Dysfunctional cardiac energy transduction, mitochondrial oxidative stress, oncogenic and apoptotic signaling in DiNP-induced asthma in murine model.

Diisononyl phthalate (DiNP) has been associated with the development of allergies, asthma, and allergic airway inflammation. Through a complex interplay of signals and feedback mechanisms, the lungs communicate with the heart to ensure maintenance of homeostasis and supporting the body's metabolic demands. In the current study, we assessed the crosstalk between DiNP-induced asthma and cardiac cellular respiration, oxidative stress, apoptotic potential, and induction of oncogenic factors. Ten male BALB/c mice with a weight range of 20-30 g were divided into two groups, each comprising five mice. Group 1 (control), was administered saline orally for a duration of 30 days. In contrast, group 2 (DiNP group), received 50 mg/kg of DiNP to induce asthma. After the final administration and asthma induction, the mice were euthanized, and their hearts were excised, processed, and subjected to biochemical analyses. The DiNP group had downregulated (P < 0.05) activities of the enzymes of glycolysis, tricyclic acid cycle, and electron transport chain except the hexokinase and succinate dehydrogenase activity which were upregulate relative to control. Also, oxidative distress markers (GSH, CAT, and MDA and SOD) were also perturbed. Biomarkers of inflammation (MPO and NO) were considerably higher (P < 0.05) in the heart of DiNP-induced asthma mice as compared with the control group. Furthermore, DiNP-induced asthma group has an increased cardiac caspase-3, Bax, c-Myc and K-ras, and p53 while the Bcl2 decreased when compared with control. Overall, the findings indicate that DiNP-induced asthma impairs cardiac functions by induction of key cardiac oncogenes, downregulation of cardiac energy, transduction of enzymes, and promotion of oxidative stress and cellular death.

Piperacillin/Tazobactam Use vs Cefepime May Be Associated With Acute Decompensated Heart Failure.

Background: Piperacillin/tazobactam (PTZ) has been cautiously used or avoided in patients with a history of heart disease due to concern for heart failure (HF) exacerbation given its relatively high sodium content. However, no prior studies have established this association. Methods: The Antimicrobial Stewardship Team at the James H. Quillen Veterans Affairs Medical Center reviewed the use of PTZ vs the comparator antibiotic, cefepime, in 2 consecutive years to determine whether the use of PTZ was more likely to be associated with acute decompensation of HF. Records of 389 veterans hospitalized in 2018 and 2019 were reviewed and included in this study. Results: Acute decompensation of HF was significantly associated with the use of PTZ (n = 25; 12.3%) compared with cefepime (n = 4; 2.2%) (P < .001). Additionally, hospital readmissions due to HF were higher in the PTZ group compared with the cefepime group (11 vs 1, P = .02). There were no significant differences identified in the length of stay or overall mortality between 204 patients who received PTZ compared with 185 patients who received cefepime (P = .54 and P = .63, respectively). Conclusions: PTZ use was significantly associated with a higher incidence of acute decompensation of HF and hospital readmission with HF exacerbation compared with cefepime. PTZ use among hospitalized patients with a history of HF should be carefully monitored or avoided.

Assessment of genetic homogeneity of in-vitro propagated apple root stock MM 104 using ISSR and SCoT primers.

Apple is an important fruit crop that is always in demand due to its commercial and nutraceutical value. Also, the requirement for quality planting material for this fruit crop for new plantations is increasing continuously. In-vitro propagation is an alternative approach, which may help to produce genetically identical high grade planting material. In this study, for the first time, an efficient and reproducible propagation protocol has been established for apple root stock MM 104 via axillary bud. Culturing axillary buds on Murashige and Skoog apple rootstock (MM 104) resulted in better in-vitro propagation. (MS) basal medium supplemented with 3.0% (w/v) sucrose and 0.8% (w/v) agar. The axillary buds were established in MS basal medium with BA (5.0 µM), NAA (1.0 µM) and further used to establish invitro propagation protocol. Plant Growth Regulators (PGRs), BA (1.0 µM) in combination with NAA (1.0 µM) was found most efficient for shoot multiplication (100%) and produced 9.8 shoots/explants with an average shoot length of (2.4 ± cm). All the shoots produced roots in 0.1 µM IBA with a 5-day dark period. Acclimatization of in-vitro raised plantlets was obtained with vermiculite: perlite: sand: soil (2:2:1:1) resulting in 76% survival under field conditions. The study showed that the use of axillary bud is efficient for multiple-shoot production of apple rootstock (MM 104). This is the first comprehensive report on in-vitro growth of apple root stock MM 104 with an assessment of genetic stability using DNA fingerprinting profiles based on Inter Simple Sequence Repeats (ISSR) and Start Codon Targeted (SCoT). The genetic stability of in-vitro-produced plants, as determined by SCoT and ISSR primers, demonstrated genetic closeness to the mother plant.

Utilizing the drug repurposing strategy on current drugs: new leads for peptic ulcers via biochemical and biomolecular dynamics studies.

The hyperactivity of urease enzymes plays a crucial role in the development of hepatic coma, hepatic encephalopathy, urolithiasis, gastric and peptic ulcers. Additionally, these enzymes adversely impact the soil's nitrogen efficiency for crop production. In the current study 100 known drugs were tested against Jack Bean urease and Proteus mirabilis urease and identified three inhibitors i.e. terbutaline (compound 1), Ketoprofen (compound 2) and norepinephrine bitartrate (compound 3). As a result, these compounds showed excellent inhibition against Jack Bean urease i.e. (IC50 = 2.1-11.3 µM), and Proteus mirabilis urease (4.8-11.9 µM). Moreover, in silico studies demonstrate maximum interactions of compounds in the enzyme's active site. Furthermore, intermolecular interactions between compounds and enzyme atoms were examined using STD-NMR spectrophotometry. In parallel, molecular dynamics simulation was carried out to study compounds dynamic behavior within the urease binding region. Urease remained stable during most of the simulation time and ligands were bound in the protein active pocket as observed from the Root mean square deviation (RMSD) and ligand RMSD analyses. Furthermore, these compounds display interactions with the crucial residues, including His492 and Asp633, in 100 ns simulations. In the binding energy analysis, norepinephrine bitartrate exhibited the highest binding energy (-76.32 kcal/mol) followed by Ketoprofen (-65.56 kcal/mol) and terbutaline (-62.15 kcal/mol), as compared to acetohydroxamic acid (-52.86 kcal/mol). The current findings highlight the potential of drug repurposing as an effective approach for identifying novel anti-urease compounds.Communicated by Ramaswamy H. Sarma.

Immunological interactions in helminths-SARS CoV-2 coinfection: Could old enemy be a friend today?

Helminths are metazoan parasites affecting about one third of the worldwide population. Chronic helminth infections (CHIs) confer immunological tolerance to harmless and self-antigens mediated by regulatory T cells (Treg) that are up-regulated. In coronavirus disease 2019 (COVID-19), abnormal adaptive immune response and unrestrained innate immune response could result in local and systemic immune-mediated tissue damage. COVID-19 and CHIs establish complicated immune interactions due to SARS-CoV-2-induced immunological stimulation and CHIs-induced immunological tolerance. However, COVID-19 severity in patients with CHIs is mild, as immuno-suppressive anti-inflammatory cytokines counterbalance the risk of cytokine storm. Here, an overview of the interplay between helminths and COVID-19 severity is given. CHIs through helminth-derived molecules may suppress SARS-CoV-2 entry and associated hyperinflammation through attenuation of the TLR4/NF-kB signalling pathway. In addition, CHIs may reduce the COVID-19 severity by reducing the SARS-CoV-2 entry points at ACE2/DPP4/CD147 axis in the initial phase and immunomodulation in the late phase of the disease by suppressing TLR4/NF-kB signalling pathway.

Takotsubo cardiomyopathy after microwave ablation of hepatocellular carcinoma.

Takotsubo cardiomyopathy is a form of stress cardiomyopathy that can clinically mimic an acute ST-segment elevation myocardial infarction (STEMI). It involves transient anomalies in left ventricular wall motion secondary to myocardial stunning. Specific causes have still not been elucidated, and several mechanisms have been proposed, including catecholamine surges following intense emotional or physical stress. We present a case of a 74-year-old woman, diagnosed with Takotsubo cardiomyopathy following percutaneous microwave ablation of hepatocellular carcinoma. Although Takotsubo cardiomyopathy comprises a small percentage of acute coronary syndrome presentations, it should be considered in the differential for acute cardiac events as its management varies compared to other more common forms of acute cardiac events.

Catheter-Directed Retrieval of an Infected Fragment in a Vietnam War Veteran.

Background: Shrapnel injuries are commonly encountered in war zones. The severity of these injuries depends on the initial damage and both the anatomical and immune response at the time of injury or at more remote times in the case of reactivation. Case Presentation: A veteran sustained a shrapnel injury to his left lower abdomen while serving in the Vietnam War. Nearly 50 years later, the patient presented with a recurrent retroperitoneal abscess associated with a residual fragment. In cooperation between interventional radiology and surgery, traditional endovascular techniques and devices were used to relocate an extravascular, secondarily infected fragment to an area more suitable for a minor surgical approach in the left inguinal region. Subsequent surgical excision and removal required only a superficial incision as opposed to a large retroperitoneal dissection, minimizing recovery time and allowing quick and full healing of the patient. Conclusions: This case demonstrates a multidisciplinary approach to transforming an otherwise large retroperitoneal dissection to a minimally invasive and technically efficient abscess drainage and foreign body retrieval.

Simple mathematical models for controlling COVID-19 transmission through social distancing and community awareness.

The novel COVID-19 pandemic is a current, major global health threat. Up till now, there is no fully approved pharmacological treatment or a vaccine. Also, its origin is still mysterious. In this study, simple mathematical models were employed to examine the dynamics of transmission and control of COVID-19 taking into consideration social distancing and community awareness. Both situations of homogeneous and nonhomogeneous population were considered. Based on the calculations, a sufficient degree of social distancing based on its reproductive ratio is found to be effective in controlling COVID-19, even in the absence of a vaccine. With a vaccine, social distancing minimizes the sufficient vaccination rate to control the disease. Community awareness also has a great impact in eradicating the virus transmission. The model is simulated on small-world networks and the role of social distancing in controlling the infection is explained.

Coopetition in quantum prisoner's dilemma and COVID-19.

Decision-making is important especially during a crisis such as the novel COVID-19 pandemic. The quantum prisoner's dilemma with two dilemma strength parameters is introduced as a model for the interaction between pharmaceutical and other related enterprises during the pandemic. Novel Nash equilibria are identified. The coopetition equilibrium (simultaneous cooperation and competition) is emphasized. Motivated by the novel equilibria of the quantum version, a classical mixed-strategy formulation that can be applied to real-world situations is proposed. Suitable values of the dilemma strength parameters and quantum entanglement can encourage coopetition, which can be considered as a route to full cooperation.

The modulatory effect of bee honey against diethyl nitrosamine and carbon tetrachloride instigated hepatocellular carcinoma in Wistar rats.

Hepatocellular carcinoma (HCC) is a serious threat to human health that has attracted substantial interest. The purpose of this study was to investigate the modulatory effect of bee honey against induced HCC by diethylnitrosamine/carbon tetrachloride (DEN/CCl4) in rats. HCC was induced by a single intraperitoneal dose of DEN (200 mg/kg B.W). Two weeks later, CCl4 (1 ml/kg) was intraperitoneally injected (three times a week). Bee honey was administered orally at 2 g/rat before and after the induction of HCC. The results showed that bee honey administration significantly increased body weight, decreased liver weight, and relative liver weight compared to those in the HCC-induced group. Moreover, a significant decrease in serum alpha-fetoprotein (AFP) as well as AST, ALT, GGT, ALP activities were observed in bee honey administration rats compared with those in HCC-induced group. Also, the hepatic MDA was significantly decreased; in addition, SOD, CAT, and GPx activities were significantly increased in groups treated with bee honey compared with those in the HCC group. The hepatic histopathology alterations caused by DEN/CCl4 injection were ameliorated by bee honey treatment. Likewise, the mRNA expression levels of tumor necrosis factor-alpha (TNF-α), transforming growth factor (TGF-ß1), intracellular adhesion molecule-1 (ICAM-1), vascular cellular adhesion molecule-1 (VCAM-1), glypican (GP-3), thioredoxin (TRX), and glutaredoxin (GRX) were downregulated, and caspase-3 was upregulated by bee honey treatment compared with untreated HCC-induced group. In conclusion, bee honey has remarkable beneficial effects against HCC induced in rats through its antioxidant, anti-inflammatory, antifibrotic, and antimetastatic effects. PRACTICAL APPLICATIONS: The current study confirmed that honey has the potential to act as an antimetastatic factor. Bee honey supplementation either before or after combined injection of DEN/CCl4 exhibited inhibitory and ameliorative effects against DEN/CCl4-induced HCC through its antioxidant, antiproliferative, anti-metastatic, antifibrotic, and apoptosis properties. To our knowledge, this is the first study to describe the molecular mechanisms underlying honey's effects against DEN/CCl4-induced HCC in rats.

Physical endometrial manipulation and its impact on success rate and live birth rate in ICSI in patients with unexplained infertility after recurrent ICSI failure, a double blinded randomized controlled trial.

Background: Unexplained infertility is a rising problem and endometrial manipulation could be one of the solutions for enhancing the pregnancy rate and live birth rate in such circumstances.Aims: To evaluate the influence of local endometrial physical manipulation with specializd method for endometrial and tubal hydration (Elgazzar and Alalfy technique) on ICSI outcome and in increasing chemical, clinical, and live birth rate in ICSI after previous recurrent ICSI failure in patients with unexplained infertility.Results: When comparing group 1 (hydrotubation group) and group 2 (the control group with no intervention) with regards to the biochemical, clinical, and live birth rate, the hydrotubation group revealed higher rates and a better ICSI outcome.Conclusion: Hydrotubation is useful in increasing biochemical, clinical, and live birth rates after recurrent failed ICSI trials with a specialized method for hydration of endometrium and tubes (Elgazzar and Alalfy technique).

Insight Study on the Comparison between Zinc Oxide Nanoparticles and Its Bulk Impact on Reproductive Performance, Antioxidant Levels, Gene Expression, and Histopathology of Testes in Male Rats.

Background: Despite the beneficial effects of zinc oxide nanoparticles (ZnONPs) on different biomedical applications, including their antioxidant and anti-inflammatory ones, it might have cytotoxic and genotoxic impacts on the male reproductive system. Objective: The current study compares the effect of zinc oxide nanoparticles and their bulk form, at different doses, on male rats' reproductive performance, testicular antioxidants, gene expression, and histopathology. Materials and Methods: Thirty male rats were randomly allocated equally in five groups. The control one was injected with Tween 80 (10%). The zinc oxide nanoparticle (ZnONP) groups received ZnONPs < 50 nm, specifically, 5 mg/kg (ZnONP-1) and 10 mg/kg (ZnONP-2). The bulk zinc oxide (BZnO) groups were administered 5 mg/kg (BZnO-1) and 10 mg/kg (BZnO-2), correspondingly. Rats were injected intraperitoneally with the respected materials, twice/week for eight consecutive weeks. Finally, the male rats' sexual behavior and their pup's performance were determined in a monogamous mating system. Rats were then anesthetized and sacrificed for semen characteristics evaluation and tissue collection for antioxidant and hormones analysis, gene expression, and histopathological examination. Results: It was shown that ZnONP-1 improved sexual behavior, semen characteristics, and pup's performance compared to its bulk form. Similarly, the testicular antioxidants activity, glutathione (GSH), and superoxide dismutase (SOD) increased with a decrease in the malonaldehyde (MDA), interleukin 6 (IL-6), and tumor necrosis factor (TNF-α) levels. It also improves the reproductive hormone levels and mRNA expression of different steroidogenesis-associated genes and anti-apoptotic genes. Conclusion: It can be concluded that zinc oxide nanoparticles, administered at 5 mg/kg, had the most beneficial effect on male reproductive performance, while 10 mg/kg could have a detrimental effect.

Effect of subcutaneous tissue closure technique in cesarean section on postoperative wound complications in obese Egyptian women.

Subcutaneous tissue closure technique is a wide area of interest for obstetricians who perform cesarean section especially on obese women while many observers studied in an extensive manner postoperative pain and wound cosmetic results. AIM OF THE WORK: The main goal of our work was to display the differences in wound outcome results as regard postoperative wound complications comparing the two widely implemented techniques in subcutaneous tissue closure (interrupted versus continuous methods). RESULTS: A comparative analysis between continuous and interrupted techniques regarding wound complications (gapping, seroma, erythema, and infection) showing statistical significant differences in all four wound complications presented with p values = .019, .011, .015, and .001, in consecutive order with odds ratio in wound gapping = 5.239, wound seroma OR = 9.429, wound erythema OR = 3.709, and wound infection OR = 6.136. CONCLUSIONS: Subcutaneous wound closure using interrupted technique of suturing in obese patients is superior to continuous technique as regard wound complications. Clinical trials.gov ID Identifier (NCT03354078).