Green synthesis of metal nanoparticles and study their anti-pathogenic properties against pathogens effect on plants and animals.

According to an estimate, 30% to 40%, of global fruit are wasted, leading to post harvest losses and contributing to economic losses ranging from $10 to $100 billion worldwide. Among, all fruits the discarded portion of oranges is around 20%. A novel and value addition approach to utilize the orange peels is in nanoscience. In the present study, a synthesis approach was conducted to prepare the metallic nanoparticles (copper and silver); by utilizing food waste (Citrus plant peels) as bioactive reductants. In addition, the Citrus sinensis extracts showed the reducing activity against metallic salts copper chloride and silver nitrate to form Cu-NPs (copper nanoparticles) and Ag-NPs (Silver nanoparticles). The in vitro potential of both types of prepared nanoparticles was examined against plant pathogenic bacteria Erwinia carotovora (Pectobacterium carotovorum) and pathogens effect on human health Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). Moreover, the in vivo antagonistic potential of both types of prepared nanoparticles was examined by their interaction with against plant (potato slices). Furthermore, additional antipathogenic (antiviral and antifungal) properties were also examined. The statistical analysis was done to explain the level of significance and antipathogenic effectiveness among synthesized Ag-NPs and Cu-NPs. The surface morphology, elemental description and size of particles were analyzed by scanning electron microscopy, transmission electron microscopy, energy-dispersive spectroscopy and zeta sizer (in addition polydispersity index and zeta potential). The justification for the preparation of particles was done by UV-Vis Spectroscopy (excitation peaks at 339 nm for copper and 415 nm for silver) and crystalline nature was observed by X-ray diffraction. Hence, the prepared particles are quite effective against soft rot pathogens in plants and can also be used effectively in some other multifunctional applications such as bioactive sport wear, surgical gowns, bioactive bandages and wrist or knee compression bandages, etc.

A combination of gliclazide and metformin attenuates obesity-induced polycystic ovary syndrome in female Wistar rats.

Presently, it is known that the progression of obesity concomitantly leads to polycystic ovary syndrome and infertility. This study aimed to evaluate the potential effects of metformin (M; insulin secretagogues) and gliclazide (G; insulin sensitizer) alone and their combination at different doses to treat obesity-induced PCOS. High high-fat diet was given to all female Wistar rats for nine weeks to induce obesity except for the normal control group which received a normal chow diet. Estradiol valerate (0.8 mg/kg) was also given to all obese rats to induce polycystic ovarian syndrome. After the induction, M (100, 300 mg/kg) and G (5, 10 mg/kg) were given orally either individually or in combination for 28 days. The notable (p < 0.0001) reduction in body weight and blood glucose level was observed in treatment groups in contrast to disease control (DCG). The marked (p < 0.05-0.0001) decrease in hemocylated hemoglobin, serum insulin, cholesterol, triglycerides, and testosterone was observed in treated groups, notably in combination groups (M100+G10 mg/kg) in contrast to DCG. There was a considerable (p < 0.01-0.0001) increase in progesterone E2, estradiol, luteinizing, and follicle-stimulating hormones in treated groups as compared to DCG. Treatment with M and G treated groups also exhibited marked (p < 0.05-0.0001) increases in SOD, CAT, and GSH while decreased in NO and MDA levels in ovary tissue as evidenced by the histological study of the ovary. Treatment with M and G alone and in combination significantly (p < 0.0001) restored the serum IL-6, NrF2, and NF-κB levels as compared to DCG. The results inveterate that the M and G combination (M100+G10, and M300+G10) was useful in treating obesity-induced infertility due to antioxidant properties, hypolipidemic effects, and modulation of inflammatory markers.

Development of biomedical hydrogels for rheumatoid arthritis treatment.

Rheumatoid Arthritis (RA) is an autoimmune disorder that hinders the normal functioning of bones and joints and reduces the quality of human life. Every year, millions of people are diagnosed with RA worldwide, particularly among elderly individuals and women. Therefore, there is a global need to develop new biomaterials, medicines and therapeutic methods for treating RA. This will improve the Healthcare Access and Quality Index and also relieve administrative and financial burdens on healthcare service providers at a global scale. Hydrogels are soft and cross-linked polymeric materials that can store a chunk of fluids, drugs and biomolecules for hydration and therapeutic applications. Hydrogels are biocompatible and exhibit excellent mechanical properties, such as providing elastic cushions to articulating joints by mimicking the natural synovial fluid. Hence, hydrogels create a natural biological environment within the synovial cavity to reduce autoimmune reactions and friction. Hydrogels also lubricate the articulating joint surfaces to prevent degradation of synovial surfaces of bones and cartilage, thus exhibiting high potential for treating RA. This work reviews the progress in injectable and implantable hydrogels, synthesis methods, types of drugs, advantages and challenges. Additionally, it discusses the role of hydrogels in targeted drug delivery, mechanistic behaviour and tribological performance for RA treatment.

Development of mRNA nano-vaccines for COVID-19 prevention and its biochemical interactions with various disease conditions and age groups.

This review has focused on the development of mRNA nano-vaccine and the biochemical interactions of anti-COVID-19 mRNA vaccines with various disease conditions and age groups. It studied five major groups of individuals with different disease conditions and ages, including allergic background, infarction background, adolescent, and adult (youngsters), pregnant women, and elderly. All five groups had been reported to have background-related adverse effects. Allergic background individuals were observed to have higher chances of experiencing allergic reactions and even anaphylaxis. Individuals with an infarction background had a higher risk of vaccine-induced diseases, e.g. pneumonitis and interstitial lung diseases. Pregnant women were seen to suffer from obstetric and gynecological adverse effects after receiving vaccinations. However, interestingly, the elderly individuals (> 65 years old) had experienced milder and less frequent adverse effects compared to the adolescent (<19 and >9 years old) and young adulthood (19-39 years old), or middle adulthood (40-59 years old) age groups, while middle to late adolescent (14-17 years old) was the riskiest age group to vaccine-induced cardiovascular manifestations.

Current Updates on the Role of MicroRNA in the Diagnosis and Treatment of Neurodegenerative Diseases.

BACKGROUND: MicroRNAs (miRNA) are small noncoding RNAs that play a significant role in the regulation of gene expression. The literature has explored the key involvement of miRNAs in the diagnosis, prognosis, and treatment of various neurodegenerative diseases (NDD), such as Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD). The miRNA regulates various signalling pathways; its dysregulation is involved in the pathogenesis of NDD. OBJECTIVE: The present review is focused on the involvement of miRNAs in the pathogenesis of NDD and their role in the treatment or management of NDD. The literature provides comprehensive and cutting-edge knowledge for students studying neurology, researchers, clinical psychologists, practitioners, pathologists, and drug development agencies to comprehend the role of miRNAs in the NDD's pathogenesis, regulation of various genes/signalling pathways, such as α-synuclein, P53, amyloid-ß, high mobility group protein (HMGB1), and IL-1ß, NMDA receptor signalling, cholinergic signalling, etc. Methods: The issues associated with using anti-miRNA therapy are also summarized in this review. The data for this literature were extracted and summarized using various search engines, such as Google Scholar, Pubmed, Scopus, and NCBI using different terms, such as NDD, PD, AD, HD, nanoformulations of mRNA, and role of miRNA in diagnosis and treatment. RESULTS: The miRNAs control various biological actions, such as neuronal differentiation, synaptic plasticity, cytoprotection, neuroinflammation, oxidative stress, apoptosis and chaperone-mediated autophagy, and neurite growth in the central nervous system and diagnosis. Various miRNAs are involved in the regulation of protein aggregation in PD and modulating ß-secretase activity in AD. In HD, mutation in the huntingtin (Htt) protein interferes with Ago1 and Ago2, thus affecting the miRNA biogenesis. Currently, many anti-sense technologies are in the research phase for either inhibiting or promoting the activity of miRNA. CONCLUSION: This review provides new therapeutic approaches and novel biomarkers for the diagnosis and prognosis of NDDs by using miRNA.

Late-onset pulmonary complications among survivors of coronavirus Disease 2019.

Objectives: To assess the late-onset pulmonary complications among survivors of coronavirus disease 2019. Methods: The cross-sectional analytical study was conducted in the department of Pulmonology, Sir Ganga Ram Hospital Lahore between October 2020 and March 2021. Total 288 patients visiting the hospital 12-week after recovery from COVID-19 enrolled using convenience sampling. After excluding patients (n=61) with a history of previous respiratory symptoms before the development of COVID-19, data from 227 patients was subjected to final analysis. Chest X-ray (CXR) was used to evaluate lung condition. Results: Participation of middle-aged adults (54.6%) was higher than older (38.3%) and young adults (7.0%). The percentage of males was 55.5% and smokers was 29.1%. Dyspnea was the most common complication as 80.0% patients had moderate to severe dyspnea while chronic cough was 78.0% and lung fibrosis (LF) was 13.2%. The chances of LF increased with the rise in age (p-value 0.033). However, the distribution of LF was similar between males and females. The frequency of lung fibrosis in smokers was 3-time higher than among non-smokers (24.2 vs. 8.7%; p-value 0.003). The patients with LF were more dependent on O2 as compared to the patients without LF (p-value < 0.001). The frequency of tachycardia was significantly different between patients with and without LF (all p-values < 0.05). Conclusion: LF is a common late-onset pulmonary complication of COVID-19 and is associated with old age, smoking, O2 dependency, tachycardia, and severe dyspnea.

Micro- and nanoplastics: Contamination routes of food products and critical interpretation of detection strategies.

Micro-and nanoplastics (M/NPs) are emerging pollutants released into the food, beverages, and environment from plastic products by weathering, oxidative damage, and mechanical stress. Detection of M/NPs in food and beverages is a vital factor in preventing the deleterious effects of these materials on human health and other ecosystems. Analytical strategies for M/NPs demonstrate numerous drawbacks, including detection sensitivity limitation, matrix digestion, and sample pretreatment. Moreover, the content of M/NPs in food and beverages varies with food production, storage, and transport, making it hard to precisely detect them. The contamination route is a key factor affecting the level of M/NPs in food and beverages. Strict control over the contamination route could be beneficial in preventing M/NP pollution. This review highlighted routes of food and beverage contamination by M/NPs, various pros and cons of detection strategies, and critical interpretation of reported techniques, including microscopy, spectroscopy, light scattering, and thermal methods. Besides, the bottlenecks of detection and quantification approaches for M/NPs and recent advancements have also been highlighted. Much is still unknown concerning the fate, activities, and properties of M/NPs present in various matrices. This review aims to assist the investigators to tackle the drawbacks and pave the way for upcoming research, minimizing the health complications by regulating the control over M/NPs pollution.

Exploring the robustness of DNA nanotubes framework for anticancer theranostics toward the 2D/3D clusters of hypopharyngeal respiratory tumor cells.

This study aimed to develop a robust approach for the early diagnosis and treatment of tumors. Short circular DNA nanotechnology synthesized a stiff and compact DNA nanotubes (DNA-NTs) framework. TW-37, a small molecular drug, was loaded into DNA-NTs for BH3-mimetic therapy to elevate the intracellular cytochrome-c levels in 2D/3D hypopharyngeal tumor (FaDu) cell clusters. After anti-EGFR functionalization, the DNA-NTs were tethered with a cytochrome-c binding aptamer, which can be applied to evaluate the elevated intracellular cytochrome-c levels via in situ hybridization (FISH) analysis and fluorescence resonance energy transfer (FRET). The results showed that DNA-NTs were enriched within the tumor cells via anti-EGFR targeting with a pH-responsive controlled release of TW-37. In this way, it initiated the triple inhibition of "BH3, Bcl-2, Bcl-xL, and Mcl-1". The triple inhibition of these proteins caused Bax/Bak oligomerization, leading to the perforation of the mitochondrial membrane. This led to the elevation of intracellular cytochrome-c levels, which reacted with the cytochrome-c binding aptamer to produce FRET signals. In this way, we successfully targeted 2D/3D clusters of FaDu tumor cells and achieved the tumor-specific and pH-triggered release of TW-37, causing tumor cell apoptosis. This pilot study suggests that anti-EGFR functionalized, TW-37 loaded, and cytochrome-c binding aptamer tethered DNA-NTs might be the hallmark for early tumor diagnosis and therapy.

Risk factors of previously undiagnosed and known untreated hypertension among patients with Type-2 diabetes mellitus.

Objectives: To find the risk factors of previously undiagnosed and known untreated hypertension among patients with Type- 2 diabetes mellitus. Methods: The cross-sectional analytical study was conducted at Diabetes Clinic of Sir Ganga Ram Hospital Lahore during Oct-Dec 2021. Total 153 known diabetics were enrolled using convenience sampling. Patients (n=24) with ischemic heart disease, hepatitis or missing information excluded. Data from 129 cases of Type-2 diabetes presenting with and without hypertension analyzed using SPSS. Binary logistic regression analyses were performed to calculate the adjusted odds ratios. Result: Mean age of all diabetics (n=129) was 49.0±10.7 years. The participation of females was higher than males (65.1% vs. 34.9%). The frequency of hypertension, previously undiagnosed hypertension and known untreated hypertension was 58.1%, 25.3% and 19.6%, respectively. Among risk factors, frequency of high intake of salt was 67.4%, sedentary lifestyle was 65.1%, obesity was 37.2%, and poor glycemic control was 58.9%. Young age [aOR=2.01, 95.0% CI 0.53-7.61], low family income <20000 PKR/month [aOR=2.70, 95.0% CI 0.92-7.96], high intake of salt [aOR=3.22, 95.0% CI 0.98-10.61], elevated total cholesterol [aOR=3.68, 95.0% CI 0.85-15.85], poor glycemic control [aOR=3.28, 95.0% CI 0.51-21.13], and overweight/ obesity [aOR=9.07, 95.0% CI 1.6-51.39] had higher risk of previously undiagnosed or known untreated HTN. Conclusions: Prevalence of previously undiagnosed and known untreated hypertension is high among Type-2 diabetics. Strict compliance to diabetes care guidelines is much needed to minimize the risk of undiagnosed and untreated hypertension.

Hepatoprotective effect of Cordia rothii extract against CCl4-induced oxidative stress via Nrf2-NFκB pathways.

Cordia rothii Roem. & Schult. possesses various beneficial effects and is traditionally used in folk medicine against liver diseases but its molecular mechanism remains unclear. Antioxidant and hepatoprotective effects of Cordia rothii methanolic fraction (CRMF) were investigated in CCl4-induced liver injury. Antioxidant effects were evaluated using DPPH assay, ferric thiocyanate (FTC) assay, and HepG2 cells. A qualitative analysis of phytochemicals was carried out by gas chromatography-mass spectrometry (GC-MS). The hepatoprotective effects of CRMF were assessed against CCl4-induced liver damage in rats. Our results showed that CRMF significantly increased cell viability against CCl4-induced HepG2 cells. The in vivo results showed that CRMF significantly reduced the level of aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), total bilirubin, hepatic antioxidant enzymes, including superoxide dismutase, malondialdehyde, and increased glutathione level. Normal hepatocyte integrity and microstructures were observed in histopathological results. Furthermore, the mRNA level of inflammatory mediators including interleukon (IL)-1ß, IL-6, TNF-α, nuclear factor kappa B (NF-KB), IL-10 and nuclear factor-erythroid factor 2-related factor 2 (NrF2) were reverted in CRMF pretreatment groups. Thus, CRMF exhibited strong antioxidant, and hepatoprotective activities, which may involve Nrf2-NFκB pathways.

Disrupting biofilm and eradicating bacteria by Ag-Fe3O4@MoS2 MNPs nanocomposite carrying enzyme and antibiotics.

In this study, novel multilayered magnetic nanoparticles (ML-MNPs) loaded with DNase and/or vancomycin (Vanc) were fabricated for eliminating multispecies biofilms. Iron-oxide MNPs (IO-core) (500-800 nm) were synthesized via co-precipitation; further, the IO-core was coated with heavy-metal-based layers (Ag and MoS2 NPs) using solvent evaporation. DNase and Vanc were loaded onto the outermost layer of the ML-MNP formed by nanoporous MoS2 NPs through physical deposition and adsorption. The biofilms of S. mutans or E. faecalis (or both) were formed in a brain-heart-infusion broth (BHI) for 3 days, followed by treatment with ML-MNPs for 24 h. The results revealed that coatings of Ag (200 nm) and ultrasmall MoS2 (20 nm) were assembled as outer layers of ML-MNPs successfully, and they formed Ag-Fe3O4@MoS2 MNPs (3-5 µm). The DNase-Vanc-loaded MNPs caused nanochannels digging and resulted in the enhanced penetration of MNPs towards the bottom layers of biofilm, which resulted in a decrease in the thickness of the 72-h biofilm from 48 to 58 µm to 0-4 µm. The sustained release of Vanc caused a synergistic bacterial killing up to 96%-100%. The heavy-metal-based layers of MNPs act as nanozymes to interfere with bacterial metabolism and proliferation, which adversely affects biofilm integrity. Further, loading DNase/Vanc onto the nanoporous-MoS2-layer of ML-MNPs promoted nanochannel creation through the biofilm. Therefore, DNase-and Vanc-loaded ML-MNPs exhibited potent effects on biofilm disruption and bacterial killing.

Corrigendum to "The effective transfection of a low dose of negatively charged drug-loaded DNA-nanocarriers into cancer cells via scavenger receptors"[Journal of Pharmaceutical Analysis volume 11 (2021) 174-182].

[This corrects the article DOI: 10.1016/j.jpha.2020.10.003.].

Nanoscale packing of DNA tiles into DNA macromolecular lattices.

Nanoscale double-crossovers (DX), antiparallel (A), and even half-turns-perimeter (E) DNA tiles (DAE-tiles) with rectangular shapes can be packed into large arrays of micrometer-scale lattices. But the features and mechanical strength of DNA assembly made from differently shaped large-sized DAE DNA tiles and the effects of various geometries on the final DNA assembly are yet to be explored. Herein, we focused on examining DNA lattices synthesized from DX bi-triangular, DNA tiles (T) with concave and convex regions along the perimeter of the tiles. The bi-triangular DNA tiles "T(A) and T(B)" were synthesized by self-assembling the freshly prepared short circular scaffold (S) strands "S(A) and S(B)", each of 106 nucleotides (NT) lengths. The tiles "T(A) and T(B)" were then coupled together to get assembled via sticky ends. It resulted in the polymerization of DNA tiles into large-sized DNA lattices with giant micrometer-scale dimensions to form the "T(A) + T(B)" assembly. These DNA macro-frameworks were visualized "in the air" under atomic force microscopy (AFM) employing tapping mode. We have characterized how curvature in DNA tiles may undergo transitions and transformations to adjust the overall torque, strain, twists, and the topology of the final self-assembly array of DNA tiles. According to our results, our large-span DX tiles assembly "T(A) + T(B)" despite the complicated curvatures and mechanics, was successfully packed into giant DNA lattices of the width of 30-500 nm and lengths of 500 nm to over 10 µm. Conclusively, the micrometer-scale "T(A) + T(B)" framework assembly was rigid, stable, stiff, and exhibited enough tensile strength to form monocrystalline lattices.

Nanostructured Lipid Carrier-Based Delivery of Pioglitazone for Treatment of Type 2 Diabetes.

Pioglitazone (PGZ) is utilized as a therapeutic agent in the management of (type 2) diabetes to control blood glucose levels. The existing research work was intended to make and optimize PGZ-containing NLCs (nanostructured lipid carriers). The fabricated nanostructured lipid carrier preparation was optimized by using different concentrations of the surfactants (Tween 80 and Span 80) and solid lipid (Compritol® 888 ATO) and liquid lipid (Labrasol®) while keeping the concentration of drug (PGZ), and co-surfactants (poloxamer 188) the same. The optimized NLC formulation (PGZ-NLCs) was further assessed for physical and chemical characterization, in vitro PGZ release, and stability studies. The optimized PGZ-NLCs have shown an average diameter of 150.4 nm, EE of 92.53%, PDI value of 0.076, and zeta-potential of -29.1 mV, correspondingly. The DSC thermal analysis and XRD diffractograms had not presented the spectrum of PGZ, confirming the comprehensive encapsulation of PGZ in the lipid core. PGZ-NLCs showed significantly extended release (51% in 24 h) compared to the unformulated PGZ. Our study findings confirmed that PGZ-NLCs can be a promising drug delivery system for the treatment of type 2 diabetes.

Application Perspectives of Nanomedicine in Cancer Treatment.

Cancer is a disease that seriously threatens human health. Based on the improvement of traditional treatment methods and the development of new treatment modes, the pattern of cancer treatment is constantly being optimized. Nanomedicine plays an important role in these evolving tumor treatment modalities. In this article, we outline the applications of nanomedicine in three important tumor-related fields: chemotherapy, gene therapy, and immunotherapy. According to the current common problems, such as poor targeting of first-line chemotherapy drugs, easy destruction of nucleic acid drugs, and common immune-related adverse events in immunotherapy, we discuss how nanomedicine can be combined with these treatment modalities, provide typical examples, and summarize the advantages brought by the application of nanomedicine.

Efficacy And Safety Of Intravenous Iron In Children With Iron Deficiency Anaemia Poorly Compliant To Oral Iron Therapy.

BACKGROUND: Iron deficiency is the most common nutritional deficiency worldwide. Common causes of IDA in children are excessive consumption of cow's milk and prolonged breast feeding with delayed and poor weaning. Oral iron is the first line of treatment in children with IDA but occasionally there is inadequate response due to poor compliance. The objective of this study is to assess the effectiveness and safety of intravenous iron in children with IDA, poorly compliant to oral iron therapy. Methods: This study consisted of 90 children from 12-60 months with IDA who were not responding adequately to oral iron therapy. Total iron requirement was calculated and given intravenously (IV) in two divided doses over two consecutive days. Participants were followed up at 2 and 4 weeks to assess the rise in haemoglobin level. Any adverse event was also noted. SPSS version 25 was used for statistical analysis. RESULTS: Of the 90 enrolled children the mean age was 23.1±10.7 months, 47 (52.2%) were males and 43(47.8%) were females. The mean ferritin level before IV iron therapy was 3.75±2.53 ng/ml and mean haemoglobin was 5.9±1.3 g/dL. After IV iron therapy the haemoglobin level was raised to 8.38±1.09 g/dl and 9.74±0.88 g/dl at 2 and 4 weeks respectively which was statistically significant (p<0.05). The adverse events were fever in 3 (3.3%) and urticaria in 2 (2.2%) patients. CONCLUSIONS: Intravenous iron therapy is effective and safe to raise the haemoglobin levels in children with IDA who are poorly compliant to oral iron therapy.