there is a need for further studies.

Breast cancer is a serious public problem in modern society. Photodynamic therapy (PDT) is increasingly used in modern medicine. Currently, PDT is an innovative method of treating breast cancer. Irreversible damage to neoplastic tissues is associated with the use of physicochemical processes. Generating cytotoxic reactive oxygen species [singlet oxygen (1O2)] is leading to tumor cell death. At the same time, valuable information can be extracted from breast cancer cells. Photogenerated 1O2 is the major factor responsible for cell necrosis during PDT. 1O2 can react rapidly intracellularly with all organic substances. The use of photodynamic therapy on tissues in vitro creates conditions for testing various types of solutions and implementing them in in vivo treatment. This article is a review of recent advances in PDT for treatment of breast cancer. PDT is a novel cancer diagnostic and cancer treatment therapy. Therefore, an understanding of the possibility to generate a toxic form of 1O2 is necessary. The knowledge gained from the basics of PDT in vitro can be useful in biomedical applications in vivo. The current literature mentions PDT in the treatment of cancers located very deep within the human body. Therefore, the development of agents used to deliver 1O2 to the deep cancerous tissue is a new challenge which can have an efficient impact on this discipline. This review covers the literature between 2000-2022.

Infections caused by Methicillin-Resistant Staphylococcus aureus (MRSA) and Extended-Spectrum Beta-Lactamase (ESBL) producing Enterobacter cloacae are considered as major therapeutic challenge due to their multidrug-resistant (MDR) phenotype against conventional antibiotics. WLBU2 is an engineered cationic peptide with potent antimicrobial activity. This in-vitro study aimed to evaluate the effects of WLBU2 against clinical isolates of the aforementioned bacteria and assess whether synergistic effects can be achieved upon combination with conventional antibiotics. The minimum inhibitory concentrations (MICs) of antimicrobial agents against bacterial clinical isolates (n = 30/strain) were determined using the microbroth dilution assay. The minimum bactericidal concentrations (MBCs) of WLBU2 were determined from microbroth dilution (MICs) tests by subculturing to agar plates. MICs of WLBU2 were evaluated in the presence of physiological concentrations of salts including NaCl, CaCl2 and MgCl2. To identify bacterial resistance profile, MRSA were treated with Oxacillin, Erythromycin and Vancomycin, while Ceftazidime, Ceftriaxone, Ciprofloxacin and Imipenem were used against Enterobacter cloacae. Combination treatments of antibiotics and sub-inhibitory concentrations of WLBU2 were conducted when MICs indicated intermediate/resistant susceptibility. The MICs/MBCs of WLBU2 were identical for each respective bacteria with values of 0.78-6.25 μM and 1.5-12.5 μM against MRSA and Enterobacter cloacae, respectively. WLBU2 was found as salt resistant. Combination treatment showed that synergistic and additive effects were achieved in many isolates of MRSA and Enterobacter cloacae. Our data revealed that WLBU2 is a potent peptide with bactericidal activity. In addition, it demonstrated the selective advantage of WLBU2 as a potential therapeutic agent under physiological solutions. Our findings also support the combination of WLBU2 and conventional antibiotics with potential application for treatment of resistant bacteria.

Cancer research is linked to modern life-sciences, encompassing achievements in virology, yeast-biology, molecular-biology, genetics, systems-biology, bioinformatics, and so on. With these fascinating developments, it's easy to overlook that the fundamental theories and treatment strategies were established in the early 20th century and have remained valid ever since. Therefore, tribute must be paid to the founders of the field. The main hypotheses on carcinogenesis, the genetic model and the metabolic model, and the concept of cancer-treatment with cytotoxic, targeted or metabolic drugs were proposed more than 100 years ago by great minds such as T. Boveri, O. Warburg, and P. Ehrlich. Hence nothing about these cancer concepts is really new. Through development of powerful new technologies, we have been able to decipher the mechanisms of malignant transformation, thus significantly advancing the field. Our own studies have been focused on the cross-talk between cell-growth-signaling and lipid-metabolism in ovarian cancer to find crossover-points for co-targeting in order to achieve synergistic treatment effects. Notably, a side-effect of the application of current methods of molecular-cell-biology is a deeper knowledge of the laws of normal cell-biology and cell-life. Thus we anticipate the field will advance rapidly in the near future.

Dose-limiting nephrotoxicity restricts Cisplatin use in high therapeutic doses. Empagliflozin showed a reno-protective effect in diabetic nephropathy. We investigated if Empagliflozin can ameliorate Cisplatin nephrotoxicity whether used prophylactically or therapeutically. Forty male Wistar rats were divided into 5 groups: (1) control; (2) Cisplatin-induced nephrotoxicity by single intraperitoneal dose; (3) Empagliflozin was given for 10 days before a single dose of Cisplatin; (4) a single dose of Cisplatin followed by Empagliflozin for 10 days; (5) received Empagliflozin only. Regular assessment of weight was done, biochemical evaluation for serum urea, creatinine, uric acid, albumin, and glucose was performed, kidney tissue nerve growth factor-β (NGF-β) and oxidative stress parameters were measured, kidneys were evaluated histopathologically and immunostained for caspase 3. Cisplatin significantly reduced body weight, NGF-β, and reduced glutathione, elevated urea, creatinine, and malondialdehyde with no effect on other serum biochemical parameters. Histopathologically, there was high acute tubular necrosis (ATN) score with strong immunostaining of caspase 3. The use of Empagliflozin significantly reduced urea and creatinine in both prophylactic and therapeutic, reduced ATN score in the prophylactic group associated with minimal staining of caspase 3 and elevated reduced glutathione. In conclusion, prophylactic Empagliflozin protected against Cisplatin-induced acute kidney injury mainly via anti-apoptotic effect.

Bromobenzene is a compound which has contributed much in understanding the mechanisms involved in xenobiotic hepatotoxicity induced by drugs and environment pollutants. In the present study, the protective and ameliorative effect of beta-carotene was investigated against bromobenzene-induced hepatotoxicity and compared with silymarin, a standard hepatoprotective reference drug. Beta-carotene (10 mg/kg b.w. p.o.) was administered to the rats for 9 days before intragastric intubation of bromobenzene (10 mmol/kg b.w.). Liver marker enzymes (aspartate transaminase, alanine transaminase and alkaline phosphatase), total protein content, bilirubin, total cholesterol, high-density lipoproteins, triglycerides, antioxidant status (reduced glutathione, superoxide dismutase, catalase, glutathione-S-transferase and glutathione peroxidase) were assessed along with histopathological analysis. ELISA was performed for analysing the levels of cytokines such as TNF-α, IL-1β and IL-6 in serum and in the liver. Caspase-3, COX-2 and NF-κB were evaluated by Western blotting. Administration of bromobenzene resulted in elevated levels of liver marker enzymes, bilirubin, lipid peroxidation and cytokines but deterioration in total protein content, antioxidant levels and histopathological conditions. Pre-treatment with beta-carotene not only significantly decreased the levels of liver markers, lipid peroxidation and cytokines but also improved histo-architecture and increased antioxidant levels minimising oxidative stress, and reduced factors contributing to apoptosis. This significant reversal of the biochemical changes on pre-treatment with beta-carotene in comparison with rats administered with bromobenzene clearly demonstrates that beta-carotene possesses promising hepatoprotective effect through its antioxidant, anti-inflammatory and antiapoptotic activity and hence is suggested as a potential therapeutic agent for protection from bromobenzene.

Background: Femoral posterior hip dislocation with associated femoral head fractures (Pipkin fractures) are rare high-energy injuries. Published treatment modalities involve conservative treatment, head fragment resection, open reduction and internal fixation, and total hip replacement. The experience with mini-invasive screw osteosynthesis of these fractures is the main focus of our study. Methods: Seven Pipkin fractures (five Pipkin II and two Pipkin I) in six patients were treated by closed reduction of hip dislocation, followed by minimal invasive lag screw osteosynthesis. Cancellous screw(s) were inserted from the incision on the lateral hip through the femoral neck to the reduced fracture fragment. In all patients, postoperative CT was performed to check the quality of surgery. Active physiotherapy with immediate toe-touch weight bearing was the routine postoperative protocol. In all patients, radiological and clinical results were evaluated with the Thompson Epstein, Merle d'Aubigne and Postel score, and Harris hip score. Results: All fractures united, and all femoral heads survived. Infectious complications were not observed, and no secondary surgery was needed. After an average follow-up of 18.4 months, the average Merle d'Aubigne and Postel score was 17.7 points, while the mean Harris hip score reached 98.1 points. The majority of patients achieved an excellent Thompson-Epstein clinical and radiological outcome. All patients returned to their original occupation. Conclusions: Mini-invasive screw osteosynthesis can be used for the treatment of Pipkin type I-II femoral head fractures. Successful reduction of hip dislocation and head fracture is necessary for using this technique. Long-term follow-up is necessary to confirm this technique.

Equipment for fast and accurate detection of organophosphate nerve agents is developed and tested. The method is based on the spectrophotometric monitoring of the enzyme activity of butyrylcholinesterase after its contact with air in a special absorption unit (a "scrubber") developed for the purpose. The scrubber was made from a glass tube filled with glass beads (diam. 3 mm) and filled with approx. 5 ml of butyrylcholinesterase in a phosphate buffer of pH 7.4. The air sample was bubbled through this solution for 20 s at a flow rate of 80 l hour^-1. Thereafter 8 μl of the enzyme solution were aspirated into the micro-SIA-LOV analyzer and the activity of the enzymes were evaluated by using Ellman's reagent, i.e. 2.5 mmol l^-1 butyrylthiocholine iodide and 0.25 mmol 5,5'-dithiobis (2-nitrobenzoic acid). The absorbance of the coloured reaction product was measured at 412 nm after the reaction time of 60 s. The residue of the absorption liquid was washed away from the absorber and the system was washed with the enzyme solution prior to next analysis. The contaminated air caused partial inhibition of the enzyme activity of the absorption liquid. The activity of the contaminated sample was compared with the activity of the unaffected enzyme (blank measurement). The analysis was controlled by two PCs. The effect of the concentration of analyte in the absorption liquid on the enzyme activity was tested for 10^-5-10^-9 mol l^-1 sarin. A single analysis (including the absorption step) took

The role of asymptomatic infections caused by Ureaplasma species in male infertility and the efficacy of antibiotics in treatment of this failure is not yet definitely determined. A total of 165 infertile males having abnormal semen parameters (study group) as well as 165 healthy fertile men (control group) were included in this study. Semen samples were taken from all participants and after analyzing, undergone real-time PCR, microbial culture, and reactive oxygen species (ROS) as well as total antioxidant capacity (TAC) assays. Infected individuals of study group were treated with antibiotic. One month after the treatment completion, second semen samples were taken and undergone all the tests mentioned. The frequency of Ureaplasma spp. was significantly higher in the infertile men compared with the fertile ones (36.4% versus 11.5%; p < 0.001). Most of semen parameters were improved (p < 0.05) and reached their normal range, the level of TAC elevated (p < 0.001), and ROS level (p = 0.003) as well as ROS/TAC ratio (p = 0.003) reduced after antibiotic treatment. Moreover, wives of 37 infertile men (61.7%) became pregnant six months after the treatment completion. These findings indicate that Ureaplasma species are correlated with male infertility and that antibiotic therapy can improve the semen parameters and treat the male infertility.

Because of biological rhythms, drug efficiency and toxicity vary according to the time of administration of the drug. This study investigates whether the haematological toxicity of the immunosuppressive agent Mycophenolate Mofetil varies according to the circadian dosing-time in rats. 300 mg/kg of Mycophenolate Mofetil was injected by i.p. route to different groups of animals at six different circadian stages (1, 7, 13, and 19 hours after light onset, i.e., HALO). Mycophenolate Mofetil treatment induced a significant decrease at 7 HALO in red blood cells (-18%), in haemoglobin rate (-15%) and in white blood cells (-54%). These parameters followed a circadian rhythm with an acrophase located at the end of the light-rest phase. A significant thrombocytopenia was observed according to Mycophenolate Mofetil the circadian dosing-time. In the controls, the number of platelets followed a circadian rhythm. Mycophenolate Mofetil modified this rhythm which became an 8-h ultradian rhythm. The data indicate that, the Mycophenolate Mofetil-induced haematological toxicity was maximum when the drug was administered in the middle of the light-rest phase, which is physiologically analogous to the end of the activity of the diurnal phase in human patients.

Oxime K203 is a new compound designed to be used as an acetylcholinesterase reactivator for the treatment of intoxication following exposure to tabun and certain pesticides. After intramuscular administration of a therapeutic (23 mg/kg) dose, the time-course of plasma concentrations of K203 in rats was determined by HPLC. Maximum concentrations were reached between 40 and 60 min (16.5±2.1 μg/ml in 40 min and 16.6±2.0 in 60 min, respectively) with the concentration being relatively constant during this period. There was no significant effect on the plasma concentration of thiobarbituric acid reactive substances (TBARS) during the administration of K203, indicating an absence of oxidative stress. Indeed, administration of K203 led to a significant increase in low molecular weight antioxidants which could tentatively be interpreted as representing a beneficial effect.

NF-κB is activated in a variety of human cancers. However, its role in osteosarcoma (OS) remains unknown. Here, we have elucidated the implication of NF-κB in the oncogenic phenotype of OS tumor cells. We reported that activation of NF-κB was a common event in the human OS. Inhibition of NF-κB using inhibitor Bay 11-7085 repressed proliferation, survival, migration, and invasion but increased apoptosis in 143B and MG63 OS cells, indicating that NF-κB is critically implicated in the oncogenesis of OS. Notably, Bay 11-7085 not only inactivated NF-κB but also reduced the phosphorylation of AKT via its induction of PTEN, suggesting the existence of a novel NF-κB/PTEN/PI3K/AKT axis. In vivo, Bay 11-7085 suppressed tumor growth in the bone by targeting NF-κB and AKT. Interestingly, combined treatment with Bay 11-7085 and the PI3K inhibitor, LY294002, triggered an augmented antitumor effect. Our results demonstrate that NF-κB potentiates the growth and aggressiveness of OS. Pharmacological inhibition of NF-κB represents a promising therapy for the treatment of OS.

Huperzine A (Hup A) is a reversible AChE inhibitor that crosses the blood-brain barrier. It is presently approved for, or is in a course of clinical trials for, the treatment of Alzheimer's disease. This compound has also been successfully tested for the pretreatment of organophosphate poisoning. Organophosphate nerve agents are potent irreversible inhibitors of acetylcholinesterase in the central and also in the peripheral compartment. In this study Hup A in a higher dose (500 μg/kg) was tested as a prophylaxis against a high, mainly centrally acting, nerve agent (soman). According to the results obtained, Hup A in this dosage was not able to protect AChE against soman in both the peripheral and central compartments. The effect of Hup A and soman was found to be additive and all animal subjects died.

Health status is determined by the balance of oxidants and antioxidants which protects healthy cells against the threat of internal and external risk factors. Antioxidants such as ascorbate (vitamin C, ascorbic acid) are of fundamental importance in this respect. Ascorbate neutralizes potential damage caused by cellular oxidative stress which may be the greatest risk of damage to healthy tissue. Cellular oxidative stress is mediated by external factors (e.g. psychological stress, physical exertion, drugs, various diseases, environmental pollution, preservatives, smoking, and alcohol) and internal factors (products of cellular metabolism including reactive oxygen species). When the products of oxidative stress are not sufficiently neutralized, healthy cells are at risk for both mitochondrial and DNA damage. In the short term, cell function may deteriorate, while an increased production of proinflammatory cytokines over time may lead to the development of chronic inflammatory changes and diseases, including cancer. Although pharmaceutical research continues to bring effective chemotherapeutic agents to the market, a limiting factor is often the normal tissue and organ toxicity of these substances, which leads to oxidative stress on healthy tissue. There is increasing interest and imperative to protect healthy tissues from the negative effects of radio-chemotherapeutic treatment. The action of ascorbate against the development of oxidative stress may justify its use not only in the prevention of carcinogenesis, but as a part of supportive or complementary therapy during treatment. Ascorbate (particularly when administered parentally at high doses) may have antioxidant effects that work to protect healthy cells and improve patient tolerability to some toxic radio-chemotherapy regimens. Additionally, ascorbate has demonstrated an immunomodulatory effect by supporting mechanisms essential to anti-tumor immunity. Intravenous administration of gram doses of vitamin C produce high plasma levels immediately, but the levels drop rapidly. Following oral vitamin C administration, plasma levels increase slowly to relatively low values, and then gradually decay. With an oral liposomal formulation, significantly higher levels are attainable than with standard oral formulations. Therefore, oral administration of liposomal vitamin C appears to be an optimal adjunct to intravenous administration. In this review, the basic mechanisms and clinical benefits of ascorbate as an antioxidant that may be useful as complementary therapy to chemotherapeutic regimens will be discussed.

Background: Oral and topical nonsteroidal anti-inflammatory drugs (NSAIDs), analgesics and intra-articular corticosteroid injections are the recommended first line of treatment for knee osteoarthritis (OA); however, they have serious side effects. Platelet-rich plasma (PRP) has been posited as an effective and safer alternative treatment for knee OA. Hitherto, there is only one study comparing the effectiveness of PRP against an NSAID. Aim of the study: The aim of this study was to determine the effectiveness of PRP against celecoxib in the treatment of early knee OA. Methods: 60 patients with knee OA grade II and III were randomly alocated in two groups. Group 1 received one injection of autologous PRP in each affected knee, with a reinjection after 15 days; Group 2 received 200 mg of oral celecoxib each 24 h for a year. Visual Analogue Scale (VAS), total Western Ontario and McMaster Universities Arthritis Index (WOMAC) and WOMAC subscales for pain, stiffness and function were measured at baseline and at 1, 3, 6 and 12 months after the start of the treatment. Results: At the end of the study PRP was significantly better than celecoxib (p < 0.05) in improving VAS (40.40%), total WOMAC (58.95%) and WOMAC subscales of pain (50.60%), stiffness (34.13%) and function (51.90%). Significant differences remained after adjusting for age, sex or knee OA grade II or III. Conclusions: Intra-articular PRP is significantly better than celecoxib in improving pain, function and stiffness in early knee OA. This significant difference is independent of age, sex or knee OA grade II or III.

Aim: This study aimed to investigate the phytochemical composition of Psychotria montana extract (PME) and evaluate its inhibitory effects on MCF7 breast cancer cells. Methods: The chemical composition of PME was analyzed using UPLC-QToF-MS. The effects of PME on cell proliferation were evaluated using the MTT assay. Flow cytometry was used for cell cycle and apoptosis analysis. The effects of PME on the transcription of cell cycle control genes were assessed using real-time PCR. Results: UPLC-QToF-MS analysis revealed major compounds of PME, including terpenoids and flavonoids, with the potential to inhibit proliferation, migration, and induce apoptosis in MCF7 cancer cells. PME effectively suppressed MCF7 cell proliferation under 2D culture, with a low IC50 value of 34.7 µg/ml. PME also hindered cell migration (p < 0.01) and reduced spheroid number (p < 0.001) and size (p < 0.001) in serum-free 3D culture. Apoptosis analysis via nuclear staining with DAPI and flow cytometry revealed an increase in the number of apoptotic cells after PME treatment (p < 0.001). Additionally, the PME induced cell cycle arrest at the G0/G1 phase (p < 0.05). PME altered the expression of cell cycle control genes (cyclins and CDKs) as well as cancer suppressor genes including p16, p27, and p53 at the transcriptional level (mRNA). The results of molecular docking suggest that the compounds present in PME exhibit a high binding affinity for CDK3, CDK4, CDK6, and CDK8 proteins, which are essential regulators of the cell cycle. Conclusion: Psychotria montana has the potential to inhibit cancer cells by inducing apoptosis and halting the cell cycle of MCF7 breast cancer cells

Introduction: Tonsil-related procedures are considered fundamental and effective in the surgical treatment of obstructive sleep apnea (OSA). The range of techniques includes intratonsillar approaches, such as tonsillotomy (TT), as well as extracapsular procedures, such as tonsillectomy (TE) and uvulopalatopharyngoplasty (UPPP). Patients undergoing these procedures span all age groups, from children to seniors. Methods: This multicentric retrospective study, conducted between 2014 and 2018, analysed data from 3,498 patients who underwent bilateral TT, TE, or UPPP for OSA or ronchopathy. The cohort included 2,221 men (63.49%) and 1,277 women (36.51%). Of these, 2,808 patients (80.27%) underwent TT, 226 (6.46%) underwent TE, and 464 (13.26%) underwent UPPP. Results: Late postoperative haemorrhage (LPOH) occurrence was significantly associated with the type of surgery (p < 0.0001) and the hospital where the procedure was performed (p < 0.0001). The incidence of LPOH in the TT group ranged from 0% to 5.88% across hospitals (p = 0.0068); whereas in the TE and UPPP groups, rates ranged from 0% to 33.33% (p = 0.0413 and p = 0.0409, respectively). The occurrence of repetitive bleeding was not influenced by treatment choice (readmission vs. outpatient care, observation vs. surgical revision, general vs. local anaesthesia). The severity of bleeding in all three groups was not affected by age and gender. The use of anticoagulants negatively impacted LPOH severity (p = 0.0166) in the UPPP group. No deaths occurred in our sample; however, three cases of severe postoperative bleeding (grade "D") were observed. Conclusion: Late postoperative haemorrhage remains a serious complication of tonsil-related surgery with the potential for life-threatening outcomes. The marked variability in bleeding incidence between surgical techniques and departments highlights the need for standardised perioperative protocols. Although no fatalities occurred, the occurrence of severe cases underlines the importance of vigilant postoperative monitoring. In our OSA cohort, tonsillotomy showed favourable safety, and recent evidence suggests it may represent a valuable alternative also in recurrent tonsillitis, warranting further research.

Takayasu disease belongs to the group of autoimmune vasculitis which most often affects the aorta and its branches. It is rare, and it mainly affects young women. Recent epidemiologic studies suggest that Takayasu arteritis is being increasingly recognized in Europe. The first symptoms are non-specific and an early diagnosis is difficult and requires clinical awareness and suspicion. Patients with Takayasu arteritis often present increased inflammatory markers, including C-reactive protein and erythrocyte sedimentation rate, but systemic inflammatory response does not always show a positive correlation with inflammatory activity in the vessel wall. Therefore, imaging studies play a principal role in diagnosis and control of the disease. Glucocorticoids remain the most effective and serve as a cornerstone first line treatment. Immunosuppressive drugs play an important role as well, and biological therapy is increasingly being included in the treatment. This article describes the epidemiology, pathophysiology, diagnostics and treatment of this rare disease, so as to alert clinicians because disease left untreated can lead to narrowing and even closure of vital blood vessels. The most common Takayasu arteritis complications include pulmonary thrombosis, aortic regurgitation, congestive heart failure, cerebrovascular events, vision degeneration or blindness, and hearing problems.

The potency of three nerve agents (sarin, soman, tabun) to induce oxidative damage of DNA in lymphocytes, liver and brain during lethal or sublethal poisoning was investigated. The single strand breaks or oxidative base DNA damage was evaluated with the help of Comet assay and a specific enzyme able to detect oxidative bases of DNA (endonuclease III). While sarin and soman administered at sublethal doses corresponding to 50% of their LD50 values were not able to induce oxidative damage of DNA, their lethal dose (LD50) induced the significant increase of the number of oxidative bases in DNA of hepatocytes. In addition, tabun administered at lethal dose (LD50) induced significant increase of the number of single strand breaks and oxidative bases of DNA in glial cells isolated from pontomedullar brain region. Thus, some nerve agents were able to induce oxidative damage in the peripheral as well as central compartment but only in the case of severe poisoning caused by lethal doses of nerve agents. This non-cholinergic effect of nerve agents has probably consequences with nerve agents-induced hypoxic status during acute cholinergic crisis and it can contribute to their long-term toxic effects.

Myo-inositol (MI), present in a variety of foods, is essential in several important processes of cell physiology. In this study, we explored the protective effects of MI against hyperglycemia and dyslipidemia in db/db mice, a typical animal model of type 2 diabetes mellitus (T2DM). MI supplement effectively suppressed the high plasma glucose and insulin levels and markedly relieved the insulin resistance (IR) in the db/db mice, comparable to metformin's effects. In MIN6 pancreatic β cells, MI also restrained the upsurge of insulin secretion stimulated by high-concentration glucose but had no impact on the promoted cell proliferation. Moreover, MI abated the enhanced plasma triglyceride and total cholesterol levels in the db/db mice. Notably, the lipid droplet formation of mesenchymal stem cells (MSCs) from db/db mice was significantly diminished after the treatment of MI, indicating that MI could effectively inhibit the differentiation of db/db mouse MSCs into adipocytes. However, MI regretfully failed to control obesity in db/db mice. This work proved that MI significantly helped db/db mice's metabolic disorders, indicating that MI has potential as an effective adjunctive treatment for hyperglycemia and dyslipidemia in T2DM patients.

Diffuse large B-cell lymphoma (DLBCL) stands out as the most common type of malignant cancer, representing the majority of cases of non-Hodgkin's lymphoma. Ethyl pyruvate (EP) is a derivative of pyruvic acid and found to have potent anti-tumor properties. Despite its potential benefits, the impact of EP on DLBCL remains ambiguous. Our objective is to elucidate the role of EP in modulating the development of DLBCL. Analysis of cholecystokinin-8 (CCK-8) revealed that treatment with EP significantly diminished the viability of DLBCL cells. Furthermore, EP administration suppressed colony formation and hindered cell adhesion and invasion in DLBCL cells. Examination of cell cycle progression showed that EP treatment induced arrest at the G1 phase and subsequently reduced the S phase population in DLBCL cells. EP treatment consistently exhibited apoptosis-inducing properties in Annexin-V assays, and notably downregulated the expression of Bcl-2 while increasing levels of proapoptotic cleaved caspase 3 and BAX in DLBCL cells. Additionally, EP treatment decreased the overexpression of c-Jun in c-Jun-transfected DLBCL cells. Further, EP demonstrated DNA-damaging effects in TUNEL assays. In vivo, xenograft animal models revealed that EP treatment significantly mitigated DLBCL tumor growth and suppressed DLBCL cell adhesion to bone marrow stromal cells. In summary, these findings suggest that EP mitigates DLBCL progression by inducing apoptosis, inducing cell cycle arrest, and promoting DNA damage.

Resveratrol (RSV) is a polyphenol antioxidant that has been shown to have neuroprotective effects. We sought molecular mechanisms that emphasize the anti-inflammatory activity of RSV in traumatic brain injury (TBI) in mice associated with endoplasmic reticulum stress (ERS). After establishing three experimental groups (sham, TBI, and TBI+RSV), we explored the results of RSV after TBI on ERS and caspase-12 apoptotic pathways. The expression levels of C/EBP homologous protein (CHOP), glucose regulated protein 78kD (GRP78), caspase-3, and caspase-12 in cortical brain tissues were assessed by western blotting. The qPCR analysis was also performed on mRNA expression of tumor necrosis factor (TNF)-α and interleukin (IL)-1β in cortical brain tissue. In addition, the expression of GRP78 in microglia (ionized calcium binding adaptor molecule 1; Iba-1) and neurons (neuronal nuclei; NeuN) was identified by immunofluorescence staining. The neurological function of mice was assessed by modified neurological severity scores (mNSS). After drug treatment, the expression of CHOP, GRP78, caspase-3 and caspase-12 decreased, and qPCR results showed that TNF-α and IL-1β were down-regulated. Immunofluorescence staining showed down-regulation of Iba-1+/GRP78+ and NeuN+/GRP78+ cells after RSV treatment. The mNSS analysis confirmed improvement after RSV treatment. RSV improved apoptosis by downregulating the ERS signaling pathway and improved neurological prognosis in mice with TBI.

Purpose: The aim of this study was to investigate whether luteoloside, a flavonoid, could protect human dental pulp cells (HDPCs) against inflammation and oxidative stress induced by methylglyoxal (MGO), one of the advanced glycated end products (AGE) substances. Methods: HDPCs were stimulated with MGO and treated with luteoloside. MTT assay was used to determine cell viability. Protein expression was measured via western blotting. Reactive oxygen species (ROS) were measured with a Muse Cell Analyzer. Alkaline phosphatase activity (ALP) and Alizarin red staining were used for mineralization assay. Results: Luteoloside down-regulated the expression of inflammatory molecules such as ICAM-1, VCAM-1, TNF-α, IL-1β, MMP-2, MMP-9, and COX-2 in MGO-induced HDPCs without showing any cytotoxicity. It attenuated ROS formation and enhanced osteogenic differentiation such as ALP activity and Alizarin red staining in MGO-induced HDPCs. Overall, luteoloside showed protective actions against inflammation and oxidative stress in HDPCs induced by MGO through its anti-inflammatory, anti-oxidative, and osteogenic activities by down-regulating p-JNK in the MAPK pathway. Conclusion: These results suggest that luteoloside might be a potential adjunctive therapeutic agent for treating pulpal pathological conditions in patients with diabetes mellitus.

Background: COVID-19 is a viral disease notorious for frequent worldwide outbreaks. It is difficult to control, thereby resulting in overload of the healthcare system. A possible solution to prevent overcrowding is rapid triage of patients, which makes it possible to focus care on the high-risk patients and minimize the impact of crowding on patient prognosis. Methods: The triage algorithm assessed self-sufficiency, oximetry, systolic blood pressure, and the Glasgow coma scale. Compliance with the triage protocol was defined as fulfillment of all protocol steps, including assignment of the correct level of care. Triage was considered successful if there was no change in the scope of care (e.g., unscheduled hospital admission, transfer to different level of care) or if there was unexpected death within 48 hours. Results: A total of 929 patients were enrolled in the study. Triage criteria were fulfilled in 825 (88.8%) patients. Within 48 hours, unscheduled hospital admission, transfer to different level of care, or unexpected death occurred in 56 (6.0%), 6 (0.6%), and 5 (0.5%) patients, respectively. The risk of unscheduled hospital admission or transfer to different level of care was significantly increased if triage criteria were not fulfilled [13.1% vs. 76.1%, RR 5.8 (3.8-8.3), p < 0.001; 0.5% vs. 5.2%, RR 11.4 (2.3-57.7), p = 0.036, respectively]. Conclusion: The proposed algorithm for triage of patients with proven COVID-19 is a simple, fast, and reliable tool for rapid sorting for outpatient treatment, hospitalization on a standard ward, or assignment to an intensive care unit.

Cell senescence is intensively related to aging and neurodegenerative diseases. This study aimed to explore the effect and targets of Astragaloside IV against amyloid-beta-induced astrocyte senescence. Oligomerized amyloid-beta was prepared to culture with human astrocytes. The effects of Astragaloside IV were assessed based on SA-β-gal staining analysis, senescence markers (p53, p16INK4, and p21WAF1), neurotrophic growth factor levels (qRT-PCR), and cell proliferation (CCK-8 kit). The targets for Astragaloside IV were predicted, and hsp90aa1 protein was verified using molecular docking. After hsp90aa1 overexpression, the effects of Astragaloside IV on amyloid-beta-induced astrocytes were assessed. Treatment of human amyloid-beta-induced astrocytes with Astragaloside IV can decrease the percentage of SA-β-gal positive cells, downregulate the p53, p16INK4, and p21WAF1 levels, and increase the levels of neurotrophic growth factors (IGF-1 and NGF mRNA) and cell proliferation. Based on target prediction, hsp90aa1 was found to be a potential target of Astragaloside IV. Moreover, cellular experiments demonstrated that exogenously enhanced expression of hsp90aa1 overexpression suppressed the protective effect of Astragaloside IV on amyloid-beta-induced human astrocytes. The results presented here demonstrate that Astragaloside IV could confront amyloid-beta-induced astrocyte senescence via hsp90aa1, possibly opening new therapeutic avenues.

Acute lymphoblastic leukemia (ALL) is the most common childhood hematological malignancy, but it also affects adult patients with worse prognosis and outcomes. Leukemic cells benefit from protective mechanisms, which are mediated by intercellular signaling molecules - cytokines. Through these signals, cytokines modulate the biology of leukemic cells and their surroundings, enhancing the proliferation, survival, and chemoresistance of the disease. This ultimately leads to disease progression, refractoriness, and relapse, decreasing the chances of curability and overall survival of the patients. Targeting and modulating these pathological processes without affecting the healthy physiology is desirable, offering more possibilities for the treatment of ALL patients, which still remains unsatisfactory in certain cases. In this review, we comprehensively analyze the existing literature and ongoing trials regarding the role of chemokines and interleukins in the biology of ALL. Focusing on the functional pathways, genetic background, and critical checkpoints, we constructed a summary of molecules that are promising for prognostic stratification and mainly therapeutic use. Targeted therapy, including chemokine and interleukin pathways, is a new and promising approach to the treatment of cancer. With the expansion of our knowledge, we are able to uncover a spectrum of new potential checkpoints in order to modulate the disease biology. Several cytokine-related targets are advancing toward clinical application, offering the hope of higher disease response rates to treatment.

Linoleic acid (LA), an essential fatty acid, has emerged as a pivotal regulator in disorders associated with inflammation in recent years; however, the underlying mechanisms are still not completely understood. We utilized network pharmacology and experimental methodologies to elucidate the mechanisms underlying the anti-inflammatory effects of LA. Our network pharmacology analysis revealed that LA shares common targets with sepsis. These targets are enriched in various pathways comprising C-type signaling pathway, PI3K-Akt signaling pathway, toll-like receptor signaling pathway, neutrophil extracellular trap formation, AMPK signaling pathway, and autophagy-animal. These findings suggest that LA may exert regulatory effects on inflammation and autophagy during sepsis. Subsequently, we established in vivo and ex vivo models of sepsis using lipopolysaccharide (LPS) in experimental study. Treatment with LA reduced lung damage in mice with LPS-induced lung injury, and reduced tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in plasma, bronchoalveolar lavage fluid (BALF), and peritoneal lavage fluid (PLF). LA also decreased the production of TNF-α and IL-6 in RAW264.7 macrophages exposed to LPS. In LPS-induced RAW264.7 macrophages, LA induced an elevation in LC3-II while causing a reduction in p62, which was associated with downregulation of toll-like receptor 4 (TLR4). We utilized 3-methyladenine (3-MA) to inhibit the autophagic activity, which reversed the modulatory effects of LA on LC3-II and p62. 3-MA also prevented the decline in TLR4 expression along with reduction in pro-inflammatory cytokines secretion. Our findings suggest that the activation of autophagy by LA may lead to the downregulation of TLR4, thereby exerting its anti-inflammatory effects.

Background: Acanthopanax senticosus (Rupr. et Maxim.) is commonly used in Traditional Chinese Medicine. Syringin is a major ingredient of phenolic glycoside in Acanthopanax senticosus. Objective: This study was performed to investigate whether Syringin could protect high glucose-induced bone marrow mesenchymal stem cells (BMSCs) injury, cell senescence, and osteoporosis by inhibiting JAK2/STAT3 signaling. Methods: BMSCs isolated from both the tibia and femur of mice were induced for osteogenesis. The cell senescence was induced using the high glucose medium. The cells were treated with 10 and 100 μmol/l Syringin. Immunohistochemistry staining was performed to determine the β-galactosidase (SA-β-gal) levels in differentially treated BMSCs. MTT assay and flow cytometry analysis were also performed to assess cell viability and cell cycle. The level of ROS in cells with different treatment was measured by using flow cytometry with DCF-DA staining. Calcium deposition and mineralized matrices were detected with alizarin red and ALP staining, respectively. Osteogenesis related genes OCN, ALP, Runx2, and BMP-2 were detected by RT-PCR. Levels of senescence-related proteins including p53 and p21, as well as JAK2, p-JAK2, STAT3, and p-STAT3 were detected by Western blot analysis. Results: Syringin treatment reversed the phenotypes of senescence caused by high glucose in BMSCs, including the arrest of G0/G1 cell cycle, enhanced SA-β-gal activity, and impaired cell growth. Syringin also decreased the elevated ROS production and the levels of p53, p21, and JAK2/STAT3 signaling activation. In addition, Syringin also enhanced the osteogenic potential determined by ARS and ALP staining, as well as increasing OCN, ALP, Runx2, and BMP-2 expressions. Conclusion: Syringin protects high glucose-induced BMSC injury, cell senescence, and osteoporosis by inhibiting JAK2/STAT3 signaling.