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1.
J Appl Biomater Funct Mater ; 22: 22808000241236020, 2024.
Article in English | MEDLINE | ID: mdl-38462785

ABSTRACT

OBJECTIVE: To investigate the Pinus halepensis extracts and determine its healing and antibacterial effects, and to evaluate the treatment of skin burns. METHODS: Aqueous and ethanolic extracts and topical based on Aleppo pine plant extracts were prepared. Thirty male and female Wistar rats were used to study the cutaneous toxicity of extracts from the bark of P. halepensis. The extracts' healing potential for burn wounds were also assessed by evaluating the clinical and macroscopic aspects of the wounds. The antibacterial activity of crude extracts of P. halepensis as well as its wound healing abilities was verified in this investigation. RESULTS: In animals with acute dermal toxicity, there were no signs of treatment-related toxicity or death. The extracts of these plants could be transformed into phytomedicines for the treatment of infected wounds. The results demonstrated that formulated ointments are successful in treating second-degree burns in rats and may be suitable for the short-term therapeutic treatment of second-degree burns. CONCLUSION: This study successfully answered our problem, regarding the efficacy of our extract for treating second-degree burns in rats. Further studies are needed to confirm these results by identifying the molecules responsible for these activities and examining their mechanism of action.


Subject(s)
Burns , Pinus , Rats , Animals , Rats, Wistar , Wound Healing , Burns/drug therapy , Anti-Bacterial Agents/pharmacology , Skin/injuries
2.
Heliyon ; 10(4): e26657, 2024 Feb 29.
Article in English | MEDLINE | ID: mdl-38420420

ABSTRACT

Amnesia is a major health problem prevalent in almost every part of the world specifically in old age peoples. Vanillin analogues have played an important role in the field medicines. Some of them have been documented to be promising inhibitors of cholinesterases and could therefore, be used as antidepressant, anti-Alzheimer and as neuroprotective drugs. In this connection, the present study was designed to synthesize new vanillin analogues (SB-1 to SB-6) of varied biological potentials. The synthesized compounds were investigated as inhibitors against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes and as scavengers of DPPH and ABTS free radicals followed by behavioural antiamnesic evaluation in mice. The compounds; SB-1, SB-3, SB-4 and SB-6 more potently inhibited AChE with IC50 values of 0.078, 0.157, 0.108, and 0.014 µM respectively. The BChE was more potently inhibited by SB-3 with IC50 of 0.057 µM. Moreover, all of the tested compounds exhibited strong antioxidant potentials with promising results of SB-3 against DPPH with IC50 of 0.305 µM, while SB-5 was most active against ABTS with IC50 of 0.190 µM. The in-vivo studies revealed the improvement in memory deficit caused by scopolamine. Y-Maze and new object recognition test showed a considerable decline in cognitive dysfunctions. In Y-Maze test the spontaneous alteration of 69.44 ± 1% and 84.88 ± 1.35% for SB-1 and 68.92 ± 1% and 80.89 ± 1% for SB-3 at both test doses were recorded while during the novel object recognition test the Discrimination Index percentage of SB-1 was more pronounced as compared to standard drug. All compounds were found to be potent inhibitors of AChE, BChE, DPPH, and ABTS in vitro however, SB-1 and SB-3 were comparatively more potent. SB-1 was also more active in reclamation of memory deficit caused by scopolamine. SB-1 and SB-3 may be considered as excellent drug candidates for treating amnesia subjected to toxicological evaluations in other animal models.

3.
Cancer Biomark ; 38(4): 465-487, 2023.
Article in English | MEDLINE | ID: mdl-38073377

ABSTRACT

AIM: Esophageal Squamous Cell Carcinoma (ESCC) is a histological subtype of esophageal cancer that begins in the squamous cells in the esophagus. In only 19% of the ESCC-diagnosed patients, a five-year survival rate has been seen. This necessitates the identification of high-confidence biomarkers for early diagnosis, prognosis, and potential therapeutic targets for the mitigation of ESCC. METHOD: We performed a meta-analysis of 10 mRNA datasets and identified consistently perturbed genes across the studies. Then, integrated with ESCC ATLAS to segregate 'core' genes to identify consequences of primary gene perturbation events leading to gene-gene interactions and dysregulated molecular signaling pathways. Further, by integrating with toxicogenomics data, inferences were drawn for gene interaction with environmental exposures, trace elements, chemical carcinogens, and drug chemicals. We also deduce the clinical outcomes of candidate genes based on survival analysis using the ESCC related dataset in The Cancer Genome Atlas. RESULT: We identified 237 known and 18 novel perturbed candidate genes. Desmoglein 1 (DSG1) is one such gene that we found significantly downregulated (Fold Change =-1.89, p-value = 8.2e-06) in ESCC across six different datasets. Further, we identified 31 'core' genes (that either harbor genetic variants or are regulated by epigenetic modifications) and found regulating key biological pathways via adjoining genes in gene-gene interaction networks. Functional enrichment analysis showed dysregulated biological processes and pathways including "Extracellular matrix", "Collagen trimmer" and "HPV infection" are significantly overrepresented in our candidate genes. Based on the toxicogenomic inferences from Comparative Toxicogenomics Database we report the key genes that interacted with risk factors such as tobacco smoking, zinc, nitroso benzylmethylamine, and drug chemicals such as cisplatin, Fluorouracil, and Mitomycin in relation to ESCC. We also point to the STC2 gene that shows a high risk for mortality in ESCC patients. CONCLUSION: We identified novel perturbed genes in relation to ESCC and explored their interaction network. DSG1 is one such gene, its association with microbiota and a clinical presentation seen commonly with ESCC hints that it is a good candidate for early diagnostic marker. Besides, in this study we highlight candidate genes and their molecular connections to risk factors, biological pathways, drug chemicals, and the survival probability of ESCC patients.


Subject(s)
Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Humans , Esophageal Squamous Cell Carcinoma/genetics , Esophageal Squamous Cell Carcinoma/pathology , Esophageal Neoplasms/pathology , Desmoglein 1/genetics , Desmoglein 1/metabolism , Down-Regulation , Gene Expression Profiling , Computational Biology , Genomics , Prognosis , RNA, Messenger/genetics , Gene Expression Regulation, Neoplastic , Biomarkers, Tumor/genetics
4.
Heliyon ; 9(11): e21222, 2023 Nov.
Article in English | MEDLINE | ID: mdl-38053906

ABSTRACT

Lavandula stoechas, a Mediterranean plant, renowned in traditional medicine for its health benefits, is also arousing strong interest associated with its essential oils (EOs) with promising therapeutic properties. The aim of this study was to analyze the chemical composition of the plant, as well as to study its major activities, including antioxidant, anti-diabetic, dermatoprotective, anti-inflammatory, and antibacterial effects, focusing on its major molecules. Using the GC-MS method, the main compounds identified in L. stoechas EO (LSEO) were fenchone (31.81 %) and camphor (29.60 %), followed by terpineol (13.14 %) and menthone (8.96 %). To assess their antioxidant activity, three in vitro methods were used (DPPH, FRAP, and ABTS). The results revealed that LSEO exhibited the best antiradical property (54 ± 62 µg/mL) according to the DPPH test, while fenchone demonstrated the highest antioxidant capacity (87 ± 92 µg/mL) in the FRAP test, and camphor displayed the highest antioxidant capacity (96 ± 32 µg/mL) in the ABTS test. However, these results were lower than those obtained by Trolox used as a reference. In addition, study also explored the anti-diabetic potential of LSEO and its major compounds by evaluating their inhibitory activity towards two digestive enzymes, α-glucosidase and α-amylase. Camphor (76.92 ± 2.43 µg/mL) and fenchone (69.03 ± 2.31 µg/mL) exhibited the best inhibitory activities for α-amylase and α-glucosidase assays, respectively. Interestingly, all elements of the study exerted activities superior to those of acarbose, regardless of the test performed. In contrast, the evaluation of the dermatoprotective potential was carried out in vitro by targeting two enzymes involved in cutaneous processes, tyrosinase and elastase. In this light, fenchone (53.14 ± 3.06 µg/mL) and camphor (48.39 ± 1.92 µg/mL) were the most active against tyrosinase and elastase, respectively. It should be noted that the effect of both molecules, as well as that of LSEO, ranged between 53.14 ± 3.06 and 97.45 ± 5.22 µg/mL, which was significantly lower than the standard, quercetin (IC50 of 246.90 ± 2 0.54 µg/mL) against tyrosinase. Furthermore, the anti-inflammatory potential of these elements has been studied by evaluating their ability to inhibit lipooxygenase (LOX), a class of enzymes involved in the inflammatory process in the human body. As a result, the LSEO demonstrated a remarkable effect with an IC50 of 6.34 ± 1.29 µg/mL, which was almost comparable to the standard, quercetin (IC50 = 3.93 ± 0.45 µg/mL). Concerning the antibacterial potential, we carried out a quantitative analysis of the various products tested, revealing a bactericidal activity of the LSEO against the strain L. monocytogenes ATCC 13932 at a minimum effective concentration (MIC = CMB = 0.25). Overall, LSEOs offer significant potential as a source of natural antioxidants, and antidiabetic and anti-inflammatory agents, as well as dermatoprotective and antibacterial compounds. Its major molecules, fenchone and camphor, showed promising activity in these areas of study, making it a valuable candidate for future research and development in the field of natural medicine.

5.
Heliyon ; 9(11): e22546, 2023 Nov.
Article in English | MEDLINE | ID: mdl-38034631

ABSTRACT

Chalcones (designated JA1, JA2 and JA3) were prepared from aromatic aldehyde and acetophenone which were then characterized using various spectroscopic techniques. The antioxidant potential of synthesized compounds was evaluated against DPPH free radical whereas the antidiabetic potential was determined against alpha glucosidase. Further the antidiabetic potential of the synthesized compounds was evaluated in rat model which were given orally experimental animals in doses 10 and 20 mg/kg body weight. The blood biochemical parameters like total cholesterol, triglycerides, alanine phosphatase, serum glutamic pyruvic transaminase, serum glutamic oxaloacetic transaminase, serum creatinine, HDL, and LDL levels were determined using commercially available kits. The antioxidant potential was found high for JA3 followed by JA2 with IC50 value of 64.02 ± 1.47 µg/ml whereas against alpha glucosidase again the same compound with IC50 of 63.04 µg/ml exhibited highest inhibitory potential. The blood glucose level was brought to almost normal level (126.88 and 119.13 mg/dl at 10 and 20 mg/kg body weight) in diabetic rats (induced by STZ) by compound JA3 at the tested doses in comparison to acarbose at day 28th. The blood biochemical parameters were normalized in diabetic rats by compound JA3 compared with diabetic control group. Based on the results JA3 should be considered as effective antioxidant and antidiabetic drug candidate.

6.
Front Biosci (Landmark Ed) ; 28(9): 229, 2023 09 27.
Article in English | MEDLINE | ID: mdl-37796709

ABSTRACT

BACKGROUND: Screening new natural molecules with pharmacological and/or cosmetic properties remains a highly sought-after area of research. Moreover, essential oils and volatile compounds have recently garnered significant interest as natural substance candidates. In this study, the volatile components of Pistacia lentiscus L. essential oils (PLEOs) isolated from the fruit and its main compounds, alpha-pinene, and limonene, are investigated for antioxidant, antidiabetic, and dermatoprotective activities. METHODS: In vitro antioxidant activity was investigated using 2,2'-diphenyl-1-picrylhydrazyl (DPPH), fluorescence recovery after photobleaching (FRAP), and 2,2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) methods. The antidiabetic and dermatoprotective effects were studied using enzyme inhibitory activities. RESULTS: Antioxidant tests showed that PLEO has the best activity (ranging from 29.64 ± 3.04 to 73.80 ± 3.96 µg/mL) compared to its main selected molecules (ranging from 74 ± 3.72 to 107.23 ± 5.03 µg/mL). The α-glucosidase and α-amylase assays demonstrated that the elements tested have a promising antidiabetic potential with IC50values ranging from 78.03 ± 2.31 to 116.03 ± 7.42 µg/mL and 74.39 ± 3.08 to 112.35 ± 4.92 µg/mL for the α-glucosidase and α-amylase assays, respectively, compared to the standard drug. For the tyrosinase test, we found that the EOs (IC50 = 57.72 ± 2.86 µg/mL) followed by limonene (IC50 = 74.24 ± 2.06 µg/mL) and α-pinene (IC50 = 97.45 ± 5.22 µg/mL) all exhibited greater inhibitory effects than quercetin (IC50 = 246.90 ± 2.54 µg/mL). CONCLUSIONS: Our results suggest that the biological activities of PLEO, as well as its main compounds, make them promising candidates for the development of new strategies aimed at improving dermatoprotection and treating diseases associated with diabetes mellitus and oxidative stress.


Subject(s)
Oils, Volatile , Pistacia , Oils, Volatile/pharmacology , Oils, Volatile/chemistry , Limonene/pharmacology , Antioxidants/pharmacology , Antioxidants/chemistry , alpha-Glucosidases , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/chemistry , alpha-Amylases
7.
Heliyon ; 9(9): e19292, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37662785

ABSTRACT

Diabetes mellitus (DM) is the most prevalent endocrine disorder. Numerous individual herbs possess anti-diabetic activity. The seeds of Hordeum vulgare, Elettaria cardamomum and Cicer arietinum are traditionally used to manage DM. The ambition of this work was to formulate the poly-herbal granules (PHGs) comprising of these three functional foods and evaluate their in-vitro antioxidant and antidiabetic potential. The dried seed extracts of Hordeum vulgare, Elettaria cardamomum and Cicer arietinum were used in a ratio of 2.5:1:1 to formulate PHGs by wet granulation method. The ratio of extracts was selected on the basis of traditional phytotherapies popularly used by local Hakeems of Pakistan to achieve glycemic control in diabetic patients resistant to traditional allopathic regime of medicine. The flow properties of developed PHGs were evaluated. The UV-Visible spectroscopic, Fourier Transform Infrared (FTIR) and HPLC-DAD of all seed extracts and PHGs were performed. The in-vitro antioxidant DPPH, FRAP, total antioxidant capacity (TAC) and Nitric Oxide (NO) scavenging assays were carried out on PHGs. The in-vitro antidiabetic activity of PHGs was investigated by alpha-amylase and alpha-glucosidase enzyme inhibition activity. The developed PHGs exhibited excellent flow properties. The UV-Vis spectra of all seed extracts and PHGs demonstrated peak at 278 nm showing the presence of flavonoids and phenols. The FTIR spectra confirmed the existence of flavonoids, and phenols along with amines in seed extracts as well as PHGs. The HPLC-DAD test revealed the existence of gallic acid, ascorbic acid, Quercetin-3-(caffeoyldiglucoside)-7-glucoside, Rosmarinic acid, delphinidin-3,5-diglucosides, Kaempferol-3-feruloylsophoroside-7-glucoside and Phloroglucinol in PHGs. The PHGs exhibited IC50 of 51.23, 58.57, 55.41 and 53.13 µg/mL in DPPH assay, FRAP assay, TAC, Nitric oxide scavenging assays respectively. The PHGs also demonstrated IC50 of 49.97 and 36.16 µg/mL in alpha-amylase and in alpha-glucosidase inhibition assays respectively in dose dependent manner. The developed PHGs exhibited an excellent flow property. These exhibit significant in-vitro antioxidant and antidiabetic profile by virtue of flavonoid and phenolic acid derivatives.

8.
Infect Agent Cancer ; 18(1): 47, 2023 Aug 28.
Article in English | MEDLINE | ID: mdl-37641095

ABSTRACT

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) has a poor prognosis and is one of the deadliest gastrointestinal malignancies. Despite numerous transcriptomics studies to understand its molecular basis, the impact of population-specific differences on this disease remains unexplored. AIMS: This study aimed to investigate the population-specific differences in gene expression patterns among ESCC samples obtained from six distinct global populations, identify differentially expressed genes (DEGs) and their associated pathways, and identify potential biomarkers for ESCC diagnosis and prognosis. In addition, this study deciphers population specific microbial and chemical risk factors in ESCC. METHODS: We compared the gene expression patterns of ESCC samples from six different global populations by analyzing microarray datasets. To identify DEGs, we conducted stringent quality control and employed linear modeling. We cross-compared the resulting DEG lists of each populations along with ESCC ATLAS to identify known and novel DEGs. We performed a survival analysis using The Cancer Genome Atlas Program (TCGA) data to identify potential biomarkers for ESCC diagnosis and prognosis among the novel DEGs. Finally, we performed comparative functional enrichment and toxicogenomic analysis. RESULTS: Here we report 19 genes with distinct expression patterns among populations, indicating population-specific variations in ESCC. Additionally, we discovered 166 novel DEGs, such as ENDOU, SLCO1B3, KCNS3, IFI35, among others. The survival analysis identified three novel genes (CHRM3, CREG2, H2AC6) critical for ESCC survival. Notably, our findings showed that ECM-related gene ontology terms and pathways were significantly enriched among the DEGs in ESCC. We also found population-specific variations in immune response and microbial infection-related pathways which included genes enriched for HPV, Ameobiosis, Leishmaniosis, and Human Cytomegaloviruses. Our toxicogenomic analysis identified tobacco smoking as the primary risk factor and cisplatin as the main drug chemical interacting with the maximum number of DEGs across populations. CONCLUSION: This study provides new insights into population-specific differences in gene expression patterns and their associated pathways in ESCC. Our findings suggest that changes in extracellular matrix (ECM) organization may be crucial to the development and progression of this cancer, and that environmental and genetic factors play important roles in the disease. The novel DEGs identified may serve as potential biomarkers for diagnosis, prognosis and treatment.

9.
Healthcare (Basel) ; 11(13)2023 Jul 03.
Article in English | MEDLINE | ID: mdl-37444753

ABSTRACT

Collaboration between physicians and nurses is essential to healthcare delivery and is associated with high-quality patient care, greater patient satisfaction, and better health outcomes. Hence, it is imperative that doctors and nurses have a particular set of interprofessional collaboration skills. This descriptive cross-sectional study assessed how medical students in the pre-clinical and clinical years perceived attitudes toward collaboration between physicians and nurses in a hospital setting. The Jefferson Scale of Attitude toward Physician-nurse Collaboration (JSAPNC) was reverse-translated into Arabic for the current study. The results showed a total JSAPNC mean score of 46.55, lower than other medical students in other universities. In general, the results of the study showed no significant difference in the total JSAPNC score among medical students when analyzed according to age, clinical exposure, and year level, except in the two factors of JSAPNC: shared education and teamwork (p = 0.038) and caring as opposed to curing (p = 0.043). The findings of this study suggest the necessity of integrating interprofessional education (IPE) across the medical school curriculum because, as future physicians, medical students would be well equipped to treat their patients in partnership with their nursing colleagues.

10.
Biomedicines ; 11(4)2023 Apr 01.
Article in English | MEDLINE | ID: mdl-37189682

ABSTRACT

The technologies for fabrication of nanocrystals have an immense potential to improve solubility of a variety of the poor water-soluble drugs with subsequent enhanced bioavailability. Repaglinide (Rp) is an antihyperglycemic drug having low bioavailability due to its extensive first-pass metabolism. Microfluidics is a cutting-edge technique that provides a new approach for producing nanoparticles (NPs) with controlled properties for a variety of applications. The current study's goal was to engineer repaglinide smart nanoparticles (Rp-Nc) utilizing microfluidic technology (Dolomite Y shape), and then to perform in-vitro, in-vivo, and toxicity evaluations of them. This method effectively generated nanocrystals with average particle sizes of 71.31 ± 11 nm and a polydispersity index (PDI) of 0.072 ± 12. The fabricated Rp's crystallinity was verified by Differential scanning calorimetry (DSC) and Powder X-ray diffraction (PXRD). In comparison to the raw and commercially available tablets, the fabricated Rp's nanoparticles resulted in a higher saturation solubility and dissolving rate (p < 0.05). Rp nanocrystals had a considerably lower (p < 0.05) IC50 value than that of the raw drug and commercial tablets. Moreover, Rp nanocrystals at the 0.5 and 1 mg/kg demonstrated a significant decrease in blood glucose level (mg/dL, p < 0.001, n = 8) compared to its counterparts. Rp nanocrystals at the 0.5 mg/kg demonstrated a significant decrease (p < 0.001, n = 8) in blood glucose compared to its counterparts at a dose of 1 mg/kg. The selected animal model's histological analyses and the effect of Rp nanocrystals on several internal organs were determined to be equivalent to those of the control animal group. The findings of the present study indicated that nanocrystals of Rp with improved anti-diabetic properties and safety profiles can be successfully produced using controlled microfluidic technology, an innovative drug delivery system (DDS) approach.

11.
Microsc Res Tech ; 86(7): 846-861, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37245116

ABSTRACT

The current study aims to utilize the bacteria Paraclostridium benzoelyticum strain 5610 to synthesize bio-genic silver nanoparticles (AgNPs). Biogenic AgNPs were thoroughly examined using various characterization techniques such as UV-spectroscopy, XRD, FTIR, SEM, and EDX. Synthesis of AgNPs was confirmed by UV-vis analysis resulting in absorption peak at 448.31 nm wavelength. The SEM analysis indicated the morphological characteristics and size of AgNPs which was 25.29 nm. The face centered cubic (FCC) crystallographic structure was confirmed by XRD. Furthermore, FTIR study affirmed the capping of AgNPs by different compounds found in biomass of the Paraclostridium benzoelyticum strain 5610. Later, EDX was used to determine the elemental composition with respective concentration and distribution. Additionally, in the current study the antibacterial, anti-inflammatory, antioxidant, anti-aging, and anti-cancer ability of AgNPs was assessed. The antibacterial activity of AgNPs was tested against four distinct sinusitis pathogens: Haemophilus in-fluenza, Streptococcus pyogenes, Moraxella catarrhalis and Streptococcus pneumonia. AgNPs shows significant inhibition zone against Streptococcus pyogenes 16.64 ± 0.35 followed by 14.32 ± 071 for Moraxella catarrhalis. Similarly, the antioxidant potential was found maximum (68.37 ± 0.55%) at 400 µg/mL and decrease (5.48 ± 0.65%) at 25 µg/mL, hence the significant antioxidant ability was observed. Furthermore, anti-inflammatory activity of AgNPs shows the strongest inhibitory action (42.68 ± 0.62%) for 15-LOX with lowest inhibition activity for COX-2 (13.16 ± 0.46%). AgNPs have been shown to exhibit significant inhibitory actions against the enzyme elastases AGEs (66.25 ± 0.49%), which are followed by AGEs of visperlysine (63.27 ± 0.69%). Furthermore, the AgNPs show high toxicity against HepG2 cell line which shows 53.543% reduction in the cell viability after 24 h of treatment. The anti-inflammatory activity demonstrated a potent inhibitory effect of the bio-inspired AgNPs. Overall, the biogenic AgNPs have the ability to be served for the treatments of anti-aging and also due to their anti-cancer, antioxidant abilities NPs may be a useful therapy choice for a variety of disorders including cancer, bacterial infections and other inflammatory diseases. Moreover, further studies are required in the future to evaluate their in vivo biomedical applications. HIGHLIGHTS: Biogenic synthesis of AgNPs using Paraclostridium benzoelyticum Strain for the first time. FTIR analysis confirmed capping of potent biomolecules which are of great use in applied field especially Nanomedicines. Notable antimicrobial activity against sinusitis bacteria and cytotoxic potential of synthesized AgNPs on in vitro basis produce a new idea shifting us to treat cancerous cell lines.


Subject(s)
Metal Nanoparticles , Silver , Silver/pharmacology , Silver/chemistry , Metal Nanoparticles/chemistry , Antioxidants/pharmacology , Bacteria , Plant Extracts/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Glycation End Products, Advanced/pharmacology , Spectroscopy, Fourier Transform Infrared
12.
Int J Mol Sci ; 24(8)2023 Apr 12.
Article in English | MEDLINE | ID: mdl-37108323

ABSTRACT

Small-molecule-inhibitor-based bone differentiation has been recently exploited as a novel approach to regulating osteogenesis-related signaling pathways. In this study, we identified 1-Azakenpaullone, a highly selective inhibitor of glycogen synthase kinase-3ß (GSK-3ß), as a powerful inducer of osteoblastic differentiation and mineralization of human mesenchymal stem cells (MSCs). GSK-3ß is a serine-threonine protein kinase that plays a major role in different disease development. GSK-3ß is a key regulator of Runx2 activity in osteoblastic formation. We evaluated alkaline phosphatase activity and staining assays to assess osteoblast differentiation and Alizarin Red staining to assess the mineralization of cultured human MSCs. Gene expression profiling was assessed using an Agilent microarray platform, and bioinformatics were performed using Ingenuity Pathway Analysis software. Human MSCs treated with 1-Azakenpaullone showed higher ALP activity, increased in vitro mineralized matrix formation, and the upregulation of osteoblast-specific marker gene expression. Global gene expression profiling of 1-Azakenpaullone-treated human MSCs identified 1750 upregulated and 2171 downregulated mRNA transcripts compared to control cells. It also suggested possible changes in various signaling pathways, including Wnt, TGFß, and Hedgehog. Further bioinformatics analysis employing Ingenuity Pathway Analysis recognized significant enrichment in the 1-Azakenpaullone-treated cells of genetic networks involved in CAMP, PI3K (Complex), P38 MAPK, and HIF1A signaling and functional categories associated with connective tissue development. Our results suggest that 1-Azakenpaullone significantly induced the osteoblastic differentiation and mineralization of human MSCs mediated by the activation of Wnt signaling and the nuclear accumulation of ß-catenin, leading to the upregulation of Runx2, a key transcription factor that ultimately promotes the expression of osteoblast-specific genes. Thus, 1-Azakenpaullone could be used as an osteo-promotor factor in bone tissue engineering.


Subject(s)
Mesenchymal Stem Cells , Osteogenesis , Humans , Osteogenesis/genetics , Wnt Signaling Pathway/physiology , Glycogen Synthase Kinase 3 beta/genetics , Glycogen Synthase Kinase 3 beta/metabolism , Cell Differentiation/genetics , beta Catenin/metabolism , Osteoblasts/metabolism , Mesenchymal Stem Cells/metabolism , Core Binding Factor Alpha 1 Subunit/genetics , Core Binding Factor Alpha 1 Subunit/metabolism
13.
Molecules ; 28(5)2023 Feb 27.
Article in English | MEDLINE | ID: mdl-36903459

ABSTRACT

Bacterial resistance to antibiotics and host defense systems is primarily due to bacterial biofilm formation in antibiotic therapy. In the present study, two complexes, bis (biphenyl acetate) bipyridine Cu (II) (1) and bis (biphenyl acetate) bipyridine Zn (II) (2), were tested for their ability to prevent biofilm formation. The minimum inhibitory concentration and minimum bactericidal concentration of complexes 1 and 2 were 46.87 ± 1.822 and 93.75 ± 1.345 and 47.87 ± 1.345 and 94.85 ± 1.466 µg/mL, respectively. The significant activity of both complexes was attributed to the damage caused at the membrane level and was confirmed using an imaging technique. The biofilm inhibitory potential levels of complexes 1 and 2 were 95% and 71%, respectively, while the biofilm eradication potential levels were 95% and 35%, respectively, for both complexes. Both the complexes showed good interactions with the E. coli DNA. Thus, complexes 1 and 2 are good antibiofilm agents that exert their bactericidal actions possibly by disrupting the bacterial membrane and interacting with the bacterial DNA, which can act as a powerful agent to restrain the development of bacterial biofilm on therapeutic implants.


Subject(s)
Anti-Bacterial Agents , Escherichia coli , Anti-Bacterial Agents/pharmacology , Biofilms , Bacteria , Microbial Sensitivity Tests , Zinc
14.
Brain Sci ; 13(3)2023 Mar 21.
Article in English | MEDLINE | ID: mdl-36979333

ABSTRACT

Depression is a serious psychological disorder which negatively affects human feelings and actions. The use of antidepressants is the therapy of choice while treating depression. However, such drugs are associated with severe side effects. There is a need for efficient and harmless drugs. In this connection, the present study was designed to synthesize several substituted benzodiazepine derivatives and explore their antidepressant potentials in an animal model. The chalcone backbone was initially synthesized, which was then converted into several substituted benzodiazepine derivatives designated as 1-6. The synthesized compounds were identified using spectroscopic techniques. The experimental animals (mice) after acclimatation were subjected to forced swim test (FST) and tail suspension test (TST) after oral administration of the synthesized compounds to evaluate their antidepressant potentials. At the completion of the mentioned test, the animals were sacrificed to determine GABA level in their brain hippocampus. The chloro-substituent compound (2) significantly reduced the immobility time (80.81 ± 1.14 s; p < 0.001 at 1.25 mg/kg body weight and 75.68 ± 3.73 s with p < 0.001 at 2.5 mg/kg body weight dose), whereas nitro-substituent compound (5) reduced the immobility time to 118.95 ± 1.31 and 106.69 ± 3.62 s (p < 0.001), respectively, at the tested doses (FST). For control groups, the recorded immobility time recorded was 177.24 ± 1.82 s. The standard drug diazepam significantly reduced immobility time to 70.13 ± 4.12 s while imipramine reduced it to 65.45 ± 2.81 s (p < 0.001). Similarly, in the TST, the compound 2 reduced immobility time to 74.93 ± 1.14 s (p < 0.001) and 70.38 ± 1.43 s (p < 0.001), while compound 5 reduced it to 88.23 ± 1.89 s (p < 0.001) and 91.31 ± 1.73 s (p < 0.001) at the tested doses, respectively, as compared to the control group immobility time (166.13 ± 2.18 s). The compounds 1, 3, 4, and 6 showed weak antidepressant responses as compared to compounds 2 and 5. The compounds 2 and 5 also significantly enhanced the GABA level in the brain's hippocampus of experimental animals, indicating the possible involvement of GABAergic mechanism in alleviating the depression which is evident from the significant increase in mRNA levels for the α subunit of the GABAA receptors in the prefrontal cortex of mice as well. From the results, it can be concluded that compound 2 and 5 could be used as alternative drugs of depression. However, further exploration in this connection is needed in other animal models in order to confirm the observed results in this study.

15.
Cureus ; 15(2): e35180, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36811127

ABSTRACT

INTRODUCTION: Invasive lobular carcinoma (ILC) is the second most common histologic type of breast carcinoma. The etiology of ILC is unknown; however, many contributing risk factors have been suggested. Treatment of ILC can be divided into local and systemic. Our objectives were to assess the clinical presentations, risk factors, radiological findings, pathological types, and surgical options for patients with ILC treated at the national guard hospital. Identify the factors associated with metastasis and recurrence. METHODS: Retrospective cross-sectional descriptive study at a tertiary care center in Riyadh. All adult patients aged 16 years and above, from different nationalities, and both genders, were diagnosed with ILC from 2000 to 2017 and followed up at KAMC. The sampling technique was a non-probability consecutive technique. Among 1066 patients identified, 91 patients were diagnosed with ILC over seventeen years study period. RESULTS: The median age at the primary diagnosis was 50. On the clinical examination, 63 (71%) cases were found to have palpable masses which was the most suspicious finding. On radiology, the most encountered finding was speculated masses which were seen in 76 (84%). Regarding the pathology, unilateral breast cancer was seen in 82 while bilateral breast cancer was found only in eight. For the biopsy, a core needle biopsy was the most commonly used in 83 (91%) patients. The most documented surgery for ILC patients was a modified radical mastectomy. Metastasis in different organs was identified with the musculoskeletal system being the commonest site. Different significant variables were compared between patients with or without metastasis. Skin changes, post-operative invasion, estrogen, progesterone, and HER2 receptors were significantly associated with metastasis. Patients with metastasis were less likely to have conservative surgery. Regarding the Recurrence and five years survival, out of 62 cases, 10 had recurrence within five years, which was more prevalent in patients who had fine needle aspiration, excisional biopsy, and nulliparous patients. CONCLUSION: To our knowledge, this is the first study to exclusively describe ILC in Saudi Arabia. The results of this current study are highly important, as these results provide baseline data of ILC in the capital city of Saudi Arabia.

16.
Plants (Basel) ; 11(23)2022 Nov 24.
Article in English | MEDLINE | ID: mdl-36501262

ABSTRACT

We earlier emphasized in vivo the lavender plant's (Lavandula officinalis Chaix.) anti-inflammatory and estrogenic activities and described the chemical compositions of its hydro-ethanolic (HE) extract. We used LC-MS/MS and GC-MS analyses to profile the phytochemical composition of the HE extract and to assess the analgesic and wound-healing effects of both the hydro-ethanolic (HE) and polyphenolic (LOP) extracts in vivo and in silico. The analgesic activity was studied using two methods: acetic acid and formalin injections in mice. The wound-healing activity was carried out over 25 days using a burn model in rats. In the in silico study, the polyphenols identified in the plant were docked in the active sites of three enzymes: casein kinase-1, cyclooxygenase-2, and glycogen synthase kinase-3ß. The LC-MS/MS identified some phenolic compounds, mainly apigenin, catechin, and myricetin, and the GC-MS analysis revealed the presence of 19 volatile compounds with triazole, D-glucose, hydroxyphenyl, and D-Ribofuranose as the major compounds. The HE and LOP extracts showed significant decreases in abdominal writhes, and the higher licking time of the paw (57.67%) was observed using the LOP extract at 200 mg/kg. Moreover, both extracts showed high healing percentages, i.e., 99.31 and 92.88%, compared to the control groups, respectively. The molecular docking showed that myricetin, amentoflavone, apigenin, and catechin are the most active molecules against the three enzyme receptors. This study sheds light on the potential of L. officinalis Chaix as a source of natural products for pharmaceutical applications for analgesic purposes as well as their utility in promoting burn-healing activity.

17.
Healthcare (Basel) ; 10(11)2022 Nov 07.
Article in English | MEDLINE | ID: mdl-36360568

ABSTRACT

This study investigated people's knowledge of genetics, attitudes toward genetic testing, and views on consanguinity. This cross-sectional study utilized a validated questionnaire modified from published studies to collect data on people's knowledge of genetics and attitudes about genetic testing among 1008 respondents from various Saudi Arabian regions. Using SPSS software version 26, data were analyzed using a t-test, ANOVA, and multivariate analysis. p-values of <0.05 were considered statistically significant. About 59.9% of the participants had sufficient knowledge of genetics, and around 50% had a favorable attitude toward genetic testing. Knowledge of genetics is significantly correlated (p ≤ 0.001) with a positive attitude toward genetic testing. Gender, age, level of education, marital status, family income, and family history were significantly correlated with respondents' understanding of genetics. Gender, family income, residence, and family history were associated with attitudes toward genetic testing at a 0.05 level of significance. There is a need to strengthen peoples' knowledge of genetics and attitudes toward genetic testing through diverse educational programs and healthcare strategies. Impetus on how to disseminate genetic information on consanguinity and transmission of diseases should be prioritized in regions where consanguineous marriages are high.

19.
Front Pharmacol ; 13: 964005, 2022.
Article in English | MEDLINE | ID: mdl-36210807

ABSTRACT

Background: ß-lactams remain the cornerstone of the empirical therapy to treat various bacterial infections. This systematic review aimed to analyze the data describing the dosing regimen of ß-lactams. Methods: Systematic scientific and grey literature was performed in accordance with Preferred Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The studies were retrieved and screened on the basis of pre-defined exclusion and inclusion criteria. The cohort studies, randomized controlled trials (RCT) and case reports that reported the dosing schedule of ß-lactams are included in this study. Results: A total of 52 studies met the inclusion criteria, of which 40 were cohort studies, 2 were case reports and 10 were RCTs. The majority of the studies (34/52) studied the pharmacokinetic (PK) parameters of a drug. A total of 20 studies proposed dosing schedule in pediatrics while 32 studies proposed dosing regimen among adults. Piperacillin (12/52) and Meropenem (11/52) were the most commonly used ß-lactams used in hospitalized patients. As per available evidence, continuous infusion is considered as the most appropriate mode of administration to optimize the safety and efficacy of the treatment and improve the clinical outcomes. Conclusion: Appropriate antibiotic therapy is challenging due to pathophysiological changes among different age groups. The optimization of pharmacokinetic/pharmacodynamic parameters is useful to support alternative dosing regimens such as an increase in dosing interval, continuous infusion, and increased bolus doses.

20.
Neurohospitalist ; 12(4): 617-623, 2022 Oct.
Article in English | MEDLINE | ID: mdl-36147767

ABSTRACT

Background and Purpose: Stroke is an unexpected medical emergency that can result in significant disability. The weekend effect suggests that individuals with acute medical problems are not treated the same way on weekends as they are on weekdays. There is no previous published study about weekend effect on stroke patients from Saudi Arabia. Methods: This was an IRB approved, retrospective, cohort study. All stroke patients admitted between January 2017 and December 2018 were included. Ten standards of care were chosen to assess compliance with standardized care. Seven measures were chosen for acute management of stroke. Results: A total of 731 patients were included, 68.5% were males; 493 (67%) were admitted during weekdays and 238 (33%) on weekends. There was no difference for age (P = .32), gender (P = .32), nationality (P = .62), stroke subtype (P = .27) and stroke severity (P = .69) on weekday or weekend admission. In two-third patients, more than 70% of stroke orders were utilized, with no difference in thrombolysis rate (P = .81). There was no difference in recurrent stroke (P = .86), mortality or discharge disposition (P = .34) between the patients. The patients admitted during weekdays had less complications (38 vs 46%; P = .04). Conclusions: There was no difference in the quality of care provided to stroke patients admitted during weekdays or weekends. There was no difference in the use of acute intervention on weekends and weekdays. Patients had similar outcomes and discharge disposition whether admitted on weekdays or weekends, except that those admitted on weekends had a significantly greater overall number of complications.

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