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1.
Sci Total Environ ; : 174539, 2024 Jul 06.
Article in English | MEDLINE | ID: mdl-38977103

ABSTRACT

Mycotoxins, unavoidable contaminants in feed and feed ingredients, have the potential to influence the incidence and severity of various diseases upon ingestion. Sheep coccidiosis is an enteric disease caused by protozoa of Eimeria spp. However, the extent to which the presence of aflatoxin b1 (AFB1) synergistically exacerbates damage to intestinal health in lambs with Eimeria remains unclear. 50-day-old female lambs were randomly assigned to a 2 × 2 factorial arrangement of treatments for 15 days to assess the impact of AFB1 exposure on lambs with or without Eimeria (E.) ovinoidalis infection. Our findings reveal that AFB1 synergistically intensifies damage to intestinal health in lambs challenged by E. ovinoidalis. This is evidenced by disruptions to the intestinal microbiota and reductions in the production of short-chain fatty acids. AFB1 further aggravates damage to the cecal mechanical barrier. Additionally, AFB1 contributes to the entry of lipopolysaccharide into the bloodstream, activating the inflammatory response. Interestingly, AFB1 exposure history results in an early peak of oocyst excretion and a decreased number of oocyst excretion in E. ovinoidalis infected lambs. This may be closely linked to the destruction of the intestinal epithelial cell structure and its apoptosis, as indicated by a decreased ratio of Bcl-2 to Bax and increased caspase-3 levels. Mechanistically, proteomics analysis identified mitochondrial dysfunction (inhibition of the oxidative phosphorylation pathway) as the primary factor intensifying intestinal epithelial cell destruction caused by coccidia, exacerbated by AFB1 through the inhibiting the conversion of NADH to NAD+ in the cecum of lambs via down-regulation of the PGC-1α/NRF1/TFAM pathway. Overall, these results offer novel insights into the AFB1 complicity in accelerating intestinal damage caused by E. ovinoidalis in lambs. Targeting the mitochondrial oxidative phosphorylation pathway of the intestine may represent a new therapeutic strategy against the detrimental effects of mycotoxin and coccidia.

2.
Biochem Biophys Res Commun ; 729: 150333, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38991397

ABSTRACT

BACKGROUND: Epilepsy is a paroxysmal abnormal hypersynchronous electrical discharge characterized by recurrent seizures. It affects more than 50 million people worldwide. Stress is the leading cause of neurodegeneration and can produce seizures that may lead to or aggravate epilepsy. Inflammation plays a vital role in epilepsy by modulating oxidative stress, and levels of neuroinflammatory cytokines including NF-κB, TNF-α, and IL-1ß. METHODS: Stress-induced changes in behavior were evaluated in mice by employing behavioral assessment tests such as an elevated plus maze, light-dark box, open field test, tail suspension test, Y-maze, novel object recognition test, and Morris water maze in pentylenetetrazole (PTZ) kindled mice. Behavioral changes in all these paradigms including seizure score, latency, and frequency showed an increase in symptoms in PTZ (35 mg/kg) induced seizures in stressed mice (RS-PTZ) as compared to PTZ, Stress, and normal animals. RESULTS: The Enzyme-linked immunosorbent assay (ELISA) results confirmed increased in serum cortisol levels. Histological examinations showed neurodegenerative changes in the hippocampus and cortex regions. The spectrophotometric evaluation showed an increase in oxidative stress by decreasing antioxidant production i.e. reduced glutathione, glutathione -s- transferase, and catalase (CAT), and increasing oxidant levels such as maloaldehyde and nitric oxide. Immunohistochemistry results showed increased expression of NF-κB, TNF-α, and IL-1ß in the cortex and hippocampus of mice brains. CONCLUSIONS: Results from the study conclude that stress increases the likelihood of eliciting an epileptic attack by increasing the level of reactive oxygen species and neuroinflammation.

3.
Sci Rep ; 14(1): 12277, 2024 May 29.
Article in English | MEDLINE | ID: mdl-38806546

ABSTRACT

In recent years, numerous image encryption schemes have been developed that demonstrate different levels of effectiveness in terms of robust security and real-time applications. While a few of them outperform in terms of robust security, others perform well for real-time applications where less processing time is required. Balancing these two aspects poses a challenge, aiming to achieve efficient encryption without compromising security. To address this challenge, the proposed research presents a robust data security approach for encrypting grayscale images, comprising five key phases. The first and second phases of the proposed encryption framework are dedicated to the generation of secret keys and the confusion stage, respectively. While the level-1, level-2, and level-2 diffusions are performed in phases 3, 4, and 5, respectively, The proposed approach begins with secret key generation using chaotic maps for the initial pixel scrambling in the plaintext image, followed by employing the Fibonacci Transformation (FT) for an additional layer of pixel shuffling. To enhance security, Tribonacci Transformation (TT) creates level-1 diffusion in the permuted image. Level-2 diffusion is introduced to further strengthen the diffusion within the plaintext image, which is achieved by decomposing the diffused image into eight-bit planes and implementing XOR operations with corresponding bit planes that are extracted from the key image. After that, the discrete wavelet transform (DWT) is employed to develop secondary keys. The DWT frequency sub-band (high-frequency sub-band) is substituted using the substitution box process. This creates further diffusion (level 3 diffusion) to make it difficult for an attacker to recover the plaintext image from an encrypted image. Several statistical tests, including mean square error analysis, histogram variance analysis, entropy assessment, peak signal-to-noise ratio evaluation, correlation analysis, key space evaluation, and key sensitivity analysis, demonstrate the effectiveness of the proposed work. The proposed encryption framework achieves significant statistical values, with entropy, correlation, energy, and histogram variance values standing at 7.999, 0.0001, 0.0156, and 6458, respectively. These results contribute to its robustness against cyberattacks. Moreover, the processing time of the proposed encryption framework is less than one second, which makes it more suitable for real-world applications. A detailed comparative analysis with the existing methods based on chaos, DWT, Tribonacci transformation (TT), and Fibonacci transformation (FT) reveals that the proposed encryption scheme outperforms the existing ones.

4.
Heliyon ; 10(7): e28290, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38689953

ABSTRACT

In this work there was investigated the synergistic effect of the nanomaterials-the Montmorillonite (MMT) and the vanadium pentoxide (V2O5) on the polyvinyl alcohol (PVA)/starch composite. The composite films were prepared by the solvent casting method. The characterization of the composites showed that the addition of the MMT and the V2O5 to PVA/starch composite decreased the water solubility and water absorption capacity of the film. Both of the reinforcement materials enriched values of thermal conductivity and thermal stability of the composite. The TG/DTA and universal testing machine (UTM) analysis exhibited that MMT and V2O5 augmented the thermal robustness and tensile strength of composites and decreased the strain to break. It was also observed that greater MMT concentration accelerates mechanical strength deterioration of the film owing to agglomeration. The scanning electron microscopy (SEM) analysis reflected great change in the surface morphology of the films in the presence and absence of MMT and V2O5. This was due to the interaction amid constituents of the composite. The chemical interaction between the PVA, Starch, MMT and the V2O5 was also established via Fourier-transform infrared spectroscopy (FTIR) analysis, which revealed fluctuations in the absorbance position and intensity of the PVA/Starch. Antimicrobial activities against seven different cultures of bacteria (both-gram positive and -negative) and one fungus (Candida albicans), exposed that antimicrobial performance of the PVA amplified upon addition of the starch, MMT and V2O5, making these composites prospective candidates for the biodegradable packaging materials.

5.
Front Microbiol ; 15: 1343891, 2024.
Article in English | MEDLINE | ID: mdl-38601942

ABSTRACT

The gut microbiota plays an important role in the disease progression of inflammatory bowel disease. Although probiotics are effective against IBD, not many studies have investigated their effects on gut microbiota composition and immunomodulation in mouse colitis models. Our study aimed at the therapeutic effects of Lacticaseibacillus paracasei BNCC345679 for the first time and explored its impact on gut microbiome dysbiosis, inflammatory cytokines, related miRNAs, VCAM-1, oxidative stress, intestinal integrity, and mucus barrier. We found that oral intervention of L. paracasei BNCC345679 affects recovering beneficial microbial taxa, including lactobacillus spp. and akkermansia spp., followed by improved body weight, DAI score, and inflammatory cytokines. L. paracasei BNCC345679 mitigated oxidative stress and increased the expression of intestinal integrity proteins MUC2 and ZO-1. These results suggested that L. paracasei BNCC345679 has the capacity to reduce DSS-induced colitis and has the potential as a supplement for the mitigation of IBD.

6.
Vet Parasitol Reg Stud Reports ; 49: 100993, 2024 04.
Article in English | MEDLINE | ID: mdl-38462299

ABSTRACT

Tick infestation poses a serious threat to animal health, leading to significant losses in terms of vector-borne disease transmission, reduced live weight, lower quality hides, decreased milk production, and impaired reproduction in tropical and subtropical regions worldwide. This study aimed to determine the prevalence, seasonal variation, distribution pattern, and associated risk factors of Ixodid family tick species in the cattle and sheep population of three different districts in Balochistan, Pakistan. This study employed a convenient sampling method, collecting 4080 adult ticks from 816 cattle and sheep of various breeds, ages, and sexes. Specific morphological keys were used to identify the ticks up to the genus and species level. Among cattle, the highest prevalence was recorded for R. (B) annulatus (27.01%), followed by R. (B) microplus (24.02%), and H. anatolicum (20.54%). H. dromedarii (5.29%) was the least prevalent species observed in cattle. In the sheep population, H. anatolicum (30.34%) showed the highest prevalence, followed by H. marginatium (22.99%), and R. (B) annulatus (20.88%). H. dromedarii (6.96%) was the least prevalent species observed in sheep. The prevalence of R. (B) decoloratus, H. anatolicum and H. dromedarii was found to be significantly associated (P < 0.05) with the breed, age, and sex of both cattle and sheep. However, the presence of R. (B) annulatus, R. (B) microplus and H. marginatium tick species showed no significant association (P > 0.05) with these factors. In addition, the prevalence of ticks was higher in younger, female, and crossbred Friesian cattle compared to adults, males, and other breeds. Conversely, the prevalence of ticks was higher in adult, female and Hernai breed of sheep in the studied area. In conclusion, R. (B) annulatus and H. anatolicum are the dominant tick species infesting the cattle and sheep population in Balochistan. Consequently, this study provides valuable insights for developing practical and effective control measures against ticks and tick-borne diseases in the sheep and cattle population of Balochistan, Pakistan.


Subject(s)
Cattle Diseases , Ixodidae , Sheep Diseases , Ticks , Male , Cattle , Animals , Female , Sheep , Prevalence , Pakistan/epidemiology , Cattle Diseases/epidemiology , Risk Factors , Sheep Diseases/epidemiology
7.
Mol Biol Rep ; 51(1): 191, 2024 Jan 25.
Article in English | MEDLINE | ID: mdl-38270743

ABSTRACT

BACKGROUND: Epilepsy is a common neurological disease but around 30% of patients fail to respond to antiepileptic drug (AED) treatment. Genetic variation of the ATP-binding cassette subfamily B, member 1 (ABCB1) gene, a drug efflux transporter may infer treatment resistance by decreasing gastrointestinal absorption and preventing AED entry into the brain. This study examined the impact of ABCB1 genetic variants on carbamazepine responsiveness. MATERIALS AND METHODS: Genomic DNA was extracted from whole blood of 104 epileptic patients. Genotyping of 3 ABCB1 variants (c.C3435T, c.G2677T/A and c.C1236T) was undertaken using validated TaqMan allelic discrimination assays. Plasma carbamazepine levels were measured at 3 and 6 months following the initial dose using high-performance liquid chromatography (HPLC) alongside clinical outcomes evaluation. RESULTS: Nonresponse to carbamazepine (CBZ) was associated significantly with the ABCB1 variants c.C3435T, c.G2677T/A, c.C1236T and TTT, TTC haplotypes (P < 0.05). There was no significant association between variants and plasma CBZ level (P > 0.05). CONCLUSIONS: Our results showed that variant alleles of the ABCB1 gene and TTT, TTC haplotypes were significantly associated with CBZ resistance without affecting the plasma level of carbamazepine. The findings of this study may help to predict patient's response to treatment ultimately it will improve the personalized and evidence based treatment choice of patients with epilepsy.


Subject(s)
Epilepsy , Humans , Epilepsy/drug therapy , Epilepsy/genetics , Carbamazepine/therapeutic use , Anticonvulsants/therapeutic use , Alleles , Brain , ATP Binding Cassette Transporter, Subfamily B/genetics
8.
Artif Cells Nanomed Biotechnol ; 52(1): 84-103, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38235991

ABSTRACT

Neurological disorders such as neurodegenerative diseases and nervous system tumours affect more than one billion people throughout the globe. The physiological sensitivity of the nervous tissue limits the application of invasive therapies and leads to poor treatment and prognosis. One promising solution that has generated attention is Photodynamic therapy (PDT), which can potentially revolutionise the treatment landscape for neurological disorders. PDT attracted substantial recognition for anticancer efficacy and drug conjugation for targeted drug delivery. This review thoroughly explained the basic principles of PDT, scientific interventions and advances in PDT, and their complicated mechanism in treating brain-related pathologies. Furthermore, the merits and demerits of PDT in the context of neurological disorders offer a well-rounded perspective on its feasibility and challenges. In conclusion, this review encapsulates the significant potential of PDT in transforming the treatment landscape for neurological disorders, emphasising its role as a non-invasive, targeted therapeutic approach with multifaceted applications.


Photodynamic therapy is a promising tool to revolutionise the treatment landscape for neurological disorders.The nexus between photodynamic therapy and biological drug conjugation is best suited for non-invasive neurological disorder treatment.


Subject(s)
Nervous System Diseases , Photochemotherapy , Humans , Photosensitizing Agents/pharmacology , Photosensitizing Agents/therapeutic use , Nanotechnology , Drug Delivery Systems , Nervous System Diseases/drug therapy
9.
Pak J Med Sci ; 40(1Part-I): 247-250, 2024.
Article in English | MEDLINE | ID: mdl-38196481

ABSTRACT

A 34-year-old non hypertensive, non-diabetic and ill looking weak woman came to our emergency department with shortness of breath NYHA III-IV, severe bilateral pedal edema extending up to the thighs and gross ascites. Physical examination revealed 3mm pitting ankle and leg edema and hemodynamically was stable with raised jugular venous pressure. There was a closing and opening mechanical click on Cardiac auscultation. At the lower left sternal border, there was grade 2/6 holodiastolic rumble and a grade 2/6 systolic murmur. She had history of mitral valve replacement and tricuspid valve replacement in 2017 with mechanical valves then she had Redo tricuspid valve replacement with mechanical prosthesis again after four months. No known food or drug allergy and psychosocial issues. Her routine bloods Labs were normal and COVID-19 was negative. On chest X-ray P/A view images and echo showed markedly gross left sided pleural effusion. In Coronary angiogram showed normal coronaries and stuck tricuspid valve (Fig.1). Echocardiography report showed preserved LV systolic function (EF=57%), dilated left atrium and right atrium. Prosthetic mitral valve was seen at mitral position, well seated and well-functioning. The mechanical mitral valve was functioning well with normal disc motion with no thrombus formation. Prosthetic tricuspid valve was seen at tricuspid level with peak gradient of 22mmHg and shown stuck mechanical tricuspid discs stuck throughout the cardiac cycle, in a fully open position (Fig.2A and 2B). Atrial fibrillation was shown on ECG. The diagnosis was made as; pannus formation resulting in mechanical TV thrombosis.

10.
J Biomol Struct Dyn ; : 1-18, 2023 Dec 18.
Article in English | MEDLINE | ID: mdl-38109183

ABSTRACT

Yellow fever is a flavivirus having plus-sensed RNA which encodes a single polyprotein. Host proteases cut this polyprotein into seven nonstructural proteins including a vital NS3 protein. The present study aims to identify the most effective inhibitor against the helicase (NS3) using different advanced ligand and structure-based computational studies. A set of 300 ligands was selected against helicase by chemical structural similarity model, which are similar to S-adenosyl-l-cysteine using infiniSee. This tool screens billions of compounds through a similarity search from in-built chemical spaces (CHEMriya, Galaxi, KnowledgeSpace and REALSpace). The pharmacophore was designed from ligands in the library that showed same features. According to the sequence of ligands, six compounds (29, 87, 99, 116, 148, and 208) were taken for pharmacophore designing against helicase protein. Subsequently, compounds from the library which showed the best pharmacophore shared-features were docked using FlexX functionality of SeeSAR and their optibrium properties were analyzed. Afterward, their ADME was improved by replacing the unfavorable fragments, which resulted in the generation of new compounds. The selected best compounds (301, 302, 303 and 304) were docked using SeeSAR and their pharmacokinetics and toxicological properties were evaluated using SwissADME. The optimal inhibitor for yellow fever helicase was 2-amino-N-(4-(dimethylamino)thiazol-2-yl)-4-methyloxazole-5-carboxamide (302), which exhibits promising potential for drug development.Communicated by Ramaswamy H. Sarma.

11.
Front Chem ; 11: 1268949, 2023.
Article in English | MEDLINE | ID: mdl-38025066

ABSTRACT

Introduction: Natural antioxidants are vital to promote health and treat critical disease conditions in the modern healthcare system. This work adds to the index of natural medicines by exploring the antioxidant potential of Dodonaea viscosa Jacq. (Plant-DV). Material and Methods: The aqueous extract of leaves and flower-containing seeds from plant-DV in freshly prepared phosphate buffer is evaluated for antioxidant potential. In vitro antioxidant potential of the nascent and oxidatively stressed extracts was analyzed through glutathione (GSH) assay, hydrogen peroxide (H2O2) scavenging effect, glutathione-S-transferase (GST) assay, and catalase (CAT) activity. In vivo therapeutic assessment is performed in Wistar Albino rats using vitamin C as a positive control. The livers and kidneys of individual animals are probed for glutathione, glutathione-S-transferase, and catalase activities. Results: flower-containing seeds have GSH contents (59.61 µM) and leaves (32.87 µM) in the fresh aqueous extracts. The hydrogen peroxide scavenging effect of leaves is superior to flower-containing seeds with 17.25% and 14.18% respectively after 30 min incubation. However, oxidatively stressed extracts with Ag(I) and Hg(II) show declining GSH and GST levels. The plant extracts are non-toxic in rats at 5000 mg/Kg body weight. Liver and kidneys homogenate reveal an increase in GSH, GST, and CAT levels after treatment with 150 ± 2 mg/kg and 300 ± 2 mg/kg body weight plant extract compared with normal saline-treated negative and vitamin C treated positive control. Discussion: The crude aqueous extracts of leaves and flower-containing seeds of plant-DV show promising antioxidant potential both in in vitro and in vivo evaluation.

12.
Parasitol Res ; 122(12): 2957-2965, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37779159

ABSTRACT

This study aimed to determine the molecular prevalence and associated risk factors of theileriosis in sheep from Balochistan, Pakistan. For this purpose, a total of 408 blood samples were collected from tick-infested sheep in three different zones of Balochistan (i.e., Quetta, Zhob, and Loralai). All the collected samples were analyzed using conventional microscopy techniques, polymerase chain reaction (PCR), 18S small subunit rRNA gene sequencing, and phylogenetic analysis. The results of the microscopy and PCR confirmed the highest prevalence of Theileria species in district Zhob (14.22% and 15.68%) followed by district Loralai (11.52% and 13.97%) and district Quetta (10.29% and 12.00%), respectively. In addition, the prevalence of T. lestoquardi was higher in female sheep (84.12%), followed by adult sheep (74.71%) and the Hernai breed of sheep (28.23%) in the studied area. Similarly, the prevalence of theileriosis was higher in the summer season (40.59%), followed by the spring, autumn, and winter seasons. However, numerous risk factors such as age, sex, area, season, and breeds of the sheep were not significantly correlated (P > 0.05) with the presence of T. lestoquardi, except tick abundance and feeding pattern of animals (P < 0.05). Furthermore, sequencing and phylogenetic analyses of the isolated T. lestoquardi displayed 99% sequence similarity with isolates from Germany, Egypt, Iraq, India, Iran, and Pakistan. Altogether these results showed that T. lestoquardi is the main species causing ovine theileriosis in Balochistan. As a result, large-scale studies are required to design practical control approaches to reduce the risk of theileriosis infection in Balochistan, Pakistan.


Subject(s)
Sheep Diseases , Theileria , Theileriasis , Ticks , Cattle , Animals , Sheep/genetics , Female , Theileriasis/epidemiology , Pakistan/epidemiology , Phylogeny , Ticks/genetics , RNA, Ribosomal, 18S/genetics , Risk Factors , Sheep Diseases/epidemiology
13.
J Appl Genet ; 64(4): 667-678, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37749479

ABSTRACT

Wheat powdery mildew possesses a significant threat to wheat crops not only on a global scale but also in the northern region of Pakistan. Recognizing the need for effective measures, the exploration and utilization of exotic germplasm take on critical importance. To address this, a series of trials were made to investigate the response of 30 European (EU) lines, in addition to the local checks (Siran, Atta-Habib (AH) and Ghanimat-e-IBGE) against wheat powdery mildew at the Himalayan region of Pakistan. The study involved field testing from 2018 to 2022 across multiple locations, resulting in 38 different environments (location × year). In addition to field evaluations, molecular genotyping was also performed. The disease was absent on the tested lines during 2018, 2019, and 2020 whereas it ranged from 0 to 100% at Chitral location during 2021, where 100% was observed only for one EU wheat line "Matrix." The disease prevailed only at Gilgit location (0-60% for EU wheat line "F236") and at Nagar location (0-10% for EU wheat lines Substance and Nelson) during the disease season of 2022. Most of the EU wheat lines showed very low ACI values, due to an overall low disease pressure. Matrix showed the maximum ACI (1.54) followed by Ritter (1.25) and Bli_autrichion (0.87), whereas the minimum (0.1) was for Substance, JB_Asano, and KWS_Loft followed by Canon (0.19), all exhibiting partial resistance. The molecular marker-based screening revealed that Pm38 was the most prevalent and detected in 100% of wheat lines followed by Pm39 (60%) and Pm8 (30%). Six wheat lines (20%) possessed all three Pm genes (Pm8, Pm38, and Pm39) concurrently. The variability observed in this study can be utilized in future breeding efforts aimed at developing resistant wheat varieties.


Subject(s)
Ascomycota , Triticum , Triticum/genetics , Disease Resistance/genetics , Pakistan , Plant Breeding , Plant Diseases/genetics
14.
Heliyon ; 9(6): e17009, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37484229

ABSTRACT

Background and objectives: The present study was carried out to assess the presence of canine Dirofilaria immitis infection in pet dogs in China. Materials and methods: From October 2018 to November 2019, a total of 216 sera were collected from pet hospitals in Shandong, Jiangsu, Shanghai, Zhejiang, and Fujian regions of Eastern China. The sera were tested by using a commercial canine heartworm antibody ELISA test kit. Results: 70.8% of the pets had significant clinical symptoms resembled to heartworm infection; the overall dirofilariosis positivity found was 12.5% (27/216); Significant positive rates differences were observed between symptomatic and asymptomatic dogs (P < 0.05) (i.e. 15.7% and 4.7% respectively).The prevalence of infection in Shandong Province (15.5%) was the highest among the surveyed areas, but the difference among the geographic regions was not statistically significant (P > 0.05). Furthermore, the prevalence detected in summer (28.2%) was significantly higher than in other seasons (P < 0.05). In addition, no significant difference was observed between male and female sex (P > 0.05). Conclusions: Altogether, these results suggest that an epidemic of dirofilariosis exists in eastern coastal China, as such preventive measures should be taken to control the spread of dirofilariosis to reduce the risk of human and pet infection with heartworm.

15.
Int J Pharm ; 643: 123227, 2023 Aug 25.
Article in English | MEDLINE | ID: mdl-37453671

ABSTRACT

We have synthesized new lipidic prodrugs of diclofenac by grafting aliphatic chains (C10, C12, C16 and C18) to diclofenac through an ester bond. Their molecular formulas were confirmed through HR-MS and the formation of ester bond by FTIR and NMR spectroscopy. Nanoparticles of the different prodrugs were successfully formulated using emulsion evaporation method and DSPE-PEG2000 as the only excipient. All nanoparticles were spherical and had a size between 110 and 150 nm, PdI ≤ 0.2 and negative Zeta potential values from -30 to -50 mV. In addition, they were stable upon storage at 4 °C up to 30-35 days. The encapsulation efficiency of the prodrug was above 90 % independently of the aliphatic chain length grafted. Nanoparticles did not induce any toxicity on LPS-activated THP-1 cells up to a concentration of 100 µg/mL (equivalent diclofenac) whereas diclofenac sodium salt IC50 was around 20 µg/mL. Following incubation of nanoparticles with LPS-activated THP-1 cells, a dose dependent inhibition of TNF-α was observed comparable to standard diclofenac sodium. Based on in vitro studies representative nanoparticles, Prodrug 3 NPs (C16 aliphatic chain) were selected for further in vitro and in vivo studies. Upon incubation in murine plasma, Prodrug 3 NPs underwent an enzymatic cleavage and almost 70 % of diclofenac was released from nanoparticles in 8 h. In vivo studies on a collagen induced arthritis murine model showed contrasted results: on one hand Prodrug 3 NPs led to a significant decrease of arthritis score and of paw volume compared to PBS after the second injection, on the other hand the third injection induced an important hepatic toxicity with the death of half of the mice from the NP group. To promote the reduction of inflammation while avoiding hepatic toxicity using NPs would require to precisely study the No Observable Adverse Effect Level and the schedule of administration in the future.


Subject(s)
Arthritis, Rheumatoid , Nanoparticles , Prodrugs , Mice , Animals , Diclofenac , Prodrugs/chemistry , Lipopolysaccharides , Nanoparticles/chemistry , Esters
16.
Pak J Med Sci ; 39(4): 1091-1094, 2023.
Article in English | MEDLINE | ID: mdl-37492336

ABSTRACT

Objective: To find out the prevalence of diabetes mellitus in patients undergoing coronary artery bypass grafting (CABG). Methods: This retrospective study was conducted in Northwest General Hospital and Research center Hayatabad, Peshawar over a duration of 15 months (December 2020 - March 2022). Every patient was tested through regular laboratory investigations. Diabetes mellitus was established according to WHO standards of fasting plasma glucose >126 mg/dl or two hours postprandial glucose level of 200 mg/dl. Data were analyzed using SPSS. Mean and standard deviation was used for quantitative data. Frequency and percentages were used for qualitative data. Shapiro Wilk's test was done to find the normality of the data. Results: Out of a total of 360 candidates, 129 (36%) individuals were non-diabetic and 231 (64%) candidates were diabetic. Among the diabetic patients, 64 (28%) were female and 167 (72%) were males with a ratio of 1:2.6 respectively. Conclusion: Prevalence of diabetes was 64% among the CABG population. Since the prevalence of diabetes can significantly affect the outcomes of people undergoing CABG, it is essential to generate awareness regarding diabetes among healthcare workers as well as the general population. More extensive research is needed to be carried by various health care centers to figure out the prevalence of diabetes mellitus in cardiac surgery patients.

17.
Environ Sci Pollut Res Int ; 30(41): 93731-93743, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37515622

ABSTRACT

The gastrointestinal microbiota, a complex ecosystem, is involved in the physiological activities of hosts and the development of diseases. Birds occupy a critical ecological niche in the ecosystem, performing a variety of ecological functions and possessing a complex gut microbiota composition. However, the gut microbiota of wild and captive birds has received less attention in the same region. We profiled the fecal gut microbiome of wild wintering whooper swans (Cygnus Cygnus; Cyg group, n = 25), captive black swans (Cygnus Atratus; Atr group, n = 20), and mute swans (Cygnus Olor; Olor group, n = 30) using 16S rRNA gene sequencing to reveal differences in the gut microbial ecology. The results revealed that the three species of swans differed significantly in terms of the alpha and beta diversity of their gut microbiota, as measured by ACE, Chao1, Simpson and Shannon indices, principal coordinates analysis (PCoA) and non-metricmulti-dimensional scaling (NMDS) respectively. Based on the results of the linear discriminant analysis effect size (LEfSe) and random forest analysis, we found that there were substantial differences in the relative abundance of Gottschalkia, Trichococcus, Enterococcus, and Kurthia among the three groups. Furthermore, an advantageous pattern of interactions between microorganisms was shown by the association network analysis. Among these, Gottschalkia had the higher area under curve (AUC), which was 0.939 (CI = 0.879-0.999), indicating that it might be used as a biomarker to distinguish between wild and captive black swans. Additionally, PICRUSt2 predictions indicated significant differences in gut microbiota functions between wild and captive trumpeter swans, with the gut microbiota functions of Cyg group focusing on carbohydrate metabolism, membrane transport, cofactor, and vitamin metabolism pathways, the Atr group on lipid metabolism, and the Olor group on cell motility, amino acid metabolism, and replication and repair pathways. These findings showed that the gut microbiota of wild and captive swans differed, which is beneficial to understand the gut microecology of swans and to improve regional wildlife conservation strategies.


Subject(s)
Anseriformes , Gastrointestinal Microbiome , Animals , Wetlands , Ecosystem , RNA, Ribosomal, 16S , Birds , Ducks , China
19.
J Control Release ; 360: 293-303, 2023 08.
Article in English | MEDLINE | ID: mdl-37391032

ABSTRACT

In an attempt to tune drug release and subsequent pharmacokinetics once administered intravenously, we have synthesized three lipid-drug conjugates (LDCs) of dexamethasone (DXM) each possessing a different lipid-drug chemical linkage: namely ester, carbamate and carbonate. These LDCs were thoroughly characterized before being turned into nanoscale particles by an emulsion-evaporation process using DSPE-PEG2000 (Distearoyl-sn-Glycero-3-Phosphoethanolamine-N-(methoxy(polyethylene glycol)-2000) as the only excipient. Spherical nanoparticles (NPs) of about 140-170 nm, with a negative zeta potential, were obtained for each LDC and exhibited good stability upon storage at 4 °C for 45 days with no recrystallization of LDCs observed. LDC encapsulation efficacy was above 95% for the three LDCs, leading to a LDC loading of about 90% and an equivalent DXM loading above 50%. Although the ester and carbonate NPs did not exhibit any toxicity up to an equivalent DXM concentration of 100 µg/mL, the carbamate LDC NPs appeared very toxic towards RAW 264.7 macrophages and were discarded. Both ester and carbonate LDC NPs were shown to exert anti-inflammatory activity on LPS-activated macrophages. DXM release from LDC NPs in murine plasma was faster from ester than from carbonate NPs. Finally, pharmacokinetics and biodistribution were conducted, showing a lower exposure to DXM from carbonate LDC NPs than from ester LDC NPs, correlated with the slower DXM release from carbonate LDC NPs. These results outline the need for extended studies to find the best prodrug system for extended drug release.


Subject(s)
Nanoparticles , Prodrugs , Mice , Animals , Tissue Distribution , Anti-Inflammatory Agents , Nanoparticles/chemistry , Dexamethasone
20.
Viruses ; 15(4)2023 03 29.
Article in English | MEDLINE | ID: mdl-37112860

ABSTRACT

Lumpy skin disease virus (LSDV) is capable of causing transboundary diseases characterized by fever, nodules on the skin, mucous membranes, and inner organs. The disease may cause emaciation with the enlargement of lymph nodes and sometimes death. It has had endemic importance in various parts of Asia in recent years, causing substantial economic losses to the cattle industry. The current study reported a suspected LSDV infection (based on signs and symptoms) from a mixed farm of yak and cattle in Sichuan Province, China. The clinical samples were found positive for LSDV using qPCR and ELISA, while LSDV DNA was detected in Culex tritaeniorhynchus Giles. The complete genome sequence of China/LSDV/SiC/2021 was determined by Next-generation sequencing. It was found that China/LSDV/SiC/2021 is highly homologous to the novel vaccine-related recombinant LSDV currently emerging in China and countries surrounding China. Phylogenetic tree analysis revealed that the novel vaccine-associated recombinant LSDV formed a unique dendrograms topology between field and vaccine-associated strains. China/LSDV/SiC/2021 was found to be a novel recombinant strain, with at least 18 recombination events via field viruses identified in the genome sequence. These results suggest that recombinant LSDV can cause high mortality in yaks, and its transmission might be due to the Culex tritaeniorhynchus Giles, which acts as a mechanical vector.


Subject(s)
Culex , Lumpy Skin Disease , Lumpy skin disease virus , Animals , Cattle , Lumpy skin disease virus/genetics , Phylogeny , Mosquito Vectors , Disease Outbreaks/veterinary
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