Histopathological effects of the fruit extract of Citrullus colocynthis on the ovary of the tick Hyalomma dromedarii.

Hyalomma dromedarii is the predominant tick species parasitizing camels in Egypt which leads to mortalities in young animals that result in economic losses. It can transmit a lot of pathogens to animals and humans, such as the Crimean-Congo hemorrhagic fever virus, the Dhori virus, Kadam virus, Theileria annulata and spotted fever rickettsia. The continuous use of chemical acaricides has negative impact on the environment and almost led to acaricidal resistance, and hence the plant extracts represent alternative methods for controlling ticks. The present study was carried out to assess the histopathological effects on the ovary of fed female Hyalomma dromedarii following immersion in the ethanolic extract of fruits of Citrullus colocynthis (100 mg/mL). Light, scanning and transmission electron microscopy observations provided evidence that Citrullus colocynthis caused extensive damage to oocytes. Destruction of the internal organelles of oocytes, along with delay and/or inhibition of vitellogenesis were demonstrated. This is the first histological study that points to damage in H. dromedarii ovaries following treatment with the ethanolic extract of fruits of C. colocynthis. The data presented suggest that the plant extract affects the ovary either directly by entering the oocytes and/or indirectly by damaging the gut cells and digestion of blood that interfere with the development of oocytes, so it can be used as a promising agent for tick control.

The renoprotective activity of amikacin-gamma-amino butyric acid-chitosan nanoparticles: a comparative study.

The development of nanoparticles (NPs) with active components with upgraded stability, and prolonged release helps in enhanced tissue regeneration. In addition, NPs are feasible strategy to boost antibiotic effectiveness and reduce drug side effects. Our study focuses on the use of amikacin (AMK) and gamma amino butyric acid (GABA) unloaded combinations or loaded on chitosan nanoparticles (CSNPs) for kidney protection. The AMK-GABA-CSNPs were prepared with the ionic gelation method, the morphology was studied using transmission electron microscopy (TEM), zetasizer and the Fourier transform-infrared spectroscopy (FT-IR) spectrum of the synthesized NPs was observed. The average size of AMK-GABA-CSNPs was 77.5 ± 16.5 nm. Zeta potential was + 38.94 ± 2.65 mV. AMK-GABA-CSNPs revealed significant in vitro antioxidant, anti-coagulation, non-hemolytic properties and good cell compatibility. To compare the effects of the unloaded AMK-GABA combination and AMK-GABA-CSNPs on the renal tissue, 42 healthy Sprague-Dawley rats were divided into seven groups. G1: normal control (NC), normal saline; G2: low-dose nephrotoxic group (LDN), AMK (20 mg/kg/day; i.p.); G3: unloaded AMK (20 mg/kg/day; i.p.) and GABA (50 mg/kg/day; i.p.); G4: AMK-GABA-CSNPs (20 mg/kg/day; i.p.); G5: high-dose nephrotoxic group (HDN), AMK (30 mg/kg/day; i.p.); G6: unloaded AMK (30 mg/kg/day; i.p.) and GABA (50 mg/kg/day; i.p.) and G7: AMK-GABA-CSNPs (30 mg/kg/day; i.p.). The results showed that AMK-GABA-CSNPs formulation is superior to unloaded AMK-GABA combination as it ameliorated kidney functions, oxidative stress and displayed a significant homeostatic role via suppression of inflammatory cytokines of Th1, Th2 and Th17 types. Hence, AMK-GABA-CSNPs could afford a potential nano-based therapeutic formula for the management of AMK-nephrotoxicity.

Eobania vermiculata whole-body muscle extract-loaded chitosan nanoparticles enhanced skin regeneration and decreased pro-inflammatory cytokines in vivo.

BACKGROUND: Usually, wounds recover in four to six weeks. Wounds that take longer time than this to heal are referred to as chronic wounds. Impaired healing can be caused by several circumstances like hypoxia, microbial colonization, deficiency of blood flow, reperfusion damage, abnormal cellular reaction and deficiencies in collagen production. Treatment of wounds can be enhanced through systemic injection of the antibacterial drugs and/or other topical applications of medications. However, there are a number of disadvantages to these techniques, including the limited or insufficient medication penetration into the underlying skin tissue and the development of bacterial resistance with repeated antibiotic treatment. One of the more recent treatment options may involve using nanotherapeutics in combination with naturally occurring biological components, such as snail extracts (SE). In this investigation, chitosan nanoparticles (CS NPs) were loaded with an Eobania vermiculata whole-body muscle extract. The safety of the synthesized NPs was investigated in vitro to determine if these NPs might be utilized to treat full-skin induced wounds in vivo. RESULTS: SEM and TEM images showed uniformly distributed, spherical, smooth prepared CS NPs and snail extract-loaded chitosan nanoparticles (SE-CS NPs) with size ranges of 76-81 and 91-95 nm, respectively. The zeta potential of the synthesized SE-CS NPs was - 24.5 mV, while that of the CS NPs was 25 mV. SE-CS NPs showed a remarkable, in vitro, antioxidant, anti-inflammatory and antimicrobial activities. Successfully, SE-CS NPs (50 mg/kg) reduced the oxidative stress marker (malondialdehyde), reduced inflammation, increased the levels of the antioxidant enzymes (superoxide dismutase and glutathione), and assisted the healing of induced wounds. SE-CS NPs (50 mg/kg) can be recommended to treat induced wounds safely. SE was composed of a collection of several wound healing bioactive components [fatty acids, amino acids, minerals and vitamins) that were loaded on CS NPs. CONCLUSIONS: The nanostructure enabled bioactive SE components to pass through cell membranes and exhibit their antioxidant and anti-inflammatory actions, accelerating the healing process of wounds. Finally, it is advised to treat rats' wounds with SE-CS NPs.

Biological evaluation, docking studies, and in silico ADME prediction of some pyrimidine and pyridine derivatives as potential EGFRWT and EGFRT790M inhibitors.

Herein, a set of pyridine and pyrimidine derivatives were assessed for their impact on the cell cycle and apoptosis. Human breast cancer (MCF7), hepatocellular carcinoma (HEPG2), larynx cancer (HEP2), lung cancer (H460), colon cancers (HCT116 and Caco2), and hypopharyngeal cancer (FADU), and normal Vero cell lines were used. Compounds 8 and 14 displayed outstanding effects on the investigated cell lines and were further tested for their antioxidant activity in MCF7, H460, FADU, HEP2, HEPG2, HCT116, Caco2, and Vero cells by measuring superoxide dismutase (SOD), malondialdehyde content (MDA), reduced glutathione (GSH), and nitric oxide (NO) content. Besides, Annexin V-FITC apoptosis detection and cell cycle DNA index using the HEPG-2 cell line were established on both compounds as well. Furthermore, compounds 8 and 14 were assessed for their EGFR kinase (Wild and T790M) inhibitory activities, revealing eligible potential. Additionally, molecular docking, ADME, and SAR studies were carried out for the investigated candidates.

Development of Apoptotic-Cell-Inspired Antibody-Drug Conjugate for Effective Immune Modulation.

BACKGROUND: Apoptotic cells' phosphoserine (PS) groups have a significant immunosuppressive effect. They inhibit proinflammatory signals by interacting with various immune cells, including macrophages, dendritic cells, and CD4+ cells. Previously, we synthesized PS-group-immobilized polymers and verified their immunomodulatory effects. Despite its confirmed immunomodulatory potential, the PS group has not been considered as a payload for antibody-drug conjugates (ADCs) in a targeted anti-inflammatory approach. AIM: We conducted this research to introduce an apoptotic-cell-inspired antibody-drug conjugate for effective immunomodulation. METHOD: Poly(2-hydroxyethyl methacrylate-co-2-methacryloyloxyethyl phosphorylserine) (p(HEMA-co-MPS)) was synthesized as a payload using RAFT polymerization, and goat anti-mouse IgG was selected as a model antibody, which was conjugated with the synthesized p(HEMA-co-MPS) via 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide/N-Hydroxysuccinimide (EDC/NHS) reaction. The antibody-binding affinity, anti-inflammatory potential, and cytotoxicity measurements were evaluated. RESULTS: We successfully synthesized ADCs with a significant anti-inflammatory effect and optimized the antibody-polymer ratio to achieve the highest antibody-binding affinity. CONCLUSION: We successfully introduced p(HEMA-co-MPS) to IgG without decreasing the anti-inflammatory potential of the polymer while maintaining its targeting ability. We suggest that the antibody-polymer ratio be appropriately adjusted for effective therapy. In the future, this technology can be applied to therapeutic antibodies, such as Tocilizumab or Abatacept.

The relationship between B-cell lymphoma 2, interleukin-1ß, interleukin-17, and interleukin-33 and the development of diabetic nephropathy.

BACKGROUND: Diabetic nephropathy (DN) is among the main complications of diabetes mellitus and has been a major factor of renal failure. This study was designed to address the association between beta-cell lymphoma-2 (Bcl-2), interleukin (IL)-1ß, IL-17, and IL-33 and the development of DN. METHODS: In this study, 20 healthy volunteers and 100 patients were enrolled. According to their biochemical markers, the patients were categorized into five groups: diabetic, chronic renal disease, diabetic chronic renal disease, end-stage renal disease, and diabetic end-stage renal disease. RESULTS: Our results showed a noticeable elevation in IL-1ß and IL-17 levels and a reduction in IL-33 and Bcl-2 levels in all investigated groups compared with those in the healthy group. Positive correlations were found between IL-1ß and fasting blood sugar and between creatinine levels and IL-17, HbA1c%, and sodium levels. However, negative correlations were found between IL-33 and urea and sodium concentrations and between Bcl-2 and HbA1c% and creatinine levels. CONCLUSIONS: The present data revealed a marked relationship between Bcl-2, IL-1ß, IL-17, and IL-33 levels and the onset and progression of DN. Understanding the molecular pathways of these processes could be translated into the development of therapeutic strategies.

Temperature Responsive Polymer Conjugate Prepared by "Grafting from" Proteins toward the Adsorption and Removal of Uremic Toxin.

In this study, temperature-responsive polymer-protein conjugate was synthesized using a "grafting from" concept by introducing a chain transfer agent (CTA) into bovine serum albumin (BSA). The BSA-CTA was used as a starting point for poly(N-isopropylacrylamide) (PNIPAAm) through reversible addition-fragmentation chain transfer polymerization. The research investigations suggest that the thermally responsive behavior of PNIPAAm was controlled by the monomer ratio to CTA, as well as the amount of CTA introduced to BSA. The study further synthesized the human serum albumin (HSA)-PNIPAAm conjugate, taking the advantage that HSA can specifically adsorb indoxyl sulfate (IS) as a uremic toxin. The HSA-PNIPAAm conjugate could capture IS and decreased the concentration by about 40% by thermal precipitation. It was also revealed that the protein activity was not impaired by the conjugation with PNIPAAm. The proposed strategy is promising in not only removal of uremic toxins but also enrichment of biomarkers for early diagnostic applications.

Isolating the entire pulmonary venous component versus isolating the pulmonary veins for persistent atrial fibrillation: A propensity-matched analysis.

BACKGROUND: The outcomes of pulmonary vein isolation (PVI) for persistent atrial fibrillation (AF) are suboptimal. The entire pulmonary venous component (PV-Comp), consisting of the pulmonary veins, their antra, and the area between the antra, provides triggers and substrate for AF. PV-Comp isolation is an alternative strategy for persistent AF ablation. METHODS: Among 328 patients with persistent AF who underwent a first radiofrequency ablation procedure, 200 patients (PVI, n = 100; PV-Comp isolation, n = 100) were selected by propensity score matching. Both groups were followed up for 1 year. RESULTS: At 6- and 12-month follow-up, atrial tachyarrhythmia (AF/atrial tachycardia) recurred in 41 and 61 patients in PVI group and 22 (P = .006) and 33 patients (P < .001) in PV-Comp isolation group, respectively. PV-Comp isolation was associated with longer mean time to recurrence (PVI: 8 months, PV-Comp isolation: 10 months, log-rank P < .001) and a lower probability of recurrence (odds ratio [OR] = 0.32; 95% confidence of interval [CI] = 0.18-0.56, P < .001), with no increase in procedural complications (PVI: 5 of 100, PV-Comp isolation: 6 of 100, P = .76). Procedure duration was longer in PV-Comp isolation group (PVI: 186 ± 42 min, PV-Comp isolation: 238 ± 44 min, P < .001), as well as fluoroscopy time (PVI: 22 ± 16 min, PV-Comp isolation: 31 ± 21 min, P = .001). CONCLUSION: PV-Comp isolation for persistent AF reduced atrial tachyarrhythmia recurrence up to 1 year compared with PVI alone. While procedure and fluoroscopy time increased, there was no difference in procedural complications.

Prevalence and Risk of Polypharmacy among Community-Dwelling, Elderly Kuwaiti Patients.

OBJECTIVES: To estimate the prevalence of polypharmacy in community-dwelling, older Kuwaiti patients, describe the number and types of drugs used, and identify risk factors associated with polypharmacy. SUBJECTS AND METHODS: This was a descriptive cross-sectional questionnaire-based survey in which we interviewed 500 community-dwelling Kuwaiti adults over 65 years of age. The data collection occurred during a 4-month period from March to July 2017. RESULTS: Fifty-two percent (n = 260) of the patients were males, with a mean age of 71.73 ± 5.32 years. The prevalence of polypharmacy (5-8 drugs) and excessive polypharmacy (>8 drugs) was 58.4% (n = 292) and 10.2% (n = 51), respectively. The risk factors associated with an increased number of medicines used were: female gender (p = 0.019), a lower level of education (p = 0.003), a high number of hospital admissions (p = 0.000), clinics visited by the patient (p =0.000), and number of comorbidities (p = 0.000). The most commonly used medications (82.6% of the study population) were blood glucose-lowering agents, excluding insulin. Other commonly used medications were antihypertensive drugs and lipid-modifying agents. CONCLUSION: A significant sector of the older Kuwaiti patient population has a high prevalence of polypharmacy and is thus exposed to its potential hazards. The current study highlights the need to revise the drug-dispensing policy among community-dwelling, older Kuwaiti people, as well as to initiate educational programs among healthcare practitioners concerning prescribing issues in older individuals.

Genetic diversity in Corchorus olitorius L. revealed by morphophysiological and molecular analyses.

Assessment of genetic diversity has an efficient role in plant breeding and improvement programs. There is a limit number of investigations dealing with the evaluation of genetic diversity in Jew's mallow (Corchorus olitorius L.), despite its valuable importance as a leafy vegetable and a delicious dish rich in vitamins and antioxidants. Therefore, in this study, 18 landraces of Jew's mallow-collected from different locations in Egypt-were used for genetic diversity assessment based on morphophysiological and molecular evaluations. A high degree of variability was found among the evaluated landraces at both levels, indicating the appropriateness of such collection to be involved in breeding approaches. Some morphophysiological traits offered a high level of diversity and effectively discriminated the landraces. Thus, they are recommended to be used in successive morphological evaluation studies. On the other hand, molecular evaluation using the random amplified polymorphic DNA (RAPD) and the sequence related amplified polymorphism (SRAP) efficiently supported the morphological results by exposing a clear genetic relationship among the landraces. In addition, the principal coordinate analysis based on combined data of RAPD and SRAP divided the landraces into two main groups, reflecting their relationship molecularly. The first group included nine landraces related to Upper Egypt and the second gathered three landraces from Delta, while the other six landraces were distinctly distributed around these two groups. The two groups may have two distinct ancestors in addition to the different ancestors of the scattered landraces. Findings of this study are valuable and could assist in Jew's mallow breeding programs.

Vascularized fibular medialization for reconstruction of the tibial defects following tumour excision.

PURPOSE: The purpose of this study was to evaluate the functional and oncologic results of fibular medialization when used alone as a single-stage reconstructive technique after wide excision of malignant tumours of the proximal, middle, or distal tibia. METHODS: Between December 2010 and May 2015, 14 patients (six males and eight females) with primary malignant tumours of the tibia (eight proximal, four diaphyseal, two distal) were treated by wide excision. The mean age of the patients at the time of surgery was 23.2 years (11-38). The fibula was mobilized medially with its vascular pedicle to fill the defect and was fixed by a long plate and screws bypassing the graft. The average size of the defects reconstructed was 19.5 cm (18-22). Patients were evaluated functionally using the Musculoskeletal Tumour Society (MSTS) scoring system. RESULTS: The mean follow-up period was 31.3 months (range, 17-54). The average time for complete union was 7.6 months (range, 6-9). At final follow-up all patients had fully united grafts; 11 walked without aids. Chest metastases developed in one patient, superficial wound infection in two patients and leg length discrepancy in four patients; one case had LLD of more than 3 cm. The mean MSTS score was 23/30 points (76.5%). The minimum score was 40% (12/30) and the maximum was 90% (27/30). CONCLUSIONS: Ipsilateral pedicled vascularized fibular centralisation or medialization is a durable reconstruction for tibial defects after wide excision of bone tumours with an acceptable functional outcome. Stable osteosynthesis is the key to union.

Histological observations of pulpal replacement tissue in immature dog teeth after revascularization of infected pulps.

BACKGROUND AND AIM: Many studies have examined the nature of tissue formed in the canals of immature necrotic teeth, following revascularization in animals and humans. While speculations have been made that regeneration of the pulp tissue might take place in the canal, the tissue has been found to be cementum-like, bone-like, and periodontal ligament-like. The purpose of this study was to histologically examine the tissue in the root canals in immature dog teeth that had been artificially infected and then revascularized. METHODS: Two 4- to 5-month-old mongrel dogs with immature teeth were used in the study. In one dog, four maxillary and four mandibular anterior teeth, and in another dog, four maxillary and five mandibular anterior teeth were used in the experiment. Pulp infection was artificially induced in the immature teeth. Revascularization was performed on all teeth by disinfecting the root canals with sodium hypochlorite irrigation and triple antibiotic intracanal dressing, completed with induction of intracanal bleeding, and sealed with an MTA plug. The access cavity was restored with silver amalgam. The animals were sacrificed 3 months after revascularization procedures. The revascularized teeth and surrounding periodontal tissues were removed and prepared for histological examination. RESULTS: Besides cementum-like, bone-like, and periodontal ligament-like tissues formed in the canals, residual remaining pulp tissue was observed in two revascularized teeth. In four teeth, ingrowth of alveolar bone into the canals was seen; presence of bone in the root canals has the potential for ankylosis. CONCLUSIONS: Within the limitation of this study, it can be concluded that residual pulp tissue can remain in the canals after revascularization procedures of immature teeth with artificially induced pulp infection. This can lead to the misinterpretation that true pulpal regeneration has occurred. Ingrowth of apical bone into the root canals undergoing revascularization can interfere with normal tooth eruption if ankylosis occurs.

A Comparative Study of "Grafting to" and "Grafting from" Conjugation Methods for the Preparation of Antibody-Temperature-Responsive Polymer Conjugates.

Early diagnosis of infectious diseases is still challenging particularly in a nonlaboratory environment or limited resources areas. Thus, sensitive, inexpensive, and easily handled diagnostic approaches are required. The lateral flow immunoassay (LFIA) is commonly used in the screening of infectious diseases despite its poor sensitivity, especially with low pathogenic loads (early stages of infection). This article introduces a novel polymeric material that might help in the enrichment and concentration of pathogens to overcome the LFIA misdiagnosis. To achieve this, we evaluated the efficiency of introducing poly(N-isopropylacrylamide) (PNIPAAm) into immunoglobulin G (IgG) as a model antibody using two different conjugation methods: grafting to (GT) and grafting from (GF). The IgG-PNIPAAm conjugates were characterized using SDS-PAGE, DLS, and temperature-responsive phase transition behavior. SDS-PAGE analysis revealed that the GF method was more efficient in introducing the polymer than the GT method, with calculated polymer introduction ratios of 61% and 34%, respectively. The GF method proved to be less susceptible to steric hindrance and more efficient in introducing high-molecular-weight polymers into proteins. These results are consistent with previous studies comparing the GT and GF methods in similar systems. This study represents an important step toward understanding how the choice of polymer incorporation method affects the properties of IgG-PNIPAAm conjugates. The synthesized polymer allowed binding and enrichment of mouse IgG that was used as a model antigen with a clear LFIA band. On the basis of our findings, this system might help in improving the sensitivity of simple diagnostics.

Does lateral extra-articular tenodesis affect knee stability in cases with isolated anterior cruciate ligament reconstruction?

Objective: The purpose of this randomised controlled trial was to assess the effect on knee function and stabilising effectiveness of lateral extra-articular tenodesis (LET) in anterior cruciate ligament (ACL) restoration. Methods: A prospective randomised clinical study that compared the functional outcomes of two groups-one undergoing anatomic single bundle ACL reconstruction (ASB-ACLR) with ilio-tibial band tenodesis (LET) for 20 patients, and the other undergoing ASB-ACLR-was carried out between February 2020 and August 2022. Results: By combining Lateral Extra-articular Tenodesis (LET) with intra-articular Anterior Cruciate Ligament Reconstruction (ACLR), our study observed a significant reduction in the occurrence of high-grade pivot-shift phenomena. Prior to surgery, both Groups A and B exhibited graded (D) pivot-shift test results. However, post-surgery, the pivot-shift test yielded negative results in 60% of patients in Group A and 90% of patients in Group B. The statistical analysis revealed a notable difference between the two groups, as indicated by a P-value of 0.003. Upon conducting a brief follow-up, we evaluated the Lysholm score, and anterior knee stability of ACLR with LET, finding no statistically significant difference compared to those of single ACLR. The Lachman tests also revealed no significant disparity between the two groups (p = 0.106). Analyzing the Lysholm scores in Group A and Group B, we observed an increase to 90.70% and 91.10%, respectively. Conclusion: Rotational stability is much improved when lateral extra-articular tenodesis (LET) utilizing the ilio-tibial band as an augmentation is used in ACL restoration. Especially useful for high-grade pivot-shift phenomena is this technique.

Evaluation of urea breath test as a diagnostic tool for Helicobacter pylori infection in adult dyspeptic patients.

In this editorial, we discuss the article in the World Journal of Gastroenterology. The article conducts a meta-analysis of the diagnostic accuracy of the urea breath test (UBT), a non-invasive method for detecting Helicobacter pylori (H. pylori) infection in humans. It is based on radionuclide-labeled urea. Various methods, both invasive and non-invasive, are available for diagnosing H. pylori infection, including endoscopy with biopsy, serology for immunoglobulin titers, stool antigen analysis, and UBT. Several guidelines recommend UBTs as the primary choice for diagnosing H. pylori infection and for reexamining after eradication therapy. It is used to be the first choice non-invasive test due to their high accuracy, specificity, rapid results, and simplicity. Moreover, its performance remains unaffected by the distribution of H. pylori in the stomach, allowing a high flow of patients to be tested. Despite its widespread use, the performance characteristics of UBT have been inconsistently described and remain incompletely defined. There are two UBTs available with Food and Drug Administration approval: The 13C and 14C tests. Both tests are affordable and can provide real-time results. Physicians may prefer the 13C test because it is non-radioactive, compared to 14C which uses a radioactive isotope, especially in young children and pregnant women. Although there was heterogeneity among the studies regarding the diagnostic accuracy of both UBTs, 13C-UBT consistently outperforms the 14C-UBT. This makes the 13C-UBT the preferred diagnostic approach. Furthermore, the provided findings of the meta-analysis emphasize the significance of precise considerations when choosing urea dosage, assessment timing, and measurement techniques for both the 13C-UBT and 14C-UBT, to enhance diagnostic precision.

Design of an apoptotic cell-mimetic wound dressing using phosphoserine-chitosan hydrogels.

Inflammatory M1 macrophages create a hostile environment that impedes wound healing. Phosphoserine (PS) is a naturally occurring immunosuppressive molecule capable of polarizing macrophages from an inflammatory phenotype (M1) to an anti-inflammatory phenotype (M2). In this study, we designed, fabricated, and characterized PS-immobilized chitosan hydrogels as potential wound dressing materials. A PS group precursor was synthesized via a phosphoramidite reaction and subsequently immobilized onto the chitosan chain through an EDC/N-hydroxysuccinimide reaction using a crosslink moiety HPA. The PS/HPA-conjugated chitosan (CS-PS) was successfully synthesized by deprotecting the PS group in HCl. In addition, the hydrogels were prepared by the HRP/H2O2 enzyme-catalyzed reaction with different PS group contents (0, 7.27, 44.28 and 56.88 µmol g-1). The immobilization of the PS group improved the hydrophilicity of the hydrogels. Interestingly, CS-PS hydrogel treatment upregulated both pro-inflammatory and anti-inflammatory cytokines. This treatment also resulted in alterations in the macrophage cell morphology from the M1 to M2 phenotype. The CS-PS hydrogel significantly accelerated diabetic wound healing. Overall, this study provides insights into the potential of PS-immobilized hydrogel materials for improved inflammatory disease therapy.

A facile, flexible, and multifunctional thermo-chemotherapy system for customized treatment of drug-resistant breast cancer.

Anticancer drug resistance invariably emerges and poses a significant barrier to curative therapy for various breast cancers. This results in a lack of satisfactory therapeutic medicine for cancer treatment. Herein, a universal vector system for drug-resistance breast cancer was designed to meet the needs of reversed multidrug resistance, thermo-chemotherapy, and long-term drug release behavior. The vector system comprises polycaprolactone (PCL) nanofiber mesh and magnetic nanoparticles (MNPs). PCL has excellent biocompatibility and electrospinning performance. In this study, MNPs were tailored to be thermogenic in response to an alternating magnetic field (AMF). PCL nanofiber can deliver various chemotherapy drugs, and suitable MNPs encapsulated in the nanofiber can generate hyperthermia and synergistic effect with those chemotherapy drugs. Therefore, a more personalized treatment system can be developed for different breast malignancies. In addition, the PCL nanofiber mesh (NFM) enables sustained release of the drugs for up two months, avoiding the burden on patients caused by repeated administration. Through model drugs doxorubicin (DOX) and chemosensitizers curcumin (CUR), we systematically verified the therapeutic effect of DOX-resistance breast cancer and inhibition of tumor generation in vivo. These findings represent a multifaceted platform of importance for validating strategic reversed MDR in pursuit of promoted thermo-chemotherapeutic outcomes. More importantly, the low cost and excellent safety and efficacy of this nanofiber mesh demonstrate that this can be customized multi-function vector system may be a promising candidate for refractory cancer therapy in clinical.

COVID-19-induced transaminitis and hyperbilirubinemia: Presentation and outcomes.

The risk of liver injury in patients with coronavirus disease 2019 (COVID-19) infection is quite evident. Furthermore, liver function test abnormalities are still detected in COVID-19 patients despite the development of antivirals and the availability of several types of vaccines. This editorial describes liver involvement during COVID-19 infection in patients with or without preexisting liver injury, such as chronic liver disease, to elucidate COVID-19-induced liver function abnormalities and their severity, pathophysiology, clinical manifestations, and clinical and laboratory outcomes. We also discuss the effect of vaccination against COVID-19 to better understand host factors, such as age, gender, and race, on the incidence and severity of liver dysfunction at initial presentation and during the illness. Finally, we summarize the results of relevant meta-analyses published to date and highlight the importance of adequate liver function monitoring in the current climate of the overwhelming COVID-19 pandemic.

Silver nanoparticles induced testicular damage targeting NQO1 and APE1 dysregulation, apoptosis via Bax/Bcl-2 pathway, fibrosis via TGF-ß/α-SMA upregulation in rats.

In medicine, silver nanoparticles (AgNPs) are employed often. They do, however, have negative impacts, particularly on the reproductive organs. This research aimed to assess AgNP impact on the testis and the possible intracellular mechanisms to induce testicular deteriorations in rats at various concentrations and different time intervals. Sprague Dawley rats (n = 40) were allocated into four equal groups: the control one, and three other groups injected intra-peritoneally with AgNP solution 0.25, 0.5, and 1 mg/kg b.w. respectively for 15 and 30 days. Our findings revealed that AgNPs reduced body and testicular weights, estradiol (E2) and testosterone (T) hormone levels, and sperm parameters while elevating the nitric oxide and malondialdehyde levels with inhibition of reduced glutathione contents in testicular tissue. Interestingly, AgNPs significantly upregulated the testicular inducible nitric oxide synthase, B cell lymphoma 2 (Bcl-2)-associated X, transforming growth factor, and alpha-smooth muscle actin (α-SMA) expression levels. However, apurinic/apyrimidinic endo deoxyribonuclease 1 (APE1), NAD (P) H quinone dehydrogenase 1 (NQO1), and Bcl-2 expression levels were all downregulated indicating exhaustion of body antioxidant and repairing defense mechanisms in testicles in comparison with the control rats. Various histological alterations were also detected which dramatically increased in rats sacrificed after 30 days such as loss of the lining cells of seminiferous tubules with no spermatozoa and tubular irregularities associated with thickening of their basement membranes. Immunolabeling implicated in the apoptotic pathway revealed a negative expression of Bcl-2 and marked immunoreactivity for caspase-3 after 30 days of AgNP treatment in comparison to the control rats. To our knowledge, there have been no previous publications on the role of the α-SMA, APE1, and NQO1 genes in the molecular pathogenesis of AgNP testicular cytotoxicity following AgNP acute and chronic exposure.

Comparative evaluation of gold nanoparticles and Alum as immune enhancers against rabies vaccine and related immune reactivity, physiological, and histopathological alterations: in vivo study.

Purpose: The present study aimed to compare the immune-enhancing potential of gold nanoparticles (AuNPs) to Alum against rabies vaccine and the related immunological, physiological, and histopathological effects. Materials and Methods: Alum and AuNPs sole and in combination with rabies vaccine were used at 0.35 mg/mL and 40 nM/mL, respectively. Rats used were categorized into six groups (20/each): control rats, rabies vaccine, aluminum phosphate gel, rabies vaccine adsorbed to Alum, AuNPs, and rabies vaccine adjuvant AuNPs. Results: Liver and kidney functions were in the normal range after AuNPs and Alum adjuvanted vaccine compared to control. Interleukin-6 and interferon-γ levels were significantly increased in groups immunized with Alum and AuNPs adjuvanted vaccine, the peak level was in the case of AuNP adjuvanted vaccine on the 14th day. Ninety days post-vaccination, total immunoglobulin G (IgG) against adjuvanted rabies vaccine showed a significantly elevated anti-rabies IgG with AuNPs and Alum adsorbed vaccine compared with unadjuvanted one. The total antioxidant capacity, malondialdehyde (MDA) levels, superoxide dismutase, and glutathione peroxidase activities were significantly increased post-adjuvanted AuNPs adjuvanted vaccine vaccination than in Alum adsorbed vaccine, while MDA was significantly decreased. The histopathological examination revealed detectable alterations post-AuNPs and Alum adjuvanted vaccine immunization compared with liver and kidney profiles post-administration of unadjuvanted and non-immunized groups, meanwhile, splenic tissue revealed hyperplasia of lymphoid follicles indicating increased immune reactivity. Conclusion: The AuNPs are promising enhancers of the immune response as Alum, and the undesirable effects of AuNPs could be managed by using suitable sizes, shapes, and concentrations.