Understanding metabolic alterations after SARS-CoV-2 infection: insights from the patients' oral microenvironmental metabolites.

BACKGROUND: Coronavirus disease 2019 is a type of acute infectious pneumonia and frequently confused with influenza since the initial symptoms. When the virus colonized the patient's mouth, it will cause changes of the oral microenvironment. However, few studies on the alterations of metabolism of the oral microenvironment affected by SARS-CoV-2 infection have been reported. In this study, we explored metabolic alterations of oral microenvironment after SARS-CoV-2 infection. METHODS: Untargeted metabolomics (UPLC-MS) was used to investigate the metabolic changes between oral secretion samples of 25 COVID-19 and 30 control participants. To obtain the specific metabolic changes of COVID-19, we selected 25 influenza patients to exclude the metabolic changes caused by the stress response of the immune system to the virus. Multivariate analysis (PCA and PLS-DA plots) and univariate analysis (students' t-test) were used to compare the differences between COVID-19 patients and the controls. Online hiplot tool was used to perform heatmap analysis. Metabolic pathway analysis was conducted by using the MetaboAnalyst 5.0 web application. RESULTS: PLS-DA plots showed significant separation of COVID-19 patients and the controls. A total of 45 differential metabolites between COVID-19 and control group were identified. Among them, 35 metabolites were defined as SARS-CoV-2 specific differential metabolites. Especially, the levels of cis-5,8,11,14,17-eicosapentaenoic acid and hexanoic acid changed dramatically based on the FC values. Pathway enrichment found the most significant pathways were tyrosine-related metabolism. Further, we found 10 differential metabolites caused by the virus indicating the body's metabolism changes after viral stimulation. Moreover, adenine and adenosine were defined as influenza virus-specific differential metabolites. CONCLUSIONS: This study revealed that 35 metabolites and tyrosine-related metabolism pathways were significantly changed after SARS-CoV-2 infection. The metabolic alterations of oral microenvironment in COVID-19 provided new insights into its molecular mechanisms for research and prognostic treatment.

Embedding patient safety in a scaffold of interprofessional education; a qualitative study with thematic analysis.

BACKGROUND: Regardless of a proliferation of interest in reducing unsafe practices in healthcare, threats to patient safety (PS) remain high. Moreover, little attention has been paid towards the role of interprofessional education (IPE) in enhancing PS. This qualitative study was conducted to unfold the insights of the senior medical, dental and health sciences students at the University of Sharjah (UoS) in the United Arab Emirates (UAE) about PS in an online IPE-based workshop. METHODS: This inductive thematic analysis study was conducted on senior medical and health students at the Colleges of Medicine, Dental Medicine, Health Sciences, and Pharmacy of UoS. During an online workshop, students discussed plausible solutions for four real practice-based clinical scenarios with elements of unsafe healthcare practices. During the breakout rooms, the students exhibited high level of articulation and proactively participated in discussions. The data from the online workshop were transcribed and then coding, categorizing, and labelling of recurrent themes were carried out. Multiple individual deliberations, consolidation, incorporation of the identified preliminary themes, and merging and reorganizing sub-themes led to a final thematic framework. RESULTS: This work delved into the perspectives of 248 students regarding teamwork, communication, problem-solving, and other aspects concerning PS in interprofessional settings in an online workshop. The iterative process of data transcription, curating and qualitative analysis surfaced 32 codes. Later, the inductive themaric analysis yielded five themes with distinct yet interconnected nested subthemes in the context of PS in IPE settings. These themes of information sharing and grounding (problem-solving, social skills), maintaining communication (clinical reasoning, shared mental model), executing interprofessional activities (collaborative practice, collaboration scripts), professional cognitive abilities (cognitive maturity, metacognition), and negotiating professional identities (systematic change, socio-economic scaffolding) emerged as fundamental pillars for enhancing PS in healthcare. CONCLUSION: Our study demonstrated the outcome of an innovative and team-based workshop which embedded PS within a scaffold of IPE environment. This research calls for incorporation of the emerging areas of clinical reasoning, problem solving, collaborative practice, and shared mental model into medical curricula for structured IPE in improving PS domains in medical education. These findings underscore the need for multifaceted dimensions of IPE imperatives for cultivating collaborative competence.

Meloxicam loaded hydroxypropyl methylcellulose (HPMC) microparticulate: Fabrication, characterization and in vivo pharmacokinetic assessment.

Meloxicam (MEL) is an oxicam derivative with low water solubility that is useful in the treatment of colorectal cancer (CRC) as a COX-2 inhibitor. MEL-loaded HPMC micro particles were fabricated using an oil-in-oil (o/o) emulsion solvent evaporation (ESE) method. FTIR, XRD, particle size analysis, DSC, SEM and in vitro dissolution investigation were utilized to evaluate the produced micro particles physiochemically. Finally, rabbits were used as animal models in an in vivo pharmacokinetic study to assess the MEL concentration in the plasma of rabbits. Pure MEL, F1 and F2 were given to rabbits by a single dose for in vivo pharmacokinetic investigations. The XRD and DSC results confirmed the transformation of MEL from its crystalline nature to the amorphous state in micro particles. The formulations F1 and F2 particle sizes were determined 92.43µm and 163.26µm, respectively. The prepared micro particles had a smooth, non-porous and spherical surface. In comparison to the pure drug (22.4%), the F1 and F2 cumulative drug release (%) was 86.19% and 79.57%, respectively. Pure MEL, F1 and F2 have estimated Cmax values of 7.21, 25.41 and 22.38µg/mL, respectively. MEL had a half-life of 19.98 hours, which rose to 22.19 hours and 24.75 hours for F1 and F2, respectively. MEL, F1 and F2 had AUC0-α values of 116.034, 445.95 and 462.72µg/mL*h, respectively. Considering these aspects, MEL-loaded HPMC micro particles may have the potential to better the delivery and control the release of drug that is not easily dissolved in water which could lead to improved therapeutic efficacy and limited side effects.

Nanoniosome-encapsulated levoflaxicin as an antibacterial agent against Brucella.

A study was conducted to examine the prevalence of brucellosis (in animal farms) in the vicinity of Islamabad and Rawalpindi. A total of 170 milk samples were collected randomly from several farmhouses. The collected milk samples were initially screened by a Brucella selective medium. The bacterial isolates grown on the selective medium were subjected to biochemical identification for further confirmation of Brucella species. Among the tested samples, 28 (16.4%) were found positive for selective medium and 14 (8.2%) were found positive after biochemical confirmation. The antimicrobial susceptibility of several antibiotics performed by the disc-diffusion method did not yield any significant findings. Encapsulating antimicrobial drugs in unilamellar niosomes is an effective approach to treat the endemic infection. In this study, the antimicrobial activity of niosome-encapsulated levofloxacin is compared with free drug. The drug-encapsulating and empty niosomes were synthesized by using two surfactants Tween 80 and Span 40. Niosomal characterization included electron microscopy, dynamic light scattering, and zeta potential. The encapsulation efficiency was found to be 78% and 74% for Span 40 and Tween 80 niosomes, respectively. The antibacterial activity of niosomal levofloxacin was evaluated against the identified Brucella species and the antimicrobial activity of the free drug was increased many folds after encapsulation. In this study, levofloxacin niosomes were successfully synthesized against Brucellosis.

Electrophoretic Deposition of Copper(II)-Chitosan Complexes for Antibacterial Coatings.

Bacterial infection associated with medical implants is a major threat to healthcare. This work reports the fabrication of Copper(II)-Chitosan (Cu(II)-CS) complex coatings deposited by electrophoretic deposition (EPD) as potential antibacterial candidate to combat microorganisms to reduce implant related infections. The successful deposition of Cu(II)-CS complex coatings on stainless steel was confirmed by physicochemical characterizations. Morphological and elemental analyses by scanning electron microscopy (SEM) and energy-dispersive X-ray (EDX) spectroscopy verified the uniform distribution of copper in the Chitosan (CS) matrix. Moreover, homogeneous coatings without precipitation of metallic copper were confirmed by X-ray diffraction (XRD) spectroscopy and SEM micrographs. Controlled swelling behavior depicted the chelation of copper with polysaccharide chains that is key to the stability of Cu(II)-CS coatings. All investigated systems exhibited stable degradation rate in phosphate buffered saline (PBS)-lysozyme solution within seven days of incubation. The coatings presented higher mechanical properties with the increase in Cu(II) concentration. The crack-free coatings showed mildly hydrophobic behavior. Antibacterial assays were performed using both Gram-positive and Gram-negative bacteria. Outstanding antibacterial properties of the coatings were confirmed. After 24 h of incubation, cell studies of coatings confirms that up to a certain threshold concentration of Cu(II) were not cytotoxic to human osteoblast-like cells. Overall, our results show that uniform and homogeneous Cu(II)-CS coatings with good antibacterial and enhanced mechanical stability could be successfully deposited by EPD. Such antibiotic-free antibacterial coatings are potential candidates for biomedical implants.

Extraction, formulation and characterization of an in vitro and ex-vivo evaluation of Thymus serpyllum L. (Thymus oil) from topical preparations using dialysis cellulose membrane and natural rabbit skin.

Herbal remedies like the Thymus serpyllum L. is useful in traditional medicine for the treatment of many diseases especially congestion, and bronchitis. The purpose of this study was to formulate a micro-emulsion, a gel and an ointment containing the plant hydro distilled thymus oil extracted from Thymus serpyllum L. collected from Ziarat, Balochistan. The prepared formulations were subjected to in-vitro and ex vivo study release, High performance Liquid Chromatography (HPLC), Thin Layer Chromatography (TLC), to justify their suitability for topical use. The in-vitro and ex-Vivo release was studied using Franz Cells and using two different kinds of membrane synthetic dialysis cellulose membrane and natural rabbit skin and the amount of drug released was determined by HPLC at λ 274nm. The three formulations result obtained through dialysis cellulose membrane showed the faster release than the natural rabbit skin. However, the micro-emulsion, gel formulation showed the same release except ointment. The release from the above mentioned formulation can be arranged in the following descending order. micro-emulsion > Gel > Ointment. The best fit of release kinetics was achieved by Krosmeyer- Peppas, the TLC and HPLC identifies the Thymol, isolation and quantification of the marker. This study demonstrates that it is necessary to assess the impact of release and permeability pattern of different formulations. In vitro and ex-vivo diffusion cell experiments can be utilized to develop formulations of traditional medicines identifies.

Bioactive Constituents of Zanthoxylum rhetsa Bark and Its Cytotoxic Potential against B16-F10 Melanoma Cancer and Normal Human Dermal Fibroblast (HDF) Cell Lines.

Zanthoxylum rhetsa is an aromatic tree, known vernacularly as "Indian Prickly Ash". It has been predominantly used by Indian tribes for the treatment of many infirmities like diabetes, inflammation, rheumatism, toothache and diarrhea. In this study, we identified major volatile constituents present in different solvent fractions of Z. rhetsa bark using GC-MS analysis and isolated two tetrahydrofuran lignans (yangambin and kobusin), a berberine alkaloid (columbamine) and a triterpenoid (lupeol) from the bioactive chloroform fraction. The solvent fractions and purified compounds were tested for their cytotoxic potential against human dermal fibroblasts (HDF) and mouse melanoma (B16-F10) cells, using the MTT assay. All the solvent fractions and purified compounds were found to be non-cytotoxic to HDF cells. However, the chloroform fraction and kobusin exhibited cytotoxic effect against B16-F10 melanoma cells. The presence of bioactive lignans and alkaloids were suggested to be responsible for the cytotoxic property of Z. rhetsa bark against B16-F10 cells.

Permeation study through bacterial cellulose membrane.

Abstract: The objective of this study was to fabricate topical formulations of diclofenac diethylamine (DD) using isopropyl myristate (IPM) and isopropyl palmitate (IPP) as permeation enhancers. Franz cell and bacterial cellulose were used as analytical instrument and diffusion membrane, respectively. Permeation enhancers exhibited significant effect on the permeation characteristics of DD. It was concluded from the results that improved permeation of DD was observed when IPP was used as enhancer.

Clinico-radiographic study of odontogenic cysts at a tertiary care centre.

BACKGROUND: Cysts of the jaws constitute an important pathology in the oral and maxillofacial region and are broadly classified as odontogenic and non-odontogenic. Objective of this study was to document the clinical and radiographic presentation of odontogenic cysts at a tertiary care centre. METHODS: In this descriptive case-series, patients presenting with features of suspected cystic lesions of the jaws were investigated using radiographs and incisional biopsy. Subjects showing clinico- radiographic features of odontogenic cyst(s) with subsequent confirmation on histopathological examination were included. RESULTS: A total of 112 subjects were investigated for suspected jaw cysts and cystic diagnosis of odontogenic cysts was confirmed in 100 patients with 53 males (53%) and 47 females (47%). The age range of patients was from 12-55 years. Radicular cyst was the most commonly diagnosed odontogenic cyst (63%) followed by dentigerous cyst (22%) and odontogenickeratocyst (14%). Anterior maxilla was the most affected site (44%) followed by posterior mandible (30%). CONCLUSION: Odontogenic cysts constitute an established pathology affecting the jaws with varying frequency. This study augments the data cited from Western countries and re-emphasizes the need for early diagnosis and prompt management. It also highlights the differences in the presentation of odontogenic cysts as observed in the current series.

Excessive Dynamic Airway Collapse After Entecavir Use in a Patient With Pegylated Interferon-Induced Undifferentiated Connective Tissue Disease and Entecavir Use to Prevent Hepatitis B Virus Reactivation Upon Giving Rituximab.

Pegylated interferon-alpha (PEG-IFN-α) is an antiviral medication used to treat chronic hepatitis C virus (HCV) and hepatitis B virus (HBV) infections. It may result in rare but severe side effects, such as undifferentiated connective tissue disease (UCTD) and excessive dynamic airway collapse (EDAC), which can occur as delayed complications of PEG-IFN-α-induced UCTD. In cases where these complications arise, entecavir, employed for treating HBV infection, may be considered. A 49-year-old female patient, monitored for nine years with HCV and a viral load of 1.5 million, genotype 3, and normal liver function tests (LFTs), possibly acquired the infection from her HCV-positive husband. The patient was initially treated with PEG-IFN-α (IFN-α-2b, 100 µg/week subcutaneously) and ribavirin (RBV, 500 mg/twice daily). Following the sixth injection, the patient exhibited symptoms, including shortness of breath and cough, leading to limited daily activities. Subsequent high-resolution computed tomography (HRCT) showed interstitial pneumonitis (IP) signs. She was given a high dose of steroids. Over the next two to four weeks, the patient experienced Raynaud's phenomenon, skin tightening, joint pains, and dryness of the eyes and mouth. The antinuclear antibody (ANA) test was negative, while the extractable nuclear antigen (ENA) test showed equivocal anti-Smith antibodies (6.38). Rheumatoid factor (RA) factors were mildly positive, and pulmonary function tests (PFTs) indicated a restrictive pattern. The patient was intolerant to hydroxychloroquine (HCQ) and azathioprine (Imuran) 500 mg, subsequently receiving mycophenolate mofetil 500 mg/thrice daily. Despite four years of treatment, UCTD due to PEG-IFN-α remained difficult to control; however, IP responded well to steroids. Rituximab pulse therapy was planned before the initiation; serological tests showed positive anti-HBs with a titer of 17.02, positive anti-HBc, but negative HBsAg and undetectable HBV viral load, indicating immunity to HBV due to natural infection. Given the potential for rituximab to cause immunosuppression and HBV reactivation, entecavir treatment was started and continued for 18 months. The patient was followed for another five years, during which her LFTs and viral markers showed stability. However, after nine years of PEG-IFN-α-induced UCTD disorder, she experienced a reoccurring cough but was unresponsive to steroids that were against her suspicion of a flare of IP. A subsequent dynamic CT scan detected a 75% trachea collapse while in a supine position, indicating a potential complication termed EDAC. This EDAC could not be linked to PEG-IFN-α-induced UCTD disorder or EDAC after the use of entecavir in a patient with PEG-IFN-α-induced UCTD disorder. Treatment of such complex patients requires flexible, specific treatment plans and continuous monitoring. This case emphasizes the need for caution in patients with a history of IFN-induced disease and the possibility of late effects and possible effects of the use of entecavir in a patient with PEG-IFN-α-induced UCTD. To the best of our knowledge, this is the first case reported as EDAC, a possible delayed complication of PEG-IFN-α plus ribavirin or entecavir in a patient with PEG-IFN-α-induced UCTD.

Reproductive and metabolic toxic effects of polystyrene microplastics in adult female Wistar rats: a mechanistic study.

Microplastics, such as polystyrene microplastics (PS-MPs), have become an emerging environmental hazard for animals and humans. Long-term exposure to PS-MPs has led to neurotoxicity, reproductive dysfunction, and carcinogenesis. The goal of this study was to evaluate the effect of sub-chronic exposure of PS-MPs on metabolic and reproductive functions in female rats. The PS-MPs were prepared by cryogenic technique. The PS-MPs were given orally to female Wistar rats for 45 days at 2.5, 5, and 10 mg/kg/day. The average PS-MPs' size diameter was 876 nm. The PS-MPs administration resulted in a significant decrease in the activity of superoxide dismutase and catalase in the liver and ovary. The effect of PS-MPs on reduced glutathione and lipid peroxidation in the liver and ovarian tissues of rats was statistically insignificant. The PS-MP exposure exhibited an increase in the levels of triglycerides, total cholesterol, and low-density lipoprotein and decrease in high-density lipoprotein. The PS-MPs caused glucose intolerance and increase in insulin. Moreover, the PS-MP exposure increased follicle stimulating hormone, estradiol, and testosterone. Serum level of interleukin-6 and nuclear factor kappa B (NF-κB) was elevated in animals treated with PS-MPs. The PS-MP exposed rats showed normal ovarian histology, but activated hepatic stellate cells and liver fibrosis. It is concluded that the sub-chronic exposure to PS-MPs resulted in metabolic and endocrine disruption in female rats through oxidative damage, hormonal imbalance, and chronic inflammation.

Adverse health effects and mechanisms of microplastics on female reproductive system: a descriptive review.

Microplastics (MPs), with a diameter of less than 5 mm, include polymers such as polystyrene, polypropylene, and polyethylene. The MPs occur in different morphologies including fragments, beads, fibers, and films that are swallowed by fresh water and land-based animals and enter their food chain, where they produce hazardous effects such as uterine toxicity, infertility, and neurotoxicity. The aim of this review is to explore the effects of polystyrene MPs (PS-MPs) on the female reproductive system and understand the mechanisms by which they produce reproductive toxicity. Several studies suggested that the exposure to PS-MPs increased the probability of larger ovaries with fewer follicles, decreased the number of embryos produced, and decreased the number of pregnancies in female mice. It also changed sex hormone levels and caused oxidative stress, which could have an impact on fertility and reproduction. Exposure to PS-MPs caused the death of granulosa cells through apoptosis and pyroptosis via activation of the NLRP3/caspase pathway and disruption of the Wnt-signaling pathway. Activation of TL4/NOX2 caused the uterine fibrosis resulting in endometrium thinning. The PS-MPs had a negative impact on ovarian capacity, oocyte maturation, and oocyte quality. Furthermore, the PS-MPs disrupted the hypothalamus-pituitary-gonadal axis in marine animals, resulting in a decrease in hatching rate and offspring body size, causing trans-generational effects. It also reduced fecundity and produced germ-line apoptosis. The main focus of this review was to explore the different mechanisms and pathways through which PS-MPs adversely impact the female reproductive system.

Wood as a green and sustainable alternative for environmentally friendly & flexible electronic devices.

Electronic are usually constructed from non-renewable, non-biodegradable, and hazardous materials. Due to the frequent upgrading or discarding of electronic devices, which contributes significantly to environmental pollution, there is a high demand for electronics made from renewable and biodegradable materials with less harmful components. To this end, due to their flexibility, strong mechanical, and optical properties, wood-based electronics have become very appealing as substrates especially for flexible electronics and optoelectronics. However, incorporating numerous features including high conductivity and transparency, flexibility, and mechanical robustness into an environmentally friendly electronic device remains very challenging. Herein, authors have provided the techniques used to fabricate sustainable wood based flexible electronics coupled with their chemical, mechanical, optical, thermal, thermomechanical, and surface properties for various applications. Additionally, the synthesis of a conductive ink based on lignin and the development of translucent wood as a substrate are covered. Future developments and broader applications of wood-based flexible materials are discussed in the final section of the study, with an emphasis on their potential in fields including wearable electronics, renewable energy, and biomedical devices. This research improves upon prior efforts by demonstrating new ways to simultaneously attain better mechanical and optical qualities and environmental sustainability.

Synthesis, characterization and adsorption behavior of modified cellulose nanocrystals towards different cationic dyes.

Green and efficient removal of polluted materials are essential for the sustainability of a clean and green environment. Nanomaterials, particularly cellulose nanocrystals (CNCs), are abundant in nature and can be extracted from various sources, including cotton, rice, wheat, and plants. CNCs are renewable biomass materials with a high concentration of polar functional groups. This study used succinic anhydride to modify the surface of native cellulose nanocrystals (NCNCs). Succinic anhydride has been frequently used in adhesives and sealant chemicals for a long time, and here, it is evaluated for dye removal performance. The morphology and modification of CNCs studied using FTIR, TGA & DTG, XRD, SEM, AFM, and TEM. The ability of modified cellulose nanocrystals (MCNCs) to adsorb cationic golden yellow dye and methylene blue dye was investigated. The MCNCs exhibited high adsorption affinity for the two different cationic dyes. The maximum adsorption efficiency of NCNCs and MCNCs towards the cationic dye was 0.009 and 0.156 wt%. The investigation for adhesive properties is based on the strength and toughness of MCNCs. MCNCs demonstrated improved tensile strength (2350 MPa) and modulus (13.9 MPa) using E-51 epoxy system and a curing agent compared to 3 wt% composites. This research lays the groundwork for environmentally friendly fabrication and consumption in the industrial sector.

The severity of COVID-19 in hypertensive patients is associated with mirSNPs in the 3' UTR of ACE2 that associate with miR-3658: In silico and in vitro studies.

The SARS-CoV-2 virus targets the antigen converting enzyme 2 (ACE2) receptor, thus resulting in elevated morbidity and an increased risk of severe and fatal COVID-19 infection in individuals with hypertension and diabetes mellitus. Objectives: This study aimed to identify the association between increased susceptibility and severity in order to evaluate their impact in hypertensive COVID-19 patients using in vitro and in silico models. Methods: We identified 80 miRNA binding sites on ACE2 (for different miRNAs) as well as various 30 SNPs in the miRNA binding sites of the 3' untranslated region (3' UTR) in the ACE2 gene using different online software and tools. From August 2020 to August 2021, a total of 200 nasopharyngeal/mouth swabs samples were collected from Multan, Pakistan. In order to quantify the cDNA of ACE2 and miR-3658 genes, we used Rotor Gene qRT-PCR on hypertensive patients with COVID-19 as well as healthy controls. Results: Interestingly, the binding site of miR-3658 corresponding to the 3' UTR of ACE2 featured three SNPs (rs1457913029, C>T; rs960535757, A>C, G; rs1423809569, C>T), and its genomic sequence featured a single SNP (rs1024225815, C>T) with the same nucleotide variation (rs1457913029, C>T) which potentially increases the severity of COVID-19. Similarly, three other SNPs (rs1557852115, C>G; rs770335293, A>G; rs1024225815, C>T) were also found on the first binding site positions of miR-3658. Our in vitro study found that ACE2 gene expression had an effect on miR-3658 in COVID-19 patients who also had hypertension. In both cases, our analysis demonstrated that the in silico model captured the same biological mechanisms as the in vitro system. Conclusion: The identified SNPs could represent potential informative signatures owing to their position in the splicing site of the ACE2 gene.

Glutathione treatment suppresses the adverse effects of microplastics in rice.

Oryza sativa is grown worldwide and exhibit sensitivity to different stresses. Exponential increase in microplastics in agroecosystems is damaging and demand pragmatic strategies to protect growth and yield losses. We evaluated exogenous application of different doses of glutathione (GSH) for mediation of physiological traits of rice plants experiencing two different MPs i.e. PET and HDPE in root zone. All the rice seedlings exhibited MP-induced significant (P ≤ 0.001) growth inhibition compared to the control plants. GSH application (T3) significantly increased the shoot fresh weight (8.80%), root fresh weight (19.22%), shoot dry weight (13.705%), root dry weight (25.52%), plant height (5.75%) and 100-grain weight (9.36%), compared to control plants. GSH treated plants (T4) showed a recovery mechanism by managing the marginal rate of reduction of all photosynthetic and gas exchange attributes by showing 34.44, 20.98, 34.83, 42.16, 39.70, and 51.38% reduction for Chl-a, Chl-b, total cholophyll, photosynthetic rate (A), transpiration rate (E), and stomatal conductance (Gs), respectively, compared to control plants. Under 5 mg L-1 HDPE and PET, rice seedlings without GSH treatment responded in terms of increase in total soluble sugar, total free amino acid, glutathione, glutathione disulfide contents, while total soluble protein and ascorbic acid contents decreased significantly, compared with control plants. Corrleation matrix revealed positive relationship between GSH and improvement in studied attributes. Moreover, exogenous GSH improved rice growth and productivity to counter the negative role of MPs. This unique study examined the effects of GSH on rice plants growing in MP-contaminated media and revealed how exogenous GSH helps plants survive MP-stress.

Surgical Management Of Irreducible Atlanto-Axial Dislocation With OS Odontoideum And Klippel-Feil Syndrome.

Klippel-Feil syndrome (KFS) is the congenital fusion of two or more cervical vertebrae which is often associated with various other abnormalities in the cervical spine. Involvement the upper cervical segments leads to atlanto-axial instability which manifests as progressive neurological symptoms due to compression on the spinal cord. These cases pose a surgical challenge due the abnormal and unique anatomy of each patient. A 37-year-old patient presented with neck pain and cervical myelopathy due to a posterior subluxation of C2-3 fused segment over C4-6 fused segment. The patient had an os odontoideum, incomplete posterior arch of C1, anomalous course of vertebral artery and C3 hemi-vertebra. The patient was successfully managed with transoral odontoidectomy and occipeto-cervical fusion. Irreducible atlanto-axial dislocation in a patient with an abnormal upper cervical spine anatomy may require transoral decompression followed by posterior fusion.

Anterior transcervical release with posterior atlantoaxial fixation for neglected malunited type II odontoid fractures.

Background: Type 2 odontoid fractures are associated with a high rate of nonunion without surgical treatment. If neglected, they may become fixed in an abnormal position, causing progressive myelopathy. Conventionally, odontoidectomy or transoral release is performed to relieve symptoms in such cases. Here, were report our experience with a transcervical approach for odontoid release (i.e., of a chronically fractured dens) followed by a posterior C1-C2 fusion. Methods: The 11 patients (2017-2021) retrospectively included; in this study, all had a history of remote trauma and the radiological appearance of an old odontoid fracture that was displaced and could not be reduced with traction. There were eight males and three females who averaged 52.6 years of age. Results: All 11 patients underwent anterior retropharyngeal release with a C4-C5 level incision followed by a posterior C1-C2 fusion. The mean Japanese orthopedic association on presentation was 9.9 ± 2.7 which improved to 13.8 ± 2.7 on final follow-up (P < 0.01). Patients were followed an average of 9.6 months ± 4.4 (mean ± SD) postoperatively during which time they all clinically improved. Conclusion: Anterior release through a retropharyngeal approach coupled with posterior C1-C2 instrumentation proved to be an effective alternative to the traditional transoral approach to treat a chronic malunited odontoid fracture.

Mitochondrial Dysfunction and Antioxidation Dyshomeostasis-Enhanced Tumor Starvation Synergistic Chemotherapy Achieved using a Metal-Organic Framework-Based Nano-Enzyme Reactor.

Exploiting zeolitic imidazolate framework (ZIF)-based nanoparticles to synergistically enhance starvation-combined chemotherapy strategies remains an urgent demand. Herein, glucose oxidase (GOX) and doxorubicin (DOX) were facilely incorporated into ZIFs for starvation-combined chemotherapy. The as-prepared DOX/GOX-loaded ZIF (DGZ) exhibited uniform size with good dispersity, effective protection of the GOX activity, and stable delivery of the drugs into tumor. Correspondingly, it could achieve the glucose- and pH-responsive degradation and thus the controllable drug release. As a result, the acidification of glucose accompanied with reactive oxygen species (ROS) production was observed for the starvation-enhanced chemotherapy and the improved degradation. Most importantly, adjustable Zn2+ release was achieved with the biodegradation of DGZ, which thus contributed to an augmented therapeutic outcome via the Zn2+-induced mitochondrial dysfunction and antioxidation dyshomeostasis. These findings, synergized with the enhancement of starvation-combined chemotherapy by inhibiting the mitochondrial energy metabolism and boosting the ROS accumulation using pristine ZIF-based nanoparticles, provide a new insight into the metal-organic framework-based nanomedicine for further cancer treatments.

The design of cell-selective tryptophan and arginine-rich antimicrobial peptides by introducing hydrophilic uncharged residues.

Antimicrobial peptides (AMPs) are considered to be powerful weapons in the fight against traditional antibiotic resistance due to their unique membrane-disruptive mechanism. The combination of traditional and classical hydrophobic tryptophan (W) residues and hydrophilic charged arginine (R) residues is considered as the first choice for the minimalist design of AMPs due to its potent performance in antibacterial activity. However, some W- and R-rich AMPs that are not rationally designed and contain excessive repeats of W and R residues may cause severe cytotoxicity and hemolysis. To address this issue, we designed the (WRX)n (where X = hydrophilic uncharged amino residues; n = number of repeat units) series engineered peptides with high cell selectivity by introducing hydrophilic uncharged threonine (T), serine (S), glutamine (Q) or asparagine (N) residues into the minimalist design of W- and R-rich AMPs. The results showed that the introduction of these hydrophilic uncharged amino residues, especially T residues, significantly improved the cell selectivity of the W- and R-rich engineered peptides. Among (WRX)n series engineered peptides, T6 presents a mixture structure of ß-turn and α-helix. It has broad spectrum and potent antibacterial activity (no activity against probiotics), good biocompatibility, high selectivity index, strong tolerance (physiological salts, serum acid, alkali, and heat conditions), rapid and efficient time-kill kinetics, and no tendency of resistance. Studies on antibacterial mechanism show that T6 exert antibacterial activity mainly by disrupting bacterial cell membrane and inducing the accumulation of reactive oxygen species in bacterial cells. Furthermore, T6 exhibited potent antibacterial and antiinflammatory capabilities in vivo in a mouse peritonitis-sepsis model infected with Escherichia coli. In conclusion, our study confirms an effective strategy for the minimalist design of highly cell selective W- and R-rich AMPs by introducing hydrophilic uncharged T residues, which may trigger widespread attention to hydrophilic uncharged amino acid residues, including T residues, and provide new insights into the design of peptide-based antibacterial biomaterials. STATEMENT OF SIGNIFICANCE: We have introduced hydrophilic uncharged T, S, Q or N residues into the minimalist design of W- and R-rich engineered peptides and found that the introduction of these hydrophilic uncharged amino residues, especially the T residues, can significantly improve the cell selectivity of W- and R-rich engineered peptides. The target compound T6 showed potent antibacterial activity, high cell selectivity, strong tolerance, good in vivo efficacy and killed bacteria through multiple mechanisms mainly membrane-disruptive. These findings may spark widespread interest in hydrophilic uncharged amino acid residues, and provide new insights into the design of peptide-based antimicrobial biomaterials.