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1.
Drug Dev Ind Pharm ; : 1-40, 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38963406

ABSTRACT

BACKGROUND: Obesity has become a prevalent issue worldwide, leading to various complications such as hyperlipidemia, diabetes, and cardiovascular problems. Statins as FDA approved anti-hyperlipidemic drugs, still poses some concerns upon their administration. Recently, researchers have looked for natural products as an alternative to manage hyperlipidemia and obesity. AIM: This work aimed to study the hypolipidemic effect of Lepidium Sativum Garden Cress (GC) from different preparations; orally administered seeds, and hydrogel, in comparison to atorvastatin. METHODS: GC hydrogel was prepared from the GC aqueous extract and pharmaceutically evaluated for its pH, spreadability, seeds content, homogeneity, rheology, and in vitro release. The rat's body weight, blood glucose levels, total lipid profile, and liver biomarkers were evaluated on obese rats for one month. In addition, the histopathology study was also performed. RESULTS: GC hydrogel had acceptable pharmaceutical properties and showed a sustained release performance over 24 h. Oral and topical GC significantly reduced the lipid profiles, blood sugar and ALT, AST levels more than the negative control group and comparable to atorvastatin. It was found that oral GC showed a significant effect on the percentage decrease in the rat's body weight than the applied hydrogel. Histopathology study revealed a better outcome in the histological structure of pancreas and liver compared with rats feed on high fat diet post treatment for one month. CONCLUSION: GC orally administered, or topically applied hydrogel could be a promising, safe alternative formulation to atorvastatin in managing hyperlipidemia and normalizing body weight of obese rats.

2.
Open Vet J ; 14(5): 1281-1293, 2024 May.
Article in English | MEDLINE | ID: mdl-38938444

ABSTRACT

Background: A fracture is considered a medical emergency leading to considerable complications. Aim: This study aimed to describe the accelerating action of Ag-NPs-FG on fracture healing in rabbits. Methods: Silver NPs (AgNPs) were reduced with fenugreek (FG), loaded into a starch gel base, and investigated for their morphology, size, and charge. Four equal groups were randomly formed of 40 adult male rabbits. A 3.5 mm diameter bone defect was created at the proximal metaphysis of the right tibia in each rabbit. Groups 1-4 were injected with placebo saline, AgNPs-FG, plain gel, and FG-gel at the bone defect zone, respectively. The healing was assessed for 8 weeks postoperatively based on the radiographic, bone turnover markers, and histopathological examinations. Results: The AgNPs-FG was obtained as a faint reddish color, spherical in shape, with an absorbance of 423 nm, a size of 118.0 ± 1.7 nm, and a surface charge of -7.8 ± 0.518 mV. The prepared AgNPs-FG hydrogel was clear, translucent, and homogenous. The pH values were 6.55-6.5 ± 0.2, the viscosity of 4,000 and 1,875 cPs, and spreadability of 1.6 ± 0.14 and 2.0 ± 0.15 for both FG and AgNPs-FG hydrogel, respectively. The radiographic union scale was significantly (p < 0.05) improved in group 2 with a significant (p < 0.05) increase in bone turnover markers was found in comparison to other treated groups. Histopathological examination revealed the formation of mature bone on the 28th postoperative day in groups 2 and 4. Conclusion: Colloidal nano-formulation of AgNPs-FG loaded hydrogel could be a promising formulation to accelerate rabbits' tibial bone healing process.


Subject(s)
Metal Nanoparticles , Silver , Tibia , Trigonella , Animals , Rabbits , Trigonella/chemistry , Silver/administration & dosage , Silver/pharmacology , Silver/chemistry , Male , Metal Nanoparticles/administration & dosage , Metal Nanoparticles/chemistry , Tibia/surgery , Tibia/drug effects , Fracture Healing/drug effects , Plant Extracts/pharmacology , Plant Extracts/administration & dosage , Plant Extracts/chemistry
3.
Vaccine X ; 19: 100500, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38873639

ABSTRACT

Since the first use of vaccine tell the last COVID-19 pandemic caused by spread of SARS-CoV-2 worldwide, the use of advanced biotechnological techniques has accelerated the development of different types and methods for immunization. The last pandemic showed that the nucleic acid-based vaccine, especially mRNA, has an advantage in terms of development time; however, it showed a very critical drawback namely, the higher costs when compared to other strategies, and its inability to protect against new variants. This showed the need of more improvement to reach a better delivery and efficacy. In this review we will describe different vaccine delivery systems including, the most used viral vector, and also variable strategies for delivering of nucleic acid-based vaccines especially lipid-based nanoparticles formulation, polymersomes, electroporation and also the new powerful tools for the delivery of mRNA, which is based on the use of cell-penetrating peptides (CPPs). Additionally, we will also discuss the main challenges associated with each system. Finlay, the efficacy and safety of the vaccines depends not only on the formulations and delivery systems, but also the dosage and route of administration are also important players, therefore we will see the different routes for the vaccine administration including traditionally routes (intramuscular, Transdermal, subcutaneous), oral inhalation or via nasal mucosa, and will describe the advantages and disadvantage of each administration route.

4.
Heliyon ; 10(9): e30440, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38742087

ABSTRACT

Sechium edule, commonly known as chayote is known for its low glycemic index, high fiber content, and rich nutritional profile, which suggests it may be beneficial for individuals with diabetes. While research specifically examining the impact of chayote on diabetes is limited, this study screened its biological impacts by using different biomarkers on streptozotocin-induced diabetic (STZ-ID) rats. The ethanolic extract of the Sechium edule fruits was assessed for different phytochemical, biochemical, and anti-diabetic properties. In the results, chayote extract had high phenolic and flavonoid contents respectively (39.25 ± 0.65 mg/mL and 12.16 ± 0.50 mg/mL). These high phenolic and flavonoid contents showed high implications on STZ-ID rats. Altogether 200 and 400 mg/kg of the extract considerably reduced the blood sugar level and enhanced the lipid profile of the STZ-ID rats. Additionally, they have decreased blood urea and serum creatinine levels. Besides, the levels of SGOT, SGPT, LDH, sodium, and potassium ions were significantly lowered after the administration period. More importantly, the electrocardiogram (ECG) parameters such as QT, RR, and QTc which were prolonged in the diabetic rats were downregulated after 35 days of administration of S. edule extract (400 mg/kg). And, the histological examination of the pancreas and kidney showed marked improvement in structural features of 200 and 400 mg/kg groups when compared to the diabetic control group. Where the increase in the glucose levels was positively correlated with QT, RR, and QTc (r2 = 0.76, r2 = 0.76, and r2 = 0.43) which means that ECG could significantly reflect the diabetes glucose levels. In conclusion, our findings showed that the fruit extract exerts a high potential to reduce artifacts secondary to diabetes which can be strongly suggested for diabetic candidates. However, there is a need to study the molecular mechanisms of the extract in combating artifacts secondary to diabetes in experimental animals.

5.
Colloids Surf B Biointerfaces ; 238: 113930, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38692174

ABSTRACT

Breast cancer is a wide-spread threat to the women's health. The drawbacks of conventional treatments necessitate the development of alternative strategies, where gene therapy has regained hope in achieving an efficient eradication of aggressive tumors. Monocarboxylate transporter 4 (MCT4) plays pivotal roles in the growth and survival of various tumors, which offers a promising target for treatment. In the present study, pH-responsive lipid nanoparticles (LNPs) based on the ionizable lipid,1,2-dioleoyl-3-dimethylammonium propane (DODAP), were designed for the delivery of siRNA targeting MCT4 gene to the breast cancer cells. Following multiple steps of characterization and optimization, the anticancer activities of the LNPs were assessed against an aggressive breast cancer cell line, 4T1, in comparison with a normal cell line, LX-2. The selection of the helper phospholipid to be incorporated into the LNPs had a dramatic impact on their gene delivery performance. The optimized LNPs enabled a powerful MCT4 silencing by ∼90 % at low siRNA concentrations, with a subsequent ∼80 % cytotoxicity to 4T1 cells. Meanwhile, the LNPs demonstrated a 5-fold higher affinity to the breast cancer cells versus the normal cells, in which they had a minimum effect. Moreover, the MCT4 knockdown by the treatment remodeled the cytokine profile in 4T1 cells, as evidenced by 90 % and ∼64 % reduction in the levels of TNF-α and IL-6; respectively. The findings of this study are promising for potential clinical applications. Furthermore, the simple and scalable delivery vector developed herein can serve as a breast cancer-targeting platform for the delivery of other RNA therapeutics.


Subject(s)
Breast Neoplasms , Cytokines , Monocarboxylic Acid Transporters , Muscle Proteins , Nanoparticles , RNA, Small Interfering , Tumor Microenvironment , Breast Neoplasms/pathology , Breast Neoplasms/drug therapy , Breast Neoplasms/metabolism , Breast Neoplasms/genetics , Nanoparticles/chemistry , Humans , Monocarboxylic Acid Transporters/genetics , Monocarboxylic Acid Transporters/metabolism , Monocarboxylic Acid Transporters/antagonists & inhibitors , Female , Cytokines/metabolism , Tumor Microenvironment/drug effects , Muscle Proteins/genetics , Muscle Proteins/metabolism , RNA, Small Interfering/genetics , Cell Line, Tumor , Cell Survival/drug effects , Animals , Mice , Gene Knockdown Techniques , Particle Size , Hydrogen-Ion Concentration
6.
Open Vet J ; 14(1): 534-544, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38633187

ABSTRACT

Background: Equine herpesvirus type 1 (EHV-1) is a major cause of abortion and respiratory disease. Equine herpesvirus type 4 (EHV-4), on the other hand, is exclusively associated with respiratory disease in horse populations worldwide, particularly in Egypt and Arabian countries. Aim: This study aims to investigate the circulation of EHV-1 and EHV-4 in the Arabian horse population through molecular detection and genetic characterization of EHV-1 and/or EHV-4 that may threaten the stability of horse industry. Methods: A total of 80 samples including 50 nasal swabs, 10 vaginal swabs and 20 whole blood samples were collected from vaccinated and registered pure-bred Arabian adult horses from different studs in the governorates of northern Egypt (Cairo, Dakahlyia and Qalyubia) from 2021 to 2022. The collected samples were screened using consensus PCR for detection of EHVs using specific primers targeting DNA polymerase gene. The positive samples were subjected to conventional PCR for detection of EHV-1 and/or EHV-4using specific primers targeting glycoprotein (gB) gene. EHV-1 and EHV-4 amplicons were partially sequenced and phylogenetically analyzed using Sanger method. Results: Consensus PCR revealed that 48 out of 80 samples were positive for EHVs with percentage of 60%. Typing of the selected positive samples using conventional PCR showed that 29 out of 80 were positive for EHV-1 with percentage 36.25%, while 24 out of 80 samples were positive for EHV-4 with percentage 30%. Mixed infections with both viruses were detected in five samples. The amplified products were sequenced using Sanger method and submitted to GenBank under accession number OM362231MG-1 for EHV-1 strain and OM362232 MG-4 for EHV-4 strain. Sequence analysis and alignments of the amplified fragments of the EHV-1 and EHV-4 glycoprotein B (gB) gene to that of GenBank-derived reference strains revealed a high degree of similarity. According to the phylogenetic tree, the obtained sequences of EHV-1 and 4 in the current study showed homogeneity with local Egyptian and foreign EHV-1 and 4 strains and heterogeneity with EHV-2 and 5. Conclusion: The current investigation showed that molecular methods are appropriate assays for an efficient and accurate diagnosis of EHVs. Furthermore, it supports earlier research findings about the prevalence of EHV-1 and 4 in Arabian horse populations in Egypt.


Subject(s)
Herpesviridae Infections , Herpesviridae , Horse Diseases , Pregnancy , Female , Horses , Animals , Egypt , Herpesviridae Infections/veterinary , Phylogeny , Herpesviridae/genetics , Horse Diseases/diagnosis , Glycoproteins
7.
Bone Joint J ; 106-B(2): 158-165, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38425310

ABSTRACT

Aims: Periprosthetic fractures (PPFs) around the knee are challenging injuries. This study aims to describe the characteristics of knee PPFs and the impact of patient demographics, fracture types, and management modalities on in-hospital mortality. Methods: Using a multicentre study design, independent of registry data, we included adult patients sustaining a PPF around a knee arthroplasty between 1 January 2010 and 31 December 2019. Univariate, then multivariable, logistic regression analyses were performed to study the impact of patient, fracture, and treatment on mortality. Results: Out of a total of 1,667 patients in the PPF study database, 420 patients were included. The in-hospital mortality rate was 6.4%. Multivariable analyses suggested that American Society of Anesthesiologists (ASA) grade, history of peripheral vascular disease (PVD), history of rheumatic disease, fracture around a loose implant, and cerebrovascular accident (CVA) during hospital stay were each independently associated with mortality. Each point increase in ASA grade independently correlated with a four-fold greater mortality risk (odds ratio (OR) 4.1 (95% confidence interval (CI) 1.19 to 14.06); p = 0.026). Patients with PVD have a nine-fold increase in mortality risk (OR 9.1 (95% CI 1.25 to 66.47); p = 0.030) and patients with rheumatic disease have a 6.8-fold increase in mortality risk (OR 6.8 (95% CI 1.32 to 34.68); p = 0.022). Patients with a fracture around a loose implant (Unified Classification System (UCS) B2) have a 20-fold increase in mortality, compared to UCS A1 (OR 20.9 (95% CI 1.61 to 271.38); p = 0.020). Mode of management was not a significant predictor of mortality. Patients managed with revision arthroplasty had a significantly longer length of stay (median 16 days; p = 0.029) and higher rates of return to theatre, compared to patients treated nonoperatively or with fixation. Conclusion: The mortality rate in PPFs around the knee is similar to that for native distal femur and neck of femur fragility fractures. Patients with certain modifiable risk factors should be optimized. A national PPF database and standardized management guidelines are currently required to understand these complex injuries and to improve patient outcomes.


Subject(s)
Arthroplasty, Replacement, Knee , Femoral Fractures , Periprosthetic Fractures , Rheumatic Diseases , Adult , Humans , Periprosthetic Fractures/etiology , Knee Joint/surgery , Knee/surgery , Arthroplasty, Replacement, Knee/adverse effects , Femoral Fractures/surgery , Rheumatic Diseases/etiology , Rheumatic Diseases/surgery , Retrospective Studies , Reoperation
8.
AAPS PharmSciTech ; 25(1): 18, 2024 Jan 23.
Article in English | MEDLINE | ID: mdl-38263347

ABSTRACT

Due to tenoxicam (TX)'s poor aqueous solubility (0.072 mg/ml), it is poorly absorbable in the GIT, and the long-term oral administration of TX may cause severe GIT disturbances. Topical administration of TX can help in bypassing the GIT adverse effects. Therefore, in the present work, we constructed different pluronic/lecithin organogels (PLOs) for topical delivery of TX. PLO was constructed simply via direct mixing of an aqueous pluronic solution with lecithin solution. The prepared PLO formulations were characterized for their physicochemical properties including pH, drug content, visual inspection, viscosity, and spreadability. Also, the in vitro release and kinetic studies were carried out to investigate the mechanism of drug release. Moreover, the in vivo studies were carried out by investigating the anti-inflammatory and analgesic activities using albino male rats. The results showed that the modified PLOs have good physicochemical properties. The viscosity of the modified gels is a direct proportionality with both lecithin and pluronic concentrations. Also, subsequently, the drug release rate is directly proportional to gel viscosity. Moreover, the in vivo studies showed that the modified PLOs (F19) showed a significant ( < 0.05%) paw edema inhibition and pain analgesia compared with other investigated groups. Also, the results indicated that the increase in dose is accompanied by higher activity and a longer duration of action which extended to 12 h. Hence, the modified PLOs are promising safe candidates or vehicles for effective TX loading with sustained delivery behavior.


Subject(s)
Lecithins , Piroxicam/analogs & derivatives , Poloxamer , Animals , Rats , Kinetics , Inflammation , Pain
9.
AAPS PharmSciTech ; 25(1): 23, 2024 Jan 24.
Article in English | MEDLINE | ID: mdl-38267656

ABSTRACT

Colorectal cancer (CRC) is a widespread cancer that starts in the digestive tract. It is the third most common cause of cancer deaths around the world. The World Health Organization (WHO) estimates an expected death toll of over 1 million cases annually. The limited therapeutic options as well as the drawbacks of the existing therapies necessitate the development of non-classic treatment approaches. Nanotechnology has led the evolution of valuable drug delivery systems thanks to their ability to control drug release and precisely target a wide variety of cancers. This has also been extended to the treatment of CRC. Herein, we shed light on the pertinent research that has been performed on the potential applications of nanoparticles in the treatment of CRC. The various types of nanoparticles in addition to their properties, applications, targeting approaches, merits, and demerits are discussed. Furthermore, innovative therapies for CRC, including gene therapies and immunotherapies, are also highlighted. Eventually, the research gaps, the clinical potential of such delivery systems, and a future outlook on their development are inspired.


Subject(s)
Colorectal Neoplasms , Nanoparticles , Humans , Immunotherapy , Drug Delivery Systems , Drug Liberation , Colorectal Neoplasms/drug therapy
10.
Drug Dev Ind Pharm ; : 1-15, 2024 Jan 05.
Article in English | MEDLINE | ID: mdl-38180322

ABSTRACT

BACKGROUND: Therapeutic resistance fails cancer treatment. Drug-nanoparticle combinations overcome resistance. Sanguinarine-conjugated nanoparticles may boost sanguinarine's anticancer effects. METHODS: Sanguinarine, HPMC-NPs, and doxorubicin were tested on Adriamycin-resistant MCF-7/ADR breast cancer cells, parent-sensitive MCF-7, and MCR-5 normal cells (DX). RESULTS: Regular distribution, 156 nm diameter, <1 µm average size, 100% intensity-SN is therapeutic. Furthermore, the obtained NPs showed PDI = 0.145, zeta-potential=-37.6, and EE%=90.5%. DX sensitized MCF-7 cells (IC50 = 1.4 µM) more than MCF-7/ADR cells (IC50 = 27 µM) with RR = 19.3. SA and SN were more toxic to MCF-7/ADR cells (overexpressed with P-gp) than their sensitive parent MCF-7 cells (IC50 = 4 µM, RR = 0.6 and 0.6 µM, RR = 0.7). MCR-5 normal lung cells were more resistant to SA (IC50 = 7.2 µM) and SN (IC50 = 1.6 µM) with a selection index > 2. Synergistic cytotoxic interactions reduced the IC50 from 27 µM to 1.6 (CI = 0.1) and 0.9 (CI = 0.4) after DX and nontoxic dosages (IC20) of SA and SN. DS and SN killed 27.1% and 39.4% more cells than DX (7.7%), SA (4.9%), SN (5.5%), or untreated control (0.3%). DS and DSN lowered CCND1 and survival in MCF-7/ADR cells while raising p21 and Casp3 gene and protein expression. CONCLUSIONS: Cellular and molecular studies suggested adjuvant chemosensitizers SA and SN to reverse MDR in breast cancer cells.

11.
Lab Chip ; 24(3): 396-407, 2024 01 30.
Article in English | MEDLINE | ID: mdl-38180130

ABSTRACT

The effects of immunotherapeutics on interactions between immune and cancer cells are modulated by multiple components in the tumour microenvironment (TME), including endothelium and tumour stroma, which provide both a physical barrier and immunosuppressive stimuli. Herein, we report a recirculating chip to enable continuous immune cell recirculation through a microfluidic cell array to include these crucial players. This system consists of a three-layered cell array (µFCA) spatially emulating the TME, with tailored fluidic circuits establishing T cell recirculation. This platform enables the study of dynamics among the TME, immune cells in a circulatory system and cancer cell responses thereof. Through this system, we found that tumour endothelium hindered T cell infiltration into the reconstructed breast cancer tumour compartment. This negative effect was alleviated when treated with anti-human PD-L1 (programmed cell death ligand 1) antibody. Another key stromal component - cancer associated fibroblasts - attenuated T cell infiltration, compared against normal fibroblasts, and led to reduced apoptotic activity in cancer cells. These results confirm the capability of our tumour-on-a-chip system in identifying some key axes to target in overcoming barriers to immunotherapy by recapitulating immune cell interactions with the reconstructed TME. Our results also attest to the feasibility of scaling up this system for high-throughput cancer immunotherapeutic screening.


Subject(s)
Neoplasms , Tumor Microenvironment , Humans , Microfluidics , Immunotherapy , T-Lymphocytes
12.
Drug Dev Ind Pharm ; 50(2): 112-123, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38156891

ABSTRACT

BACKGROUND: Lepidium sativum, Garden Cress (GC), seeds have a lot of natural molecules with a pronounced activity against different disorders. It was reported that GC seeds have the ability to lower the blood glucose level. AIM: The aim of this work was to formulate GC seeds into oral tablets containing a fixed dose of the grounded seeds. Furthermore, the anti-diabetic performance of the prepared tablets was studied in the streptozotocin rats' model in comparison with positive control metformin. METHODS: Micrometrics of GC grounded seeds with different excipients were investigated. Then, GC tablets were prepared via direct compression technique. GC tablets were characterized for their uniformity of dosage unit, friability, hardness, disintegration time, and in vitro release. The antidiabetic effect was studied in rats for a period of 28 days. Glycosylated hemoglobin, liver performance, and lipid levels include total cholesterol (TC), triglycerides (TGs), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) were also estimated. In addition, histopathological study of liver and pancreas was also performed. RESULTS: Prosolv®EasyTab produced tablets with higher hardness, lower disintegration time, and fast release. GC tablets significantly lower the elevated blood glucose level. In addition, they have antihyperlipidemic activity, hepatocellular protective role and restore the histology of the liver and pancreas. CONCLUSION: GC tablets could be a promising alternative formulation to control the high blood glucose level in diabetic rats rather than chemically derivatized drugs.


Subject(s)
Diabetes Mellitus, Experimental , Lepidium , Metformin , Rats , Animals , Hypoglycemic Agents/pharmacology , Blood Glucose , Diabetes Mellitus, Experimental/drug therapy , Tablets/chemistry
13.
Drug Dev Ind Pharm ; 49(12): 723-733, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37906615

ABSTRACT

INTRODUCTION: Bacterial infections caused by different strains of bacteria still one of the most important disorders affecting humans worldwide. Polymers nanocomposite systems could be considered as an alternative to conventional antibiotics to eradicate bacterial infections. SIGNIFICANCE: In an attempt to enhance the antibacterial performance of silver and iron oxide nanoparticles, decrease their aggregation and toxicity, a polymeric hybrid nanocomposite system combining both nanoparticles is produced. METHODS: Magnetic Ag-Fe3O4@polymer hybrid nanocomposites prepared using different polymers, namely polyethylene glycol 4000, ethyl cellulose, and chitosan were synthesized via wet impregnation and ball-milling techniques. The produced nanocomposites were tested for their physical properties and antibacterial activities. RESULTS: XRD, FT-IR, VSM, and TEM results confirmed the successful preparation of hybrid nanocomposites. Hybrid nanocomposites have average crystallite sizes in the following order Ag-Fe3O4@CS (8.9 nm) < Ag-Fe3O4@EC (9.0 nm) < Ag-Fe3O4@PEG4000 (9.4 nm) and active surface area of this trend Ag-Fe3O4@CS (130.4 m2g-1) > Ag-Fe3O4@EC (128.9 m2g-1) > Ag-Fe3O4@PEG4000 (123.4 m2g-1). In addition, they have a saturation magnetization in this order: Ag-Fe3O4@PEG4000 (44.82 emu/g) > Ag-Fe3O4@EC (40.14 emu/g) > Ag-Fe3O4@CS (22.90 emu/g). Hybrid nanocomposites have a pronounced antibacterial action against Bacillus cereus, Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus intermedius compared to iron oxide nanoparticles and positive antibacterial drug. In addition, both Ag-Fe3O4@EC and Ag-Fe3O4@CS have a lower MIC values compared to Ag-Fe3O4@PEG and positive control. CONCLUSION: Magnetic Ag-Fe3O4 hybrid nanocomposites could be promising antibacterial nanomaterials and could pave the way for the development of new materials with even more unique properties and applications.


Subject(s)
Bacterial Infections , Metal Nanoparticles , Nanocomposites , Humans , Polymers , Spectroscopy, Fourier Transform Infrared , Anti-Bacterial Agents/pharmacology , Magnetic Phenomena
14.
Bone Jt Open ; 4(9): 659-667, 2023 09 01.
Article in English | MEDLINE | ID: mdl-37654129

ABSTRACT

Aims: Periprosthetic fractures (PPFs) following hip arthroplasty are complex injuries. This study evaluates patient demographic characteristics, management, outcomes, and risk factors associated with PPF subtypes over a decade. Methods: Using a multicentre collaborative study design, independent of registry data, we identified adults from 29 centres with PPFs around the hip between January 2010 and December 2019. Radiographs were assessed for the Unified Classification System (UCS) grade. Patient and injury characteristics, management, and outcomes were compared between UCS grades. A multinomial logistic regression was performed to estimate relative risk ratios (RRR) of variables on UCS grade. Results: A total of 1,104 patients were included. The majority were female (57.9%; n = 639), ethnically white (88.5%; n = 977), used mobility aids (67%; n = 743), and had a median age of 82 years (interquartile range (IQR) 74 to 87). A total of 77 (7%) had pain prior to the PPF. The most common UCS grade was B2 (33%; n = 368). UCS type D fractures had the longest length of stay (median 19 days (IQR 11 to 26)), highest readmission to hospital (21%; n = 9), and highest rate of discharge to step-down care (52%; n = 23). Multinomial regression suggests that uncemented femoral stems are associated with a reduced risk of UCS C (RRR 0.36 (95% confidence interval (CI) 0.2 to 0.7); p = 0.002) and increased risk of UCS A (RRR 3.3 (95% CI 1.9 to 5.7); p < 0.001), compared to UCS B fracture. Conclusion: The most common PPF type in elderly frail patients is UCS B2. Uncemented stems have a lower risk of UCS C fractures compared to cemented stems. A national PPF database is needed to further identify correlation between implants and fracture subtypes.

15.
Drug Dev Ind Pharm ; 49(9): 572-579, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37688795

ABSTRACT

BACKGROUND: Chemotherapeutic agents have numerous side effects. There is a major interest in using natural and safe plants as food or drink to prevent from cancer. Origanum marjoram (OMAE) is a medicinal plant that can be used as a tea, food, and additive in traditional medicine. OBJECTIVE: This study aimed to evaluate the potential anticancer effects of OMAE as a soft drink for daily use against a model cancer, prevention and treatment. METHOD: MCF-7 cells were chosen as model cancer cells. The MTT assay was used to assess the in vitro inhibitory effects of OMAE on cell growth. Moreover, quantitative real-time PCR (qRT-PCR) was used to detect specific genes associated with cancer, such as ESR1, Bax, Bcl-2, and p53. Furthermore, the DNA damage was evaluated using the comet assay. RESULTS: OMAE has IC50 of 53.1 and IC90 of 97.5 µg/ml dependent inhibition of cell proliferation after 48 h of treatment toward MCF-7. Also, a significant decrease in the expression level of the ESR1 gene in the MCF-7 cell line. Furthermore, there was a significant increase in the comet length and comet-positive cells after treatment with OMAE (88.7%) compared with those in the untreated control cells (9.5%), suggesting a high induction of DNA damage by OMAE. Also, OMAE showed a modification in bcl-2, tumor suppressor gene (p53), and Bax levels and influenced the BAX/BCL-2 ratio via releasing the cytochrome C. CONCLUSION: The results of the study were promising, suggesting that the reduced apoptotic rate of MCF-7 breast cancer cells in this work was correlated to the potential anticancer effect of OMAE which would be a suitable preventable drink against cancer. However, further studies are needed to fully understand the potential of OMAE as a cancer treatment.


Subject(s)
Origanum , Humans , Origanum/metabolism , Apoptosis , bcl-2-Associated X Protein/metabolism , bcl-2-Associated X Protein/pharmacology , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolism , Tumor Suppressor Protein p53/pharmacology , Proto-Oncogene Proteins c-bcl-2/genetics , Proto-Oncogene Proteins c-bcl-2/metabolism , Proto-Oncogene Proteins c-bcl-2/pharmacology , MCF-7 Cells , Cell Proliferation
17.
Colloids Surf B Biointerfaces ; 229: 113466, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37515959

ABSTRACT

Lung cancer is one of the most aggressive and deadliest health threats. There has been an increasing interest in non-coding RNA (ncRNA) recently, especially in the areas of carcinogenesis and tumour progression. However, ncRNA-directed therapies are still encountering obstacles on their way to the clinic. In the present article, we provide an overview on the potential of targeting ncRNA in the treatment of lung cancer. Then, we discuss the delivery challenges and recent approaches enabling the delivery of ncRNA-directed therapies to the lung cancer cells, where we illuminate some advanced technologies including chemically-modified oligonucleotides, nuclear targeting, and three-dimensional in vitro models. Furthermore, advanced non-viral delivery systems recruiting nanoparticles, biomimetic delivery systems, and extracellular vesicles are also highlighted. Lastly, the challenges limiting the clinical trials on the therapeutic targeting of ncRNAs in lung cancer and future directions to tackle them are explored.


Subject(s)
Lung Neoplasms , RNA, Untranslated , Humans , RNA, Untranslated/genetics , RNA, Untranslated/therapeutic use , Lung Neoplasms/therapy , Lung Neoplasms/drug therapy , Carcinogenesis , Molecular Targeted Therapy/methods
18.
Cardiovasc J Afr ; 34: 1-5, 2023 Jun 19.
Article in English | MEDLINE | ID: mdl-37367962

ABSTRACT

AIM: The impact of the COVID-19 pandemic on cardiology fellowship training in sub-Saharan Africa (SSA) is not known. This study aimed to determine the impact of the COVID-19 pandemic on fellowship training, and reviewed the adaptiveness of the existing training systems. METHODS: We conducted a three-month data survey related to the cardiology fellows' clinical exposure at the Aga Khan University Hospital, Kenya, before the COVID-19 pandemic and compared it with a three-month period during the pandemic. Hospital data volumes for patients' contacts, ambulatory and catheterisation laboratory procedures recorded during the periods of March to May 2019 (three-months pre-COVID-19) and March to May 2020 (three-months during the COVID-19 pandemic) were analysed. A comparative fellows' logbook evaluation of recorded cases was also conducted for the two study time periods. In addition, fellows answered a survey questionnaire related to their roles and responsibilities in the hospital, their views on cardiology training during the COVID-19 pandemic and the pandemic's impact on their training. RESULTS: There was a significant reduction in the volume of patients and cardiac procedures during the COVID-19 period compared to the pre-COVID-19 period. In the same line, the number of fellows' training episodes reduced significantly during the COVID-19 pandemic compared to their performances before the pandemic. Fellows felt that the COVID-19 crisis has had a moderate to severe impact on their fellowship training. They however noted an increase in the provision of virtual local and international meetings and conferences, which supported the training positively. CONCLUSION: This study showed that the COVID-19 crisis resulted in a significant reduction in the total volume of patients and cardiac procedures and, in turn, the number of training episodes. This may have limited the fellows from achieving a great amount of skills base in highly technical skills by the end of their training. Opportunities for post-fellowship training in the form of continued mentorship and proctorship would be a valuable option for the trainees if there is a similar pandemic in the future.

19.
Int J Nanomedicine ; 18: 3247-3281, 2023.
Article in English | MEDLINE | ID: mdl-37337575

ABSTRACT

The real problem in pharmaceutical preparation is drugs' poor aqueous solubility, low permeability through biological membranes, and short biological t1/2. Conventional drug delivery systems are not able to overcome these problems. However, cyclodextrins (CDs) and their derivatives can solve these challenges. This article aims to summarize and review the history, properties, and different applications of cyclodextrins, especially the ability of inclusion complex formation. It also refers to the effects of cyclodextrin on drug solubility, bioavailability, and stability. Moreover, it focuses on preparing and applying gold nanoparticles (AuNPs) as novel drug delivery systems. It also studies the uses and effects of cyclodextrins in this field as novel drug carriers and targeting devices. The system formulated from AuNPs linked with CD molecules combines the advantages of both CD and AuNPs. Cyclodextrins benefit in increasing aqueous drug solubility, loading capacity, stability, and size control of gold NPs. Also, AuNPs are applied as diagnostic and therapeutic agents because of their unique chemical properties. Plus, AuNPs possess several advantages such as ease of detection, targeted and selective drug delivery, greater surface area, high loading efficiency, and higher stability than microparticles. In the present article, we tried to present the potential pharmaceutical applications of CD-derived AuNPs in biomedical applications including antibacterial, anticancer, gene-drug delivery, and various targeted drug delivery applications. Also, the article highlighted the role of CDs in the preparation and improvement of catalytic enzymes, the formation of self-assembling molecular print boards, the fabrication of supramolecular functionalized electrodes, and biosensors formation.


Subject(s)
Cyclodextrins , Metal Nanoparticles , Pharmaceutical Preparations , Cyclodextrins/chemistry , Gold , Drug Delivery Systems , Drug Carriers/chemistry
20.
Drug Dev Ind Pharm ; 49(3): 1-12, 2023 Mar.
Article in English | MEDLINE | ID: mdl-37074796

ABSTRACT

BACKGROUND: Ginkgo biloba (GB) leaves extract is known to possess potent antioxidants and other bioactivities such as improved skin conditions and rejuvenation. OBJECTIVE: This study aimed to develop a cosmeceutical preparation to utilize the strong antioxidant potential of GB leaves as part of the skincare formulation. METHODS: Cream incorporated GB (GBC) was prepared by mixing the obtained extract with stearic acid-sodium hydroxide components in an emulsion format. The obtained GBC was characterized for GB contents, uniformity, pH, compatibility, stability, and skin's human application. RESULTS: A homogeneous, physically, and chemically stable, with pH near the skin pH and shiny cream, was obtained. The prepared cream was easy to rub and pearly in appearance. It was effective and safe during the two-week trial conducted on human volunteers according to clinical trial registry protocols. The cream scavenged free radicals in DPPH assay tests. The cream incorporated GB made the skin more spirited and tauter. Furthermore, the wrinkles were reduced and the skin was renewed vigor. CONCLUSION: The GBC worked at the topical level and provided benefits when applied daily for the trial duration. The formulation also provided visually observable anti-wrinkle effects on the skin, with visible improvements in the skin's shape and texture. The prepared cream can be used to rejuvenate the skin.


Subject(s)
Cosmeceuticals , Skin Aging , Humans , Cosmeceuticals/pharmacology , Ginkgo biloba , Rejuvenation , Healthy Volunteers , Skin Cream , Plant Extracts/pharmacology , Antioxidants/pharmacology
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