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Objectives To investigate the occurrence and molecular features of ESBL-producing and colistin-resistant Escherichia coli isolates recovered from healthy food-producing animals in Pakistan. Methods A total of 153 E. coli isolates were recovered from 250 faecal samples collected from livestock and poultry. The antibiotic susceptibility, resistant determinants and mobile genetic elements were determined for all the isolates. The clonal relatedness was analysed by MLST. Plasmids harbouring, localization and transferability of mcr-1 gene were carried out by Southern hybridization, S1-PFGE and transconjugation. Results Out of 153 E. coli strains, 49.01% isolates were ESBLs producers, whereas 18.95% were resistant to colistin and 84.31% of the isolates. Multidrug resistance was found in 84% of the isolates. The ESBL-producing E. coli in buffaloes, cattle, sheep, goat and broilers faecal samples were 60%, 74%, 54%, 50% and 68%, respectively. Among the ESBLs genes, blaCTX-M was the most prevalent group detected in 98.66%, while only mcr-1 of the colistin-resistant genes could be PCR amplified in 29 isolates. The common MGEs found were ISECP1 (35.13%), ISCR1 (33.78%), ISApl1 (20.27%) and Inti1 (58.10%). The most predominant Inc. types found were IncFIB 46.66%, followed by IncFIA 30.66%, IncFIC 26.66%, IncFrepB 26.66%, IncHI2 26.66%, IncP 22.66% and IncX4 21.33%. The most frequent sequence type detected was ST58. Southern blot and S1-PFGE confirmed the plasmid harbouring of mcr-1 gene. Conclusion The co-occurrence of mcr-1 and ESBLs-encoding genes, along with MGEs in E. coli from healthy food animals in Pakistan, is a major concern. Significance and Impact of Study Antimicrobial resistance can be transferred from animals to humans by direct contact or via the food chain and environment. The prevalence and co-occurrence of ESBL and colistin resistance genes from food-producing animals is rare in Pakistan. To our knowledge, this is the first report to find ESBLs and mcr-1-harbouring E. coli from the faecal samples of the healthy food-producing animals in Pakistan. The presence of ARGs in association with MGEs, co-harbouring the virulence factors, as determined in the current study, is a severe threat to livestock and the human community as it has horizontally and food web transferability.

Polycations have a high siRNA binding efficiency, however, their cytotoxicity and poor transfection efficiency prevent their use in siRNA delivery. This study combined PEGylation for enhanced safety with a photothermally controlled endolysosomal escape to improve the cytoplasmic delivery of polycations.We first synthesized PEGylated cationic polymers (denoted as PEG-PHD), which were then used to prepare polyplexes with siRNA and ICG through electrostatic interactions. We found that the cytotoxicity of PEG-PHD and its polyplexes were significantly decreased compared with unPEGylated PHD. The prepared polyplexes successfully induced endolysosomal escape under laser irradiation, thereby showing better siRNA delivery efficiency in vitro and in vivo. Finally, polyplexes carrying siBcl-2 achieved significant inhibition of 4T1 tumor mediated by specific gene silencing after intravenous injection. In conclusion, this biocompatible photothermal controlled delivery platform is suitable for improving the efficiency of siRNA transfection. Overall, this study suggests that combing PEGylation and photoresponsive delivery is a promising strategy for designing siRNA delivery carriers.

The delivery of therapeutic cancer agents via nanomaterials has received significant attention. However, because of the absence of tumour targeting, tumour treatment strategies are still not satisfactory. Umbilical cord mesenchymal stem cells are inherently prone to migrate to malignant sites, enabling them to deliver antitumour drugs effectively. Therefore, it is expected to be a promising tool for tumour targeting. In this study, we constructed magnetic drug-loaded nanoparticles comprised of ferroferric oxide and doxorubicin, which were ingested by umbilical cord mesenchymal stem cells and precisely delivered to the tumour sites. Here, we physicochemically characterized the nanoparticles for the particle size, biocompatibility and cellular uptake. The umbilical cord mesenchymal stem cells migration and homing ability before and after drug loading were evaluated. The anti-cancer effect of stem cells loaded with nanoparticles was determined using MCF-7 cells. In vitro studies, the magnetic drug-loaded nanoparticles complex on tumour cells revealed that umbilical cord mesenchymal stem cells could transport magnetic drug-loaded nanoparticles to induce robust apoptosis.

Liver fibrosis results from excessive extracellular matrix accumulation due to injury and leads to cirrhosis, cancer, and death. Herein, we propose a chemokine receptor 4 (CXCR4)-targeted combination (CTC) liposomal therapy to treat carbon tetrachloride (CCl

Cancer cases have reached an all-time high in the current era.

Aftab Ullah,1 Gang Chen,2 Abid Hussain,3,4 Hanif Khan,1 Azar Abbas,5 Zhanwei Zhou,5 Muhammad Shafiq,6 Saleem Ahmad,7 Usman Ali,8 Muhammad Usman,6 Faisal Raza,8 Abrar Ahmed,8 Zijie Qiu,5 Maochao Zheng,1 Daojun Liu1 1Department of Pharmacy, Shantou University Medical College, Shantou, 515041, Guangdong, People’s Republic of China; 2Institute of Comparative Medicine, College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu, People’s Republic of China; 3School of Life Science, Key Laboratory of Molecular Medicine and Biotherapy, Beijing Institute of Technology, Beijing, 100081, People’s Republic of China; 4Chinese Academy of Sciences (CAS) Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing, 100190, People’s Republic of China; 5School of Pharmacy, China Pharmaceutical University, Nanjing, 210028, Jiangsu, People’s Republic of China; 6Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong, 515041, people’s Republic of China; 7Department of Medicine, Shantou University Medical College Cancer Hospital, Shantou, People’s Republic of China; 8School of Pharmacy, Shanghai Jiaotong University, Shanghai, 200240, Shanghai, People’s Republic of ChinaCorrespondence: Aftab Ullah; Daojun Liu Email aftab@stu.edu.cn; liudj@stu.edu.cnBackground: Liver fibrosis is a chronic liver disease with excessive production of extracellular matrix proteins, leading to cirrhosis, hepatocellular carcinoma, and death.Purpose: This study aimed at the development of a novel derivative of polyethyleneimine (PEI) that can effectively deliver transforming growth factor β (TGFβ) siRNA and inhibit chemokine receptor 4 (CXCR4) for TGFβ silencing and CXCR4 Inhibition, respectively, to treat CCl4-induced liver fibrosis in a mouse model.Methods: Cyclam-modified PEI (PEI-Cyclam) was synthesized by incorporating cyclam moiety into PEI by nucleophilic substitution reaction. Gel electrophoresis confirmed the PEI-Cyclam polyplex formation and stability against RNAase and serum degradation. Transmission electron microscopy and zeta sizer were employed for the morphology, particle size, and zeta potential, respectively. The gene silencing and CXCR4 targeting abilities of PEI-Cyclam polyplex were evaluated by luciferase and CXCR4 redistribution assays, respectively. The histological and immunohistochemical staining determined the anti-fibrotic activity of PEI-Cyclam polyplex. The TGFβ silencing of PEI-Cyclam polyplex was authenticated by Western blotting.Results: The 1H NMR of PEI-Cyclam exhibited successful incorporation of cyclam content onto PEI. The PEI-Cyclam polyplex displayed spherical morphology, positive surface charge, and stability against RNAse and serum degradation. Cyclam modification decreased the cytotoxicity and demonstrated CXCR4 antagonistic and luciferase gene silencing efficiency. PEI-Cyclam/siTGFβ polyplexes decreased inflammation, collagen deposition, apoptosis, and cell proliferation, thus ameliorating liver fibrosis. Also, PEI-Cyclam/siTGFβ polyplex significantly downregulated α-smooth muscle actin, TGFβ, and collagen type III.Conclusion: Our findings validate the feasibility of using PEI-Cyclam as a siRNA delivery vector for simultaneous TGFβ siRNA delivery and CXCR4 inhibition for the combined anti-fibrotic effects in a setting of CCl4-induced liver fibrosis.Keywords: polyethyleneimine, cyclam, gene delivery, liver fibrosis, CXCR4

An appropriate delivery system can improve the immune effects of antigens against various infections or tumors. Antigen-presenting cells (APCs) are specialized to capture and process antigens in vivo, which link the innate and adaptive immune responses. Functionalization of vaccine delivery systems with targeting moieties to APCs is a promising strategy for provoking potent immune responses. Additionally, the internalization and intracellular distribution of antigens are closely related to the initiation of downstream immune responses. With a deeper understanding of the intracellular microenvironment and the mechanisms of antigen presentation, vehicles designed to respond to endogenous and external stimuli can modulate antigen processing and presentation pathways, which are critical to the types of immune response. Here, an overview of extracellular targeting delivery of antigens to APCs and intracellular stimulus-responsiveness strategies is provided, which might be helpful for the rational design of vaccine delivery systems.

Plants are a major source of food for the world population. Plant diseases contribute to production loss, which can be tackled with continuous monitoring. Manual plant disease monitoring is both laborious and error-prone. Early detection of plant diseases using computer vision and artificial intelligence (AI) can help to reduce the adverse effects of diseases and also overcome the shortcomings of continuous human monitoring. In this work, we propose the use of a deep learning architecture based on a recent convolutional neural network called EfficientNet on 18,161 plain and segmented tomato leaf images to classify tomato diseases. The performance of two segmentation models i.e., U-net and Modified U-net, for the segmentation of leaves is reported. The comparative performance of the models for binary classification (healthy and unhealthy leaves), six-class classification (healthy and various groups of diseased leaves), and ten-class classification (healthy and various types of unhealthy leaves) are also reported. The modified U-net segmentation model showed accuracy, IoU, and Dice score of 98.66%, 98.5%, and 98.73%, respectively, for the segmentation of leaf images. EfficientNet-B7 showed superior performance for the binary classification and six-class classification using segmented images with an accuracy of 99.95% and 99.12%, respectively. Finally, EfficientNet-B4 achieved an accuracy of 99.89% for ten-class classification using segmented images. It can be concluded that all the architectures performed better in classifying the diseases when trained with deeper networks on segmented images. The performance of each of the experimental studies reported in this work outperforms the existing literature. 2021 by the authors. Licensee MDPI, Basel, Switzerland. Funding: The open-access publication of this article was funded by the Qatar National Library and this work was made possible by HSREP02-1230-190019 from the Qatar National Research Fund, a member of Qatar Foundation, Doha, Qatar. The statements made herein are solely the responsibility of the authors. Scopus

Background: Acute pancreatitis is a common health issue that leads to emotional, physical and financial human burden. Aim: To determine the diagnostic accuracy of CTSI, in predicting the severity of acute pancreatitis, keeping Ranson’s score as Gold Standard. Study design: Cross Sectional study. Methodology: Total of 148 patients were observed by using Sajid’s calculator for sensitivity and specificity, using a sensitivity of 87.5% with a margin of error = 10% and a specificity of 55.3% with a margin of error=10%, with a confidence interval of 95% and a prevalence rate of 20%. Moreover, random consecutive sampling technique was used for sample collection. Data was evaluated by using SPSS version 24. The results were presented as counts (percentage), means and, standard deviation as appropriate. Results: Our study showed that mean age was 42 years with SD±2.25. Twenty eight percent patients were male, 107(72%) patients were female. Diagnostic accuracy of CTSI score keeping Ranson’s score as a gold standard was analyzed as CTSI has the sensitivity 91%, Specificity 59%. Positive predictive value was 81%, Negative predictive value 67%, Diagnostic accuracy was 84%. Practical Implication: The routine use of CTSI has been practiced in our health setup since long but not much research was done to assess the validity of CTSI in our population. Thus present study assessed the effectiveness of CTSI in our population against the local standard validates in our local setup. Conclusion: It was concluded that CT severity index is still a very valuable and relatively inexpensive tool for assessing acute inflammation of pancreas and for predicting the severity of the pancreatitis. Keywords: Diagnostic Accuracy, CTSI, Acute Pancreatitis and Ranson’s Score.

Background: Fistula-in-ano is an abnormal tract that usually connects rectal mucosa and perianal skin thus accounting upto 90% cases with an incidence of 5.6/100.000 in women while 12.3/100.000 in men. Aim: To determine the frequency of healing in patients with high lying fistlua in ano undergoing VAAFT. Study design: Cross-sectional study. Methodology: Patients (n=153) were enrolled during study. All enrolled patients had DRE and proctoscopy before start of treatment. Fistuloscope was used to diagnose high lying fistula during examination. Metronidazole antibiotic was given to all patients both pre and post-surgery. SPSS v.26 analyzed the data. Stratification of healing data was done with respect to age and gender. Post stratification Chi-Squire test was applied with P-value ≤0.05 was taken as significant. Results: Almost 77% were males while rest (23%) patients were females. Results showed healing in 70% of patients while 30% patients failed to heal. Practical Implication: This study showed that VAAFT procedure is safe as a treatment modality in comparison to Anal Fistula Plug and conventional Seton placement for complex fistulas or high anal fistulas thus advocated sphincter saving procedure in our setups. Conclusion: It was concluded that this new surgical technique has advantages like sphincter-saving with small surgical wounds. However, fistuloscopy identifies secondary tracts or chronic abscesses. Keywords: Healing, High Lying Fistlua and VAAFT.

Plants are a major source of food for the world population. Plant diseases contribute to production loss, which can be tackled with continuous monitoring. Manual plant disease monitoring is both laborious and error-prone. Early detection of plant diseases using computer vision and artificial intelligence (AI) can help to reduce the adverse effects of diseases and also helps to overcome the shortcomings of continuous human monitoring. In this study, we have extensively studied the performance of the different state-of-the-art convolutional neural networks (CNNs) classification network architectures i.e. ResNet18, MobileNet, DenseNet201, and InceptionV3 on 18,162 plain tomato leaf images to classify tomato diseases. The comparative performance of the models for the binary classification (healthy and unhealthy leaves), six-class classification (healthy and various groups of diseased leaves), and ten-class classification (healthy and various types of unhealthy leaves) are also reported. InceptionV3 showed superior performance for the binary classification using plain leaf images with an accuracy of 99.2%. DenseNet201 also outperform for six-class classification with an accuracy of 97.99%. Finally, DenseNet201 achieved an accuracy of 98.05% for ten-class classification. It can be concluded that deep architectures performed better at classifying the diseases for the three experiments. The performance of each of the experimental studies reported in this work outperforms the existing literature.

How triptolide is associated with mitochondrial dysfunction and apoptosis in connection with its hepatotoxicity remains unclear. The objective of our study was to find out the link between mitochondrial dynamics and cell death in triptolide induced hepatotoxicity. We treated L02 cells with 25 nM concentration of triptolide. The results demonstrated that triptolide treatment caused an increase in apoptotic cell death, mitochondrial depolarization, ROS overproduction, a decrease in ATP production, and mitochondrial fragmentation which in turn is associated with the activation of Drp1 fission protein. Triptolide treatment led to the translocation of Drp1 from the cytosol into outer mitochondrial membrane where it started mitochondrial fission. This fission event is coupled with the mitochondrial release of cytochrome c into the cytosol and subsequently caspase-3 activation. TEM analysis of rat liver tissues revealed the distortion of mitochondrial morphology in triptolide-treated group. Western blot analysis explained that disruption in mitochondrial morphology was attached with the recruitment of Drp1 to mitochondria, cytochrome c release, and caspase-3 activation. However, Mdivi-1 co-treatment inhibited the activation of Drp1 and caspase-3 and blocked the release of cytochrome c into the cytosol. In short, inhibiting Drp1 protein activation may provide a new potential target for curing Drp1-associated apoptosis in triptolide-induced hepatotoxicity.

Ullah A, Chen G, Hussain A, et al. Int J Nanomedicine. 2021;16:4451–4470. The authors have advised there is an error in the author list on page 4451. The text “Muhammad Usman,6” should read “Muhammad Usman,8”. The authors apologize for this error. Read the original article

Transdermal drug delivery for local or systemic therapy provides a potential anticancer modality with a high patient compliance. However, the drug delivery efficiency across the skin is highly challenging due to the physiological barriers, which limit the desired therapeutic effects. In this study, we prepared liposome-in-hydrogels containing a tumor targeting photosensitizer IR780 (IR780/lipo/gels) for tumor photothermal therapy (PTT). The formulation effectively delivered IR780 to subcutaneous tumor and deep metastatic sites, while the hydrogels were applied on the skin overlying the tumor or on an area of distant normal skin. The photothermal antitumor activity of topically administered IR780/lipo/gels was evaluated following laser irradiation. We observed significant inhibition of the rate of the tumor growth without any toxicity associated with the topical administration of hydrogels. Collectively, the topical administration of IR780/lipo/gels represents a new noninvasive and safe strategy for targeted tumor PTT.

Triptolide being an active ingredient of Chinese herbal plant Tripterygium wilfordii Hook f. has severe hepatotoxicity. Previous studies from our lab reported triptolide-induced mitochondrial toxicity in hepatocytes. However, biomolecular mechanisms involved in triptolide-induced mitochondrial dysfunction are not yet entirely clear. We explored the connection between mitochondrial fragmentation and mitophagy in triptolide-induced hepatotoxicity. Triptolide caused an increase in ROS production, a decrease in mitochondrial depolarization, a diminution of ATP generation, a decline in mitochondrial DNA copy number, mitochondrial fragmentation, and disturbance in mitochondrial dynamics in a concentration-dependent manner in L02 cells. Disturbance in mitochondrial dynamics was due to an increased expression of Drp1 fission protein in vitro and in vivo. L02 cells exhibited an increase in the colocalization of lysosomes with mitochondria and autophagosomes with mitochondria in triptolide treated group as compared to control group which was inhibited by Mdivi-1. Transmission electron micrographs of rat liver tissues treated with triptolide (400 μg/kg) revealed activation of mitophagy which was prevented by Mdivi-1 co-treatment. Taken together, our results showed that mitochondrial fission-associated mitophagy is a novel mechanism involved in triptolide-induced hepatotoxicity. For the alleviation of triptolide-induced hepatotoxicity, mitochondrial fission and mitochondrial autophagy signaling pathway can be targeted as a new therapeutic strategy. Graphical abstract ᅟ.

This report describes the development of polyplexes based on CXCR4-inhibiting poly(ethylenimine) derivative (PEI-C) for pulmonary delivery of siRNA to silence plasminogen activator inhibitor-1 (siPAI-1) as a new combination treatment of pulmonary fibrosis (PF). Safety and delivery efficacy of the PEI-C/siPAI-1 polyplexes was investigated in vitro in primary lung fibroblasts isolated from mice with bleomycin-induced PF. Biodistribution analysis following intratracheal administration of fluorescently labeled polyplexes showed prolonged retention in the lungs. Treatment of mice with bleomycin-induced PF using the PEI-C/siPAI-1 polyplexes resulted in a significant down-regulation of the PAI-1 expression and decreased collagen deposition in the lung. The results of this study provide first evidence of the potential benefits of combined inhibition of CXCR4 and PAI-1 in the pulmonary treatment of PF.

Handling multiple spatial modes using mode-division multiplexing (MDM) on the platform of integrated photonic chip enables unprecedented communication bandwidth scaling for on chip communication. Significant research effort has been done in past decades on MDM system for exploring efficient mode handling devices. In this paper we have proposed a higher order mode pass filter which has the provision of handling four different modes and pass the highest order mode among them. This four mode filter unfolds multiple modes to deal with which can provide a more flexible operation of MDM system.

Iron deficiency anemia (IDA) is one of the foremost health issues among women of reproductive age. The study highlights to assess the level of awareness about the causes, symptoms, prevention and treatment of IDA among women of reproductive age in district Bahawalpur, province Punjab, Pakistan. A randomized study was conducted by using a self-designed standardized questionnaire disseminated to the hostels of female residents and homes in the immediate vicinity of Islamia University Bahawalpur. Females aged 18-45 years without any previous history of medical or gynecological problems were enlisted. A total number of 200 women were surveyed for awareness of iron deficiency anemia. Seventy three percent (73%) of women (n=146) were aware of the term IDA with the highest proportion of women falling in the age bracket 20-35 years. Most (66.9%) of the women were aware of the fact that their diet contains iron and its importance in health. It is concluded that, in reproductive age women the IDA can be prevented and treated through proper guidance and awareness through education.

A series of barriers including poor drug solubility, stability, biocompatibility, bioavailability and pharmacokinetics, distribution to normal tissues, hemorheological flow limitations, multidrug resistance (MDR), and metastasis compromise cancer therapeutic effects. Nanotechnologies provide potential solutions to address these problems by taking advantage of distinct mechanisms of action of multiple therapeutics/modalities. In this regard, hybrid nanomaterials hold great promise for tremendous potential applications. In cancer diagnosis and therapy, a combination of the unique physical and chemical properties of two or more classes of nanomaterials can be used to produce versatile new categories of nanomaterials for gene/drug delivery, immunotherapy, molecular diagnostic, and bio-imaging. Such nanoplatforms of hybrid materials expand the functionality of single-component systems by synergistically killing of target tumor tissues and cells. This review will elaborate on current advances in the design/development, biomedical applications, and therapeutic advantages of state-of-the-art organic-inorganic hybrid nanomaterials used in cancer theranostics. We believe that this class of hybrid nanotechnology might provide new prospects for clinical therapy and management of cancer.

Fluorination is an attractive strategy for the improvement of transfection efficiency of nucleic acid delivery vectors. Bioreducible poly(amido amine)s (bPAAs) are an important class of biomaterials exhibited to effectively deliver multiple nucleic acids. However, still, the effects of fluoroalkyl chain length and density of bPAA on siRNA delivery are unveiled. Here, we synthesized bPAAs and grafted with different chain lengths and densities of fluorocarbon compounds. Furthermore, we prepared a library of complexes of fluorinated bPAA and siRNA, and investigated the effects of fluorination on the siRNA delivery in vitro and in vivo. We found that all the synthesized bPAAs readily formed complexes with siRNA and the fluorinated complexes considerably achieved improved gene silencing efficacies both in vitro and in vivo. Dramatically, the gene silencing efficacy was increased with increasing fluorine contents. Heptafluorobutyric anhydride (HF) modified bPAAs achieved better gene silencing efficacy when compared with bPAAs fluorinated by trifluoroacetic anhydride (TF) and pentafluoropropionic anhydride (PF) providing the evidence for choosing of best one among fluorocarbon compounds. In addition, a combination of fluorination with bioreducibility enables efficient and safe siRNA delivery.

Background: Liver fibrosis is a chronic liver disease associated with an excessive accumulation of extracellualr matrix (ECM) proteins which ultimately lead to cirrohosis and hepatocellular carcinoma. Purpose: Liver fibrosis therapies that use combination approaches with the ability to affect multiple disease pathways have proven higher efficacies. This study aimed at optimizing and characterizing the co-encapsulation of pirfenidone (PF) and AMD3100 (AMD) into CXCR4-targeted combination liposomes (CTC liposome) for CXCR4 targeting, and the inhibition of major molecular culprits ie α-SMA, CXCR4, TGFβ, and P-p38 involved in liver fibrosis in-vitro. Methods: The CTC liposomes were prepared using the thin-film hydration method. The concentration of encapsulated AMD and PF was measured by HPLC and UV spectrophotometry, respectively. Tramsmission electron microscopy (TEM) was used to determine the liposomal morphology. The CXCR4 targeting ability was determined by CXCR4 redistribution assay. Confocal microscopy and flowcytometry were used to determine the CXCR4 mediated cell uptake. The apoptosis inducing and protein downreguating ability of CTC liposomes were determined by apoptosis assay and western blot analysis, respectively. In-vivo biodistribution and Hoechst staining were used to confirm the feasibility of CTC liposome for the in-vivo applications and drug targeted accumulation, respectively. Results: The TEM studies revealed that CTC liposomes were spherical in shape. The cumulative release of AMD and PF from CTC liposome was 67% and 84%, respectively, at 48 h. Compared to the free drug counterparts, encapsulated drugs displayed higher cell viability. The CXCR4 redistribution assay confirmed the CXCR4 targeting and antagonistic ability of CTC liposomes. The CTC liposomes were internalized more effectively via caveolae-mediated endocytic pathways. CTC liposomes displayed aggressive apoptosis (87.3%) in TGFβ-induced activated HSC-T6 cells suggesting a propensity to fibrosis regression. Also, CTC liposomes significantly reduced α-SMA (65%), CXCR4 (77%), TGFβ (89%), and P-p38 (66%) expressions, better than free drugs. CTC@IR780 liposomes (CTC liposomes incorporating IR780 dye) were more accumulated in fibrotic livers compared to free IR780, as judged by in-vivo imaging, biodistribution analysis, and Hoechst staining. These findings suggest that this simple and stable CTC liposomal system holds a great promise for the treatment and prevention of liver fibrosis.

Hydrogels evolved as an outstanding carrier material for local and controlled drug delivery that tend to overcome the shortcomings of old conventional dosage forms for small drugs (NSAIDS) and large peptides and proteins. The aqueous swellable and crosslinked polymeric network structure of hydrogels is composed of various natural, synthetic and semisynthetic biodegradable polymers. Hydrogels have remarkable properties of functionality, reversibility, sterilizability, and biocompatibility. All these dynamic properties of hydrogels have increased the interest in their use as a carrier for peptides and proteins to be released slowly in a sustained manner. Peptide and proteins are remarkable therapeutic agents in today’s world that allow the treatment of severe, chronic and life-threatening diseases, such as diabetes, rheumatoid arthritis, hepatitis. Despite few limitations, hydrogels provide fine tuning of proteins and peptides delivery with enormous impact in clinical medicine. Novels drug delivery systems composed of smart peptides and molecules have the ability to drive self-assembly and form hydrogels at physiological pH. These hydrogels are significantly important for biological and medical fields. The primary objective of this article is to review current issues concerned with the therapeutic peptides and proteins and impact of remarkable properties of hydrogels on these therapeutic agents. Different routes for pharmaceutical peptides and proteins and superiority over other drugs candidates are presented. Recent advances based on various approaches like self-assembly of peptides and small molecules to form novel hydrogels are also discussed. The article will also review the literature concerning the classification of hydrogels on a different basis, polymers used, “release mechanisms” their physical and chemical characteristics and diverse applications.

The indigenous medicinal plant Salvia haematodes Linn (SAL) was screened for its pharmacological activities. The crude extract fractions were prepared in methanol, n-hexane, di chloromethane (DCM) and n-butanol by cold maceration process. The antioxidant effect of the extract fractions was observed by 1-1- diphenyl 2-picryl hydrazine (DPPH) radical scavenging activity. The anti-microbial activity was observed by using disc diffusion method. Furthermore, anti-enzymatic activity was studied against LOX (anti-lipoxygenase), acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The results exhibited that the n-hexane (0.5 mg/mL) and DCM (0.5 mg/mL) fractions of SAL showed 83.3 ± 0.8% and 91.56 ± 0.7 % inhibition of DPPH radical. Whereas, the n-butanol fraction of the crude extract did not show any effect. The methanolic extract (10 mg/disc) of SAL inhibited the growth of E. coli at 12±0.5 mm as compared to ciprofloxacin (17.3 ± 0.5 mm). Moreover, at concentration of 0.5 mg/mL, the n-hexane and DMC extracts of SAL inhibited 68.19±0.39 % and 75.8 ± 1.7% of LOX enzyme respectively, against standard Baicallin (93.7 ± 1.2 % ). The methanol fraction of SAL showed 77.95 ± 0.6 % of AChE inhibition, whereas, Eserine standard inhibited 91.2 ±1.1% of AChE. The methanolic fraction of SAL showed 51.9±0.4 % inhibition of BChE enzyme against standard Eserine (82.8±1.0%). However, the DCM and n-hexane fractions did not elucidate any activity. Therefore, it is concluded that SAL have different pharmacology activities that may be due to presence of certain pharmacologically active compound.

Structural transformation of ezetimibe was performed by fungi Beauvaria bassiana and Cunninghamella blakesleeana. The metabolites were identified by different spectroscopic techniques as (3R,4S)-1-(4-fluorophenyl)-3-((E)-3-(4-fluorophenyl) allyl)-4-(4-hydroxyphenyl) azetidin-2-one (2), (3R, 4S)-1-(4-fluorophenyl)-3-(3-(4fluorophenyl)-3-oxopropyl)-4-(4-hydroxyphenyl) azetidin-2-one (3), (3R,4S) 1-(4-fluorophenyl)-3-(3-(4-fluorophenyl) propyl)-4-(4-hydroxyphenyl) azetidin-2-one (4) and (2R,5S)-N, 5-bis (4-fluorophenyl)-5-hydroxy-2-(4-hydroxybenzyl) pentanamide (5). This study displays two important features of these fungi, viz., their ability to metabolize halogenated compounds, and their capacity to metabolize drugs that are targets of the UDP-Glucuronyl Transferase System, a phenomenon not commonly observed.

Photothermal therapy exerts its anticancer effect by converting laser radiation energy into hyperthermia using a suitable photosensitizer. This study reports development of nanostructured lipid carriers (NLCs) suitable for noninvasive oral delivery of a near-infrared photosensitizer dye IR780. The carrier encapsulating the dye (IR780@NLCs) was stable in simulated gastric and intestinal conditions and showed greatly enhanced oral absorption of IR780 when compared with the free dye. As a result of increased oral bioavailability, enhanced accumulation of the dye in subcutaneous mouse colon tumors (CT-26 cells) was observed following oral gavage of IR780@NLCs. Photothermal antitumor activity of orally administered IR780@NLCs was evaluated following local laser irradiation of the CT-26 tumors. We observed significant effect of the photothermal IR780@NLCs treatment on the rate of the tumor growth and no toxicity associated with the oral administration of IR780@NLCs. Overall, orally administered IR780@NLCs represents a safe and noninvasive method to achieve systemic tumor delivery of a photosensitizing dye for applications in photothermal anticancer therapies.

The present study was carried out to develop oral sustained release tablets of propranolol HCl by different ratios of drug : matrix. Tablets were prepared by direct compression technique using xanthan gum and lactose. All the formulations (tablets) were evaluated for thickness, diameter, hardness, friability, weight variation, content of active ingredient, in vitro dissolution using USP dissolution apparatus-II and swelling index. In case of dissolution, an inverse relationship was noted between amount of xanthan gum and release rate of propranolol HCl and the drug release was gradually enhanced as the amount of the lactose increased. The direct release was observed between swelling index and xanthan gum concentration. Significant difference in different media was observed in release profile, indicating that propranolol HCI has better solubility in HCI buffer pH 1.2. Moreover, dissolution data at differing stirring speeds was also analyzed, indicating that the drug release profile was at 50 rpm comparative to 100 rpm. The kinetic treatment showed the best fitted different mathematical models (zero order, first order, Higuchi's, Hixson-Crowell and Korsmeyer Peppas model. Most of the formulations showed linearity in Higuchi's model. The drug release from these tablets was by Fickian diffusion and anomalous (non-Fickian) mechanisms.

Plants are a major source of food for the world population. Plant diseases contribute to production loss, which can be tackled with continuous monitoring. Manual plant disease monitoring is both laborious and error-prone. Early detection of plant diseases using computer vision and artificial intelligence (AI) can help to reduce the adverse effects of diseases and also helps to overcome the shortcomings of continuous human monitoring. In this study, we have extensively studied the performance of the different state-of-the-art convolutional neural networks (CNNs) classification network architectures i.e. ResNet18, MobileNet, DenseNet201, and InceptionV3 on 18,162 plain tomato leaf images to classify tomato diseases. The comparative performance of the models for the binary classification (healthy and unhealthy leaves), six-class classification (healthy and various groups of diseased leaves), and ten-class classification (healthy and various types of unhealthy leaves) are also reported. InceptionV3 showed superior performance for the binary classification using plain leaf images with an accuracy of 99.2%. DenseNet201 also outperform for six-class classification with an accuracy of 97.99%. Finally, DenseNet201 achieved an accuracy of 98.05% for ten-class classification. It can be concluded that deep architectures performed better at classifying the diseases for the three experiments. The performance of each of the experimental studies reported in this work outperforms the existing literature.