The Promise and Potential of Metal-Organic Frameworks and Covalent Organic Frameworks in Vaccine Nanotechnology.

The immune system's complexity and ongoing evolutionary struggle against deleterious pathogens underscore the value of vaccination technologies, which have been bolstering human immunity for over two centuries. Despite noteworthy advancements over these 200 years, three areas remain recalcitrant to improvement owing to the environmental instability of the biomolecules used in vaccines─the challenges of formulating them into controlled release systems, their need for constant refrigeration to avoid loss of efficacy, and the requirement that they be delivered via needle owing to gastrointestinal incompatibility. Nanotechnology, particularly metal-organic frameworks (MOFs) and covalent organic frameworks (COFs), has emerged as a promising avenue for confronting these challenges, presenting a new frontier in vaccine development. Although these materials have been widely explored in the context of drug delivery, imaging, and cancer immunotherapy, their role in immunology and vaccine-related applications is a recent yet rapidly developing field. This review seeks to elucidate the prospective use of MOFs and COFs for biomaterial stabilization, eliminating the necessity for cold chains, enhancing antigen potency as adjuvants, and potentializing needle-free delivery of vaccines. It provides an expansive and critical viewpoint on this rapidly evolving field of research and emphasizes the vital contribution of chemists in driving further advancements.

Biolistic delivery of liposomes protected in metal-organic frameworks.

Needle-and-syringe-based delivery has been the commercial standard for vaccine administration to date. With worsening medical personnel availability, increasing biohazard waste production, and the possibility of cross-contamination, we explore the possibility of biolistic delivery as an alternate skin-based delivery route. Delicate formulations like liposomes are inherently unsuitable for this delivery model as they are fragile biomaterials incapable of withstanding shear stress and are exceedingly difficult to formulate as a lyophilized powder for room temperature storage. Here we have developed a approach to deliver liposomes into the skin biolistically-by encapsulating them in a nano-sized shell made of Zeolitic Imidazolate Framework-8 (ZIF-8). When encapsulated within a crystalline and rigid coating, the liposomes are not only protected from thermal stress, but also shear stress. This protection from stressors is crucial, especially for formulations with cargo encapsulated inside the lumen of the liposomes. Moreover, the coating provides the liposomes with a solid exterior that allows the particles to penetrate the skin effectively. In this work, we explored the mechanical protection ZIF-8 provides to liposomes as a preliminary investigation for using biolistic delivery as an alternative to syringe-and-needle-based delivery of vaccines. We demonstrated that liposomes with a variety of surface charges could be coated with ZIF-8 using the right conditions, and this coating can be just as easily removed-without causing any damage to the protected material. The protective coating prevented the liposomes from leaking cargo and helped in their effective penetration when delivered into the agarose tissue model and porcine skin tissue.

Apoptosis in Alzheimer's disease: insight into the signaling pathways and therapeutic avenues.

Alzheimer's disease (AD) is characterized by the accumulation of hyperphosphorylated tau and amyloid-ß (Aß) protein resulting in synaptic loss and apoptosis. Aß and tau deposition trigger apoptotic pathways that result in neuronal death. Apoptosis is considered to be responsible for manifestations associated with AD under pathological conditions. It regulates via extrinsic and intrinsic pathways. It activates various proteins including Bcl-2 family proteins like Bax, Bad, Bid, Bcl-XS, Bcl-XL and caspases comprising of initiator, effector and inflammatory caspases carried out through a cascade of events that finally lead to cell disintegration. The apoptotic elements interact with trophic factors, signaling molecules including Ras-ERK, JNK, GSK-3ß, BDNF/TrkB/CREB and PI3K/AKT/mTOR. Ras-ERK signaling is involved in the progression of cell cycle and apoptosis. JNK pathway is also upregulated in AD which results in decreased expression of anti-apoptotic proteins. JAK-STAT triggers caspase-3 mediated apoptosis leading to neurodegeneration. The imbalance between autophagy and apoptosis is regulated by PI3K/Akt/mTOR pathway. GSK-3ß is involved in the stimulation of pro-apoptotic factors resulting in dysregulation of apoptosis. Drugs like filgrastim, epigallocatechin gallate, curcumin, nicergoline and minocycline are under development which target these pathways and modulate the disease condition. This study sheds light on apoptotic pathways that are cardinal for neuronal survival and perform crucial role in the occurrence of AD along with the trends in therapeutics targeting apoptosis induced AD. To develop prospective treatments for AD, it is desirable to elucidate potential targets including restoration apoptotic balance, regulation of caspases, Bcl-2 and other crucial proteins involved in apoptosis mediated AD.

Geochemical characteristics of the Rajmahal coals in Dhulia North Block, Eastern India: implication to their utilization and environment.

The borehole coal samples of Dhulia North Block from the Rajmahal Basin, Eastern India, were systematically analyzed based on the chemical composition and concentration of major and trace elements (including rare earth elements, REEs) to assess the distribution of REEs and their environmental implications with utilization potential. The Dhulia North Block coals are characterized by the predominant major oxides of SiO2, Al2O3, and Fe2O3, accounting for 94% of the total ash composition, indicating the presence of quartz, clay-rich minerals, and pyrite. Compared with the average world coal ash, the total REE content in the analyzed samples ranged from 341.0 to 810.4 ppm, which is substantially higher. Hot humid climate conditions with intermediate igneous source rocks of the basin were demonstrated by the major oxide ratios (Al2O3/TiO2 < 20) and plots of TiO2 with Al2O3 and Zr. The redox-sensitive elements such as V, Ni, Cr, and Co found in the Dhulia North Block coal indicate that an oxic sedimentary environment existed in the basin when coal was formed. The low sulfur content (1% in most samples) indicates freshwater conditions in the basin at the time of organic matter deposition. The outlook coefficient (Coutl) varies between 0.7 and 1.6, indicating that the Dhulia North Block coals are a prospective source of REEs. The Dhulia North Block coals are characterized by low H/C and O/C atomic ratios ranging from 0.56 to 0.90 and 0.10 to 0.22, respectively, and contain type-III kerogens, indicating gas-prone source rock. Further, the basic-to-acid oxide ratio suggested that Dhulia North Block coals were suitable for utilization during combustion processes.

Protective effects of intranasal curcumin on silica-induced lung damage.

OBJECTIVE: Being anti-inflammatory and an antioxidant in nature, curcumin has been studied for its anti-asthmatic effects, but its impact on silicosis has not been investigated before. It is a form of occupational lung illness caused by inhaling crystalline silica. It is particularly common among those who work in construction-related sectors. Therefore, present study has been undertaken to investigate impact of intranasal curcumin on silica induced lung damage in mice model of silicosis. MATERIALS AND METHODS: Mice model of silicosis was developed by intranasal silica instillation (2.5 mg/mice) for different durations mainly 7, 14 and 21 days, where the longest duration of silica exposure (21 days) mimics chronic occupational exposure of silica dust leading to silicosis. Curcumin (5 mg/kg,i.n) and /or dexamethasone, a known corticosteroid (10 mg/kg,i.p) was administered an hour prior to silica administration. RESULTS: Present study revealed silica induced lung damage in the mice model of silicosis characterized by airway inflammation, collagen deposition and enhanced expression of fibrosis markers (MMP-9, α-SMA, Hydroxyproline), which were significantly reduced in curcumin treatment groups. Inhibitory effects of curcumin were compared with standard drug, dexamethasone, a corticosteroid and was found better in protecting structural alterations in the lung. Damaged and abnormal mitochondria (enlarged and irregular shapes) were observed in silicosis group which were reduced in curcumin and dexamethasone treatment groups as revealed in transmission electron microscopic studies. CONCLUSIONS: Present study shows protective effects of intranasal curcumin on silica-induced airway inflammation and structural changes thereby lung damage. Hence, it can be considered as an alternative and complementary medication for silicosis.

Repeated Silica exposures lead to Silicosis severity via PINK1/PARKIN mediated mitochondrial dysfunction in mice model.

BACKGROUND AND OBJECTIVES: Silicosis, one of the occupational health illnesses is caused by inhalation of crystalline silica. Deposition of extracellular matrix and fibroblast proliferation in lungs are linked to silicosis development. Mitochondrial dysfunction plays critical role in some diseases, but how these processes progress and regulated in silicosis, remains limited. Detailed study of silica induced pulmonary fibrosis in mouse model, its progression and severity may be helpful in designing future therapeutic strategies. METHODS: In present study, mice model of silicosis has been developed after repeated silica exposures which may closely resemble clinical symptoms of silicosis in human. In addition to efficiently mimicking the acute/chronic transformation processes of silicosis, this is practical and efficient in terms of time and output, which avoids mechanical injury to the upper respiratory tract due to surgical interventions. Sonicated sterile silica suspension (120 mg/kg) was administered through intranasal route thrice a week at regular intervals (21, 28 and 35 days). RESULTS: Presence of minute to larger silicotic nodules in H&E-stained lung sections were observed in all silica induced model groups. Enhanced ECM deposition was noted in MT stained lung sections of silica exposure groups as compared to control which were confirmed by significantly higher MMP9 expression levels and hydroxyproline content in silica 35 days group. Increase in Reactive oxygen species (ROS), inflammatory cell recruitment mainly, neutrophils and macrophage were observed in all three silica exposure groups. Transmission electron microscopic analysis has confirmed presence of many aberrant shaped mitochondria (swollen, round shape) in 35 days model where autophagosomes were minimum. Western blot analysis of mitophagy and autophagy markers such as Pink1, Parkin, Cytochrome c, SQSTM1/p62, the ratio of light chain LC3B II/LC3B I was found higher in 21 and 28 days which were significantly reduced in 35 days silica model. CONCLUSIONS: Higher MMP9 activity and MMP9 /TIMP1 ratio demonstrate excessive extracellular matrix damage and deposition in 35 days model. Significantly reduced expressions of autophagy and mitophagy markers have also confirmed progression in fibrosis severity and its association with repeated silica exposures in 35 days model group.

Investigating temperature variability on antioxidative behavior of synthesized cerium oxide nanoparticle for potential biomedical application.

Cerium oxide nanoparticles (CNP) have garnered significant attention due to their versatile redox properties and wound-healing applications. The antioxidative nature of CNP is due to its ability to be oxidized and reduced, followed by the capture or release of oxygen which is used for scavenging reactive oxygen species (ROS). Herein, CNP is produced through a wet chemistry approach and its tunable redox property is tested across a range of temperatures. The synthesized CNP was observed to reveal the signature peak at 245 nm indicating a high Ce+3/Ce+4 ratio. Towards evaluating the redox antioxidative behavior, CNPs were subjected to a comprehensive analysis for superoxide dismutase mimetic analysis with riboflavin-mediated nitroblue tetrazolium scavenging assay. The results demonstrated that the redox activity of cerium oxide nanoparticles was strongly influenced by the different temperature ranges. Superoxide dismutase mimetic activity was observed to be reduced with a decrease in temperature as we moved from 4°C (80% activity) to -80°C (47% activity) at 1 mM conc of CNP. Similarly, the SOD mimetic activity increased with an increase in temperature from 40°C (72% activity) to 70°C (94% activity). Further, CNP was found to inhibit E. coli (gram+ve) and Enterobacter (gram-ve) beyond 70% simultaneously at 1 mM conc, indicating its potential application as a remarkable antimicrobial agent. CNP also inhibited the alpha-amylase activity up to the 60% at 1 mM conc suggesting its potential application in antidiabetic wound healing therapy. Overall, the CNP finds its application in mitigating the oxidative stress-related disorder exhibited by its high antioxidative, antimicrobial, and antidiabetic behavior.

Ocimum sanctum: The Journey from Sacred Herb to Functional Food.

In recent years, the growing demand for herbal-based formulations, including functional foods, has acquired significant attention. This study highlights historical, botanical, ecological, and phytochemical descriptions and different extraction mechanisms of Ocimum sanctum utilized in its processing. Besides this, it explores the utilization of Ocimum sanctum as a functional food ingredient in various food products such as bakery products (biscuits, bread), dairy products (herbal milk, cheese), and beverages (tea, juice, wine) while focusing on their evaluation parameters, preparation techniques, and pharmacological activities. In terms of other pharmacological properties, Ocimum sanctum-infused functional foods exhibited cognitiveenhancing properties, adaptogenic qualities, anti-obesity effects, gastroprotective, antiinflammatory, hypoglycemic, and immuno-modulatory effects. Thus, the diverse properties of Ocimum sanctum offer exciting opportunities for the development of functional foods that can promote specific health issues, so future research should focus on developing and analyzing novel Ocimum sanctum-based functional foods to meet the growing demand of the functional food industry.

Update on monkeypox virus infection: Focusing current treatment and prevention approaches.

BACKGROUND: While the world is still facing the global pandemic COVID-19, another zoonosis monkeypox (Mpox) has emerged posing a great threat to society. Insight into the pathogenesis, symptoms, and management strategies will aid in the development of potent therapeutics for the treatment of monkeypox virus infection. OBJECTIVES: To get insight into the current treatment and prevention strategies will aid in effectively coping with the disease. METHODS: For obtaining information regarding the ongoing treatment and prevention strategies and the drugs under pipeline, we referred to Google Scholar, Pub Med, Pub Chem, and WHO official site. RESULTS: There are a few drugs that came out to be effective for the treatment of Mpox. Tecovirimat acts by inhibiting viral replication and viral wrapping. Another drug is cidofovir, which hinders the activity of viral DNA polymerase but has the drawback of nephrotoxicity. To overcome this, a conjugate of cidofovir is being used-known as brincidofovir-which has a similar mechanism as cidofovir but lesser toxicity. Ribavirin acts via inhibiting inosine monophosphate dehydrogenase (IMPDPH) thus disrupting viral translation. It also interferes with helicase activity. Tiazofurin, Adenosine N1 oxide, and HPMPA have shown efficacy in in-vitro studies by inhibiting IMPDH, DNA polymerase, and viral mRNA translation respectively. In-silico studies have proven the effect of nilotinib, simeprevir, and dihydroergotamine for Mpox treatment. They have shown binding affinity for proteins required for the growth and release of MPXV. Vaccines have also been employed for the prevention of Mpox, which includes JYNNEOS, ACAM2000, and VIGIV. CONCLUSION: This review highlights the pathogenesis of the virus, disease manifestations, drugs, and vaccines that are being used and those under pipeline for the treatment and prevention of Mpox.

A scalable synthesis of adjuvanting antigen depots based on metal-organic frameworks.

Vaccines have saved countless lives by preventing and even irradicating infectious diseases. Commonly used subunit vaccines comprising one or multiple recombinant proteins isolated from a pathogen demonstrate a better safety profile than live or attenuated vaccines. However, the immunogenicity of these vaccines is weak, and therefore, subunit vaccines require a series of doses to achieve sufficient immunity against the pathogen. Here, we show that the biomimetic mineralization of the inert model antigen, ovalbumin (OVA), in zeolitic imidazolate framework-8 (ZIF-8) significantly improves the humoral immune response over three bolus doses of OVA (OVA 3×). Encapsulation of OVA in ZIF-8 (OVA@ZIF) demonstrated higher serum antibody titers against OVA than OVA 3×. OVA@ZIF vaccinated mice displayed higher populations of germinal center (GC) B cells and IgG1+ GC B cells as opposed to OVA 3×, indicative of class-switching recombination. We show that the mechanism of this phenomenon is at least partly owed to the metalloimmunological effects of the zinc metal as well as the sustained release of OVA from the ZIF-8 composite. The system acts as an antigen reservoir for antigen-presenting cells to traffic into the draining lymph node, enhancing the humoral response. Lastly, our model system OVA@ZIF is produced quickly at the gram scale in a laboratory setting, sufficient for up to 20 000 vaccine doses.

Insight into the emerging and common experimental in-vivo models of Alzheimer's disease.

Alzheimer's disease (AD) is a multifactorial, rapidly progressing neurodegenerative disorder. As the exact cause of the disease is still unclear, the drug development is very challenging. This review encompasses the commonly used AD models involving various chemicals, heavy metals and endogenous substances induced models and the transgenic models. It also provides insight into the reliable emerging models of AD that may overcome the shortcomings associated with available models. Chemicals like streptozotocin, scopolamine, colchicine and okadaic acid render the animal susceptible to neuroinflammation and oxidative stress induced neurodegeneration along with amyloid-ß deposition and tau hyperphosphorylation. Similarly, endogenous substances like acrolein and amyloid-ß 1-42 are efficient in inducing the major pathologies of AD. Heavy metals like aluminum and fluoride and mixture of these have been reported to induce neurotoxicity therefore are used as animal models for AD. Transgenic models developed as a result of knock-in or knock-out of certain genes associated with AD including PDAPP, APP23, Tg2576, APP/PS1, 3 × Tg and 5 × FAD have also been incorporated in this study. Further, emerging and advanced pathomimetic models of AD are provided particular interest here which will add on to the current knowledge of animal models and may aid in the drug development process and deepen our understanding related to AD pathogenesis. These newly discovered models include oAß25-35 model, transgenic model expressing 82-kDa ChAT, oDGal mouse and APP knock-in rat. This study may aid in the selection of suitable model for development of novel potent therapeutics and for exploring detailed pathogenic mechanism of AD.

Predicting near-term glaucoma progression: An artificial intelligence approach using clinical free-text notes and data from electronic health records.

Purpose: The purpose of this study was to develop a model to predict whether or not glaucoma will progress to the point of requiring surgery within the following year, using data from electronic health records (EHRs), including both structured data and free-text progress notes. Methods: A cohort of adult glaucoma patients was identified from the EHR at Stanford University between 2008 and 2020, with data including free-text clinical notes, demographics, diagnosis codes, prior surgeries, and clinical information, including intraocular pressure, visual acuity, and central corneal thickness. Words from patients' notes were mapped to ophthalmology domain-specific neural word embeddings. Word embeddings and structured clinical data were combined as inputs to deep learning models to predict whether a patient would undergo glaucoma surgery in the following 12 months using the previous 4-12 months of clinical data. We also evaluated models using only structured data inputs (regression-, tree-, and deep-learning-based models) and models using only text inputs. Results: Of the 3,469 glaucoma patients included in our cohort, 26% underwent surgery. The baseline penalized logistic regression model achieved an area under the receiver operating curve (AUC) of 0.873 and F1 score of 0.750, compared with the best tree-based model (random forest, AUC 0.876; F1 0.746), the deep learning structured features model (AUC 0.885; F1 0.757), the deep learning clinical free-text features model (AUC 0.767; F1 0.536), and the deep learning model with both the structured clinical features and free-text features (AUC 0.899; F1 0.745). Discussion: Fusion models combining text and EHR structured data successfully and accurately predicted glaucoma progression to surgery. Future research incorporating imaging data could further optimize this predictive approach and be translated into clinical decision support tools.

Environmental Toxins and Alzheimer's Disease: a Comprehensive Analysis of Pathogenic Mechanisms and Therapeutic Modulation.

Alzheimer's disease is a leading cause of mortality worldwide. Inorganic and organic hazards, susceptibility to harmful metals, pesticides, agrochemicals, and air pollution are major environmental concerns. As merely 5% of AD cases are directly inherited indicating that these environmental factors play a major role in disease development. Long-term exposure to environmental toxins is believed to progress neuropathology, which leads to the development of AD. Numerous in-vitro and in-vivo studies have suggested the harmful impact of environmental toxins at cellular and molecular level. Common mechanisms involved in the toxicity of these environmental pollutants include oxidative stress, neuroinflammation, mitochondrial dysfunction, abnormal tau, and APP processing. Increased expression of GSK-3ß, BACE-1, TNF-α, and pro-apoptotic molecules like caspases is observed upon exposure to these environmental toxins. In addition, the expression of neurotrophins like BDNF and GAP-43 have been found to be reduced as a result of toxicity. Further, modulation of signaling pathways involving PARP-1, PGC-1α, and MAPK/ERK induced by toxins have been reported to contribute in AD pathogenesis. These pathways are a promising target for developing novel AD therapeutics. Drugs like epigallocatechin-gallate, neflamapimod, salsalate, dexmedetomidine, and atabecestat are in different phases of clinical trials targeting the pathways for possible treatment of AD. This review aims to culminate the correlation between environmental toxicants and AD development. We emphasized upon the signaling pathways involved in the progression of the disease and the therapeutics under clinical trial targeting the altered pathways for possible treatment of AD.

Endoplasmic reticulum stress in Alzheimer's disease: Molecular mechanisms and therapeutic prospects.

Alzheimer's disease (AD) is a progressive neurodegenerative condition that leads to memory loss and cognitive impairment over time. It is characterized by protein misfolding as well as prolonged cellular stress, such as perturbing calcium homeostasis and redox management. Numerous investigations have proven that endoplasmic reticulum failure may exhibit exacerbation of AD pathogenesis in AD patients, in-vivo and in-vitro models. The endoplasmic reticulum (ER) participates in a variety of biological functions including folding of protein, quality control, cholesterol production, and maintenance of calcium balance. A diverse range of physiological, pathological and pharmacological substances can interfere with ER activity and thus lead to exaggeration of ER stress. The unfolded protein response (UPR), an intracellular signaling network is stimulated due to ER stress. Three stress sensors found in the endoplasmic reticulum, the PERK, ATF6, and IRE1 transducers detect protein misfolding in the ER and trigger UPR, a complex system to maintain homeostasis. ER stress is linked to many of the major pathological processes that are seen in AD, including presenilin1 and 2 (PS1 and PS2) gene mutation, tau phosphorylation and ß-amyloid formation. The role of ER stress and UPR in the pathophysiology of AD implies that they can be employed as potent therapeutic target. This study shows the relationship between ER and AD and how the pathogenesis of AD is influenced by the impact of ER stress. An effective method for the prevention or treatment of AD may involve therapeutic strategies that modify ER stress pathways.

Oxidative Stress Enzyme as Markers in Oral Potentially Malignant Disorders and Oral Squamous Cell Carcinoma Patients.

Oxidative stress is a recognized factor that poses a significant risk for the development of Oral Squamous Cell Carcinoma (OSCC) and Oral Submucous Fibrosis (OSMF), as it leads to the generation of Reactive Oxygen Species. In recent years, there has been significant research on the enzymes MDA (malondialdehyde) and SOD (superoxide dismutase), investigating their potential role in the development of OPMD and OSCC. These enzymes have emerged as promising biomarkers due to their ability to provide a less invasive, cost-effective, and objective diagnostic method. Furthermore, they can be used to monitor disease progression and assess the effectiveness of therapy. The aim of this study was to assess the levels of MDA and SOD in the serum of patients diagnosed with OSCC and OSMF. Study group comprised of 60 patients, out of which 20 cases of clinically diagnosed OSCC patients and 20 cases of OSMF and 20 cases pf control comprising of healthy patients were recruited. Estimation MDA and SOD was done by ELISA. The statistical analysis was done using SPSS analysis. When comparing the levels of MDA and SOD between the OSCC and OSMF groups and the control group, statistically significant findings indicated elevated levels of malondialdehyde and reduced levels of superoxide dismutase in both the OSCC and OSMF groups. In this study, the assessment of lipid peroxidation through MDA levels revealed elevated concentrations in both the OSCC and OSMF groups when compared to the control group. Specifically, the order of MDA levels was observed as OSCC > OSMF > Control. Conversely, antioxidant enzyme levels, such as SOD, exhibited decreased concentrations in the OSCC and OSMF groups compared to the control group, with the order of SOD levels being Control > OSMF > OSCC. Consequently, the findings suggest that MDA and SOD can be considered potential biomarkers for identifying and monitoring OSCC and OSMF diseases.

Therapeutic role of N-acetyl cysteine (NAC) for the treatment and/or management of SARS-CoV-2-induced lung damage in hamster model.

Oxidative stress by reactive oxygen species (ROS) has been hypothesized to be the major mediator of SARS-CoV-2-induced pathogenesis. During infection, the redox homeostasis of cells is altered as a consequence of virus-induced cellular stress and inflammation. In such scenario, high levels of ROS bring about the production of pro-inflammatory molecules like IL-6, IL-1ß, etc. that are believed to be the mediators of severe COVID-19 pathology. Based on the known antioxidant, anti-inflammatory, mucolytic and antiviral properties of NAC, it has been hypothesized that NAC will have beneficial effects in COVID-19 patients. In the current study efforts have been made to evaluate the protective effect of NAC in combination with remdesivir against SARS-CoV-2 induced lung damage in the hamster model. The SARS-CoV-2 infected animals were administered with high (500 mg/kg/day) and low (150 mg/kg/day) doses of NAC intraperitoneally with and without remdesivir. Lung viral load, pathology score and expression of inflammatory molecules were checked by using standard techniques. The findings of this study show that high doses of NAC alone can significantly suppress the SARS-CoV-2 mediated severe lung damage (2 fold), but on the contrary, it fails to restrict viral load. Moreover, high doses of NAC with and without remdesivir significantly suppressed the expression of pro-inflammatory genes including IL-6 (4.16 fold), IL-1ß (1.96 fold), and TNF-α (5.55 fold) in lung tissues. Together, results of this study may guide future preclinical and clinical attempts to evaluate the efficacy of different doses and routes of NAC administration with or without other drugs against SARS-CoV-2 infection.

In vivo biocompatibility of ZIF-8 for slow release via intranasal administration.

Zeolitic imidazolate framework-8 (ZIF-8) is becoming popular in research for its potential in antigen protection and for providing a thermally stable, slow-release platform. While papers applying this material for immunological applications are aplenty in the literature, studies that explore the biosafety of ZIF-8 in mammals-especially when administered intranasally-are not well represented. We checked the body clearance of uncoated and ZIF-8-coated liposomes and observed that the release slowed as ZIF-8 is easily degraded by mucosal fluid in the nasal cavity. We delivered varying doses of ZIF-8, checked its short- and long-term effects on diagnostic proteins found in blood serum, and found no noticeable differences from the saline control group. We also studied their lung diffusing capacity and tissue morphology; neither showed significant changes in morphology or function.

Colchicine in the Management of Oral Submucous Fibrosis: A Systematic Review, Meta-analysis, and GRADE-Based Assessment of Certainty of Evidence.

Purpose: To study the efficacy of Colchicine in the management of Oral Sub mucous Fibrosis (OSMF) through systematic review and meta-analysis. Methods:An extensive literature search was conducted on databases such as PubMed, Cochrane Library database, LILACS, Google Scholar, CTRI, and Google search engine. The search comprises all articles published from 2013 to 2022. A total of 10 randomized control trial studies involving colchicine as one of the interventions were included. [CRD42022377674] Results:10 randomized control comprising 456 subjects were included. 3 studies are included in the meta-analysis comprising 90 subjects. All three studies show that there are significant differences between colchicine and other intervention regarding mouth opening and burning sensation. It indicates that Colchicine is significantly more effective in the reduction of burning sensation than other interventions used as a control in OSMF. Conclusion: The evidence generated through this systemic review and meta-analysis suggest that the use of an oral form of colchicine is an effective measure in the management of OSMF, especially the subjective symptom such as burning sensation where as it is not found to be much effective in case of mouth opening. If colchicine is used as co drug along with conventional injection therapy better will the result. However there is marked diversity among the studies reviewed; therefore, the results of this review should be interpreted very carefully.

Effect of counselling of parents of children with epilepsy focusing on sudden unexpected death in epilepsy.

OBJECTIVES: To characterize the effects of sudden unexpected death in epilepsy (SUDEP) counselling on epilepsy-related childcare behaviour and practices, and emotional distress, measured by the Depression, Anxiety and Stress scale-21 (DASS-21), among parents of children with epilepsy (CWE), and to obtain feedback about SUDEP counselling. METHODS: We conducted a single-arm, pre- and post-intervention study design. We enrolled 120 parents of CWE. At enrolment, we collected clinical and demographic data, assessed 18 epilepsy-related childcare and behaviour and practices and the DASS-21 score. Parents underwent a three-phase counselling, comprising SUDEP information via written material, followed by an informative video, and then a detailed face-to-face counselling session with treating clinicians. Changes in epilepsy-related childcare behaviour and practices, and DASS-21 scores were reassessed at one month. Qualitative feedback was obtained about SUDEP counselling. RESULTS: At one month, 84.2 % of parents reported a change in >2 epilepsy-related childcare behaviour and practices. Significant improvement compared to baseline was observed in reported administration of anti-seizure medications at fixed time (100 % versus 57.5 %; p < 0.0001), regular exercise (87.5 % versus 60 %; p < 0.0001), supervision of activity as advised (56.7-39.2 %; p = 0.0096), having a seizure action plan (97.5 % versus 20 %; p < 0.0001), rescue medications (95 % versus 25.8 %; p < 0.0001), providing information of child's epilepsy to schools (100 % versus 62 %; p < 0.0001), providing an emergency contact number in schools (100 % versus 58 %; p < 0.0001), and a seizure action plan in their child's school (54 % versus 8 %; p < 0.0001). There was no significant change in DASS-21 scores at one month. Parents expressed a preference for face-to-face interaction, in combination with other audiovisual modes, for SUDEP counselling, and being counselled when they were comfortable with their child's diagnosis of epilepsy. SIGNIFICANCE: SUDEP disclosure among Indian parents of CWE was associated with significant improvement in self-reported epilepsy-related childcare behaviour and practices, without increase in depression, stress or anxiety.

Rip it, stitch it, click it: A Chemist's guide to VLP manipulation.

Viruses are some of nature's most ubiquitous self-assembled molecular containers. Evolutionary pressures have created some incredibly robust, thermally, and enzymatically resistant carriers to transport delicate genetic information safely. Virus-like particles (VLPs) are human-engineered non-infectious systems that inherit the parent virus' ability to self-assemble under controlled conditions while being non-infectious. VLPs and plant-based viral nanoparticles are becoming increasingly popular in medicine as their self-assembly properties are exploitable for applications ranging from diagnostic tools to targeted drug delivery. Understanding the basic structure and principles underlying the assembly of higher-order structures has allowed researchers to disassemble (rip it), reassemble (stitch it), and functionalize (click it) these systems on demand. This review focuses on the current toolbox of strategies developed to manipulate these systems by ripping, stitching, and clicking to create new technologies in the biomedical space.