Antimicrobial resistance and machine learning: past, present, and future.

Machine learning has become ubiquitous across all industries, including the relatively new application of predicting antimicrobial resistance. As the first bibliometric review in this field, we expect it to inspire further research in this area. The review employs standard bibliometric indicators such as article count, citation count, and the Hirsch index (H-index) to evaluate the relevance and impact of the leading countries, organizations, journals, and authors in this field. VOSviewer and Biblioshiny programs are utilized to analyze citation and co-citation networks, collaboration networks, keyword co-occurrence, and trend analysis. The United States has the highest contribution with 254 articles, accounting for over 37.57% of the total corpus, followed by China (103) and the United Kingdom (78). Among 58 publishers, the top four publishers account for 45% of the publications, with Elsevier leading with 15% of the publications, followed by Springer Nature (12%), MDPI, and Frontiers Media SA with 9% each. Frontiers in Microbiology is the most frequent publication source (33 articles), followed by Scientific Reports (29 articles), PLoS One (17 articles), and Antibiotics (16 articles). The study reveals a substantial increase in research and publications on the use of machine learning to predict antibiotic resistance. Recent research has focused on developing advanced machine learning algorithms that can accurately forecast antibiotic resistance, and a range of algorithms are now being used to address this issue.

Silver Nanoparticles from Saudi and Syrian Black Cumin Seed Extracts: Green Synthesis, ADME, Toxicity, Comparative Research, and Biological Appraisal.

Objective: The current study's objective is to highlight the value of using plant resources to identify key bioactive molecules and implement green chemistry in research and development to meet market demand. Materials and Methods: The black cumin seeds (Saudi and Syria originated) were utilized to make silver nanoparticles (Ag-NPs), which were subsequently confirmed using a UV spectrophotometer and color analysis of reaction mixtures. The antibacterial activity of Ag-NPs was tested against E. coli, K. pneumoniae, and S. aureus, and antioxidant activity was measured using the DPPH assay. Swiss-ADME, pkCSM, and ProTox-II were also used to assess the pharmacokinetics, oral bioavailability, toxicity, and safety endpoints of molecules. Result: The antibacterial effect of Ag-NPs from Saudi-origin black cumin seeds was observed higher. In comparison to the standard, the Saudi and Syrian Ag-NPs combined displayed synergistic antibacterial effects and were found to be more susceptible to S. aureus. In comparison to the reference, the antioxidant activity of Ag-NPs indicated 60-85% radical scavenging. All molecules passed the Lipinski rule, the filter (Veber, Egan, and Muegge), PAINS, and the Brenk structural alert (zero violations), and the synthetic score was also found to be in the easy limit (1 to 2). The compounds were found to be non-substrate for p-glycoprotein, high GIA% (>90%), non-inhibitor for CYP3A4, CYP2C19, CYP2C9, CYP2D6 (except 5 and 10), Log Po/w (1.71 to 3.26), TPSA 150 2 and MR 155. The compounds likewise had high Caco2 values (log Papp >0.9) with the exception of 4 and 9 (log Papp 0.9), were non-inhibitors of P-gp-I and II and hERG I and II, and showed no AMES toxicity. Except for molecule 11, no organ damage (hepatotoxicity) or endpoint toxicity (mutagenicity, immunotoxicity, carcinogenicity, and cytotoxicity) was identified in ProTox-II. Conclusion: The current study sheds new light on the significance of bioactive molecules found in black cumin seeds, with molecules 3 and 6 identified as potential leads (highest GIA%, no AMES toxicity, oral rat acute and chronic toxicity, lack of renal OCT2 substrate, high total clearance, and lack of organ toxicity) for further research for a variety of medical applications.

Discovery of Novel Isonipecotic Acid-Based Heteroaryl Amino Acid Derivatives as Potential Anticonvulsant Agents: Design, Synthesis, In-Silico ADME Study, and Molecular Docking Studies.

Background: Epilepsy is a neurological disorder characterized by anomalous brain activity, convulsions, and odd behavior. Several substituted-(naphthalen-2-yl)-3-(1H-indol-3-yl) allyl)-1,4-dihydropyridine-4-carboxylic acid derivatives (5a-j) were intended to be produced in the current research effort to reduce convulsions and seizures. Materials and Methods: The newly developed compounds were produced by the prescribed process. Numerous methods (infrared spectroscopy (IR), nuclear magnetic resonance (NMR), mass, elemental analysis, etc.) were used to characterize these substances. Several models were used to test each of these molecules for anticonvulsant activity. By using the rotarod and ethanol potentiation techniques, neurotoxicity was also evaluated. The study meticulously examined each parameter and showed absorption, distribution, metabolism, and excretion (ADME) predictions for each of the 10 congeners that were produced. In addition, studies on molecular docking employed the gamma amino butyric acid (GABA)-A target protein. Results: Anticonvulsant screening results identified compounds 5f, 5h, 5d, and 5b as the most efficacious of the series. All synthesized equivalents largely passed the neurotoxicity test. The results of molecular docking revealed significant interactions at the active site of GABA-A with LEU B: 99, TYR A: 62, Ala A: 174, and THR B: 202, and the outcomes were good and in agreement with in vivo findings. Conclusions: The study's findings showed that some substances had promising anticonvulsant properties that were comparable to those of the standard drug. The highly active novel anticonvulsant analogs may therefore represent a possible lead, and additional studies may result in a potential new drug candidate.

Quinacrine enhances the efficacy of cisplatin by increasing apoptosis and modulating cancer survival proteins in a colorectal cancer cell line.

BACKGROUND: Cisplatin and platinum-based compounds have been used successfully to treat various cancers. However, their use is often restricted due to the acquired resistance by cancer cells. Over-expression of p53 and inhibition of NF-kB sensitize several cancer cells towards cisplatin-induced apoptosis. Quinacrine, a cytotoxic drug with predictable safety revealed to concurrently suppress NF-kB and activate p53, which may be an attractive adjuvant in cisplatin chemotherapy. Therefore, the objective of the present study was to establish the role of quinacrine as an adjuvant in lowering the dose of cisplatin during cancer therapy to circumvent its toxic effects. MATERIALS AND METHODS: The colon cancer (HCT-8) cells were cultured and cell survival assays were performed using standard procedures. Cell cycle arrest and the extent of apoptosis were determined using a muse cell analyzer. Cancer survival proteins were analyzed using western blotting techniques. RESULTS AND CONCLUSION: We demonstrated that concomitant use of quinacrine with cisplatin increased cell apoptosis, suppressed cell proliferation and inhibited colony formation in a colorectal cancer cell line. Moreover, cell cycle arrest in the G0/G1 and G2/M phases and upregulation of p53 expression were observed. There was also downregulation of NF-kB and Bcl-xL protein expressions, both of which are associated with enhanced cell apoptosis and an increase in the sensitivity of cancer cells to cisplatin, overcoming its chemoresistance. Overall, the results of the present study and available literature clearly indicate that the use of quinacrine as an adjuvant with cisplatin may enhance its anti-cancer activity and reduce chemoresistance.

Farnesol Protects against Cardiotoxicity Caused by Doxorubicin-Induced Stress, Inflammation, and Cell Death: An In Vivo Study in Wistar Rats.

Doxorubicin (DOXO) is an antineoplastic drug that is used extensively in managing multiple cancer types. However, DOXO-induced cardiotoxicity is a limiting factor for its widespread use and considerably affects patients' quality of life. Farnesol (FSN) is a sesquiterpene with antioxidant, anti-inflammatory, and anti-tumor properties. Thus, the current study explored the cardioprotective effect of FSN against DOXO-induced cardiotoxicity. In this study, male Wistar rats were randomly divided into five groups (n = 7) and treated for 14 days. Group I (Control): normal saline, p.o. daily for 14 days; Group II (TOXIC): DOXO 2.4 mg/kg, i.p, thrice weekly for 14 days; Group III: FSN 100 mg/kg, p.o. daily for 14 days + DOXO similar to Group II; Group IV: FSN 200 mg/kg, p.o. daily for 14 days + DOXO similar to Group II; Group V (Standard): nifedipine 10 mg/kg, p.o. daily for 14 days + DOXO similar to Group II. At the end of the study, animals were weighed, blood was collected, and heart-weight was measured. The cardiac tissue was used to estimate biochemical markers and for histopathological studies. The observed results revealed that the FSN-treated group rats showed decrease in heart weight and heart weight/body weight ratio, reversed the oxidative stress, cardiac-specific injury markers, proinflammatory and proapoptotic markers and histopathological aberrations towards normal, and showed cardioprotection. In summary, the FSN reduces cardiac injuries caused by DOXO via its antioxidant, anti-inflammatory, and anti-apoptotic potential. However, more detailed mechanism-based studies are needed to bring this drug into clinical use.

In Vitro and In Vivo Evaluation of a Nano-Tool Appended Oilmix (Clove and Tea Tree Oil) Thermosensitive Gel for Vaginal Candidiasis.

The main objective of the proposed work was the development of a thermosensitive gel (containing clove and tea tree oil) for the management of vaginal candidiasis. Both oils have been recommended to be used separately in a topical formulation for vaginal candidiasis. Incorporating two natural ingredients (clove and tea tree oil) into a product give it a broad antimicrobial spectrum and analgesic properties. The two oils were mixed together at a 3:1 ratio and converted into o/w nanoemulsion using the aqueous titration method and plotting pseudo ternary phase diagrams. Further transformations resulted in a gel with thermosensitive properties. To determine the final formulation's potential for further clinical investigation, in vitro analyses (viscosity measurement, MTT assay, mucoadhesion, ex vivo permeation) and in vivo studies (fungal clearance kinetics in an animal model) were conducted. The current effort leveraged the potential of tea tree and clove oils as formulation ingredients and natural therapeutic agents for vaginal infections. Its synergy generated a stable and effective thermosensitive gel that can be utilized for recurrent candidiasis and other infections.

A current novel perspective approach for coronavirus disease-2019 pandemic outbreak.

Coronavirus disease-2019 is a serious health threat around the globe. Across the world, approximately 142 million people were infected, and three million deaths happened. The fast propagation is also associated with constant anxiety, mental stress, and discomfort in public and health-care professionals. Lack of approved drugs regimen to combat the pandemic challenge concretely is a challenging project for all who are committed to developing remedial assistance. However, the successful development of three vaccines gives a solid roadmap to combat this disease. In this review, we highlighted the current development and challenges of this pandemic.

An updated knowledge of Black seed (Nigella sativa Linn.): Review of phytochemical constituents and pharmacological properties.

N. sativa (N. sativa) has been used since ancient times, when a scientific concept about the use of medicinal plants for the treatment of human illnesses and alleviation of their sufferings was yet to be developed. It has a strong religious significance as it is mentioned in the religious books of Islam and Christianity. In addition to its historical and religious significance, it is also mentioned in ancient medicine. It is widely used in traditional systems of medicine for a number of diseases including asthma, fever, bronchitis, cough, chest congestion, dizziness, paralysis, chronic headache, back pain and inflammation. The importance of this plant led the scientific community to carry out extensive phytochemical and biological investigations on N. sativa. Pharmacological studies on N. sativa have confirmed its antidiabetic, antitussive, anticancer, antioxidant, hepatoprotective, neuro-protective, gastroprotective, immunomodulator, analgesic, antimicrobial, anti-inflammatory, spasmolytic, and bronchodilator activity. The present review is an effort to explore the reported chemical composition and pharmacological activity of this plant. It will help as a reference for scientists, researchers, and other health professionals who are working with this plant and who need up to date knowledge about it.

Type 2 Diabetes, Obesity, and Cancer Share Some Common and Critical Pathways.

Diabetes and cancer are among the most frequent and complex diseases. Epidemiological evidence showed that the patients suffering from diabetes are significantly at higher risk for a number of cancer types. There are a number of evidence that support the hypothesis that these diseases are interlinked, and obesity may aggravate the risk(s) of type 2 diabetes and cancer. Multi-level unwanted alterations such as (epi-)genetic alterations, changes at the transcriptional level, and altered signaling pathways (receptor, cytoplasmic, and nuclear level) are the major source which promotes a number of complex diseases and such heterogeneous level of complexities are considered as the major barrier in the development of therapeutic agents. With so many known challenges, it is critical to understand the relationships and the commonly shared causes between type 2 diabetes and cancer, which is difficult to unravel and understand. Furthermore, the real complexity arises from contended corroborations that specific drug(s) (individually or in combination) during the treatment of type 2 diabetes may increase or decrease the cancer risk or affect cancer prognosis. In this review article, we have presented the recent and most updated evidence from the studies where the origin, biological background, the correlation between them have been presented or proved. Furthermore, we have summarized the methodological challenges and tasks that are frequently encountered. We have also outlined the physiological links between type 2 diabetes and cancers. Finally, we have presented and summarized the outline of the hallmarks for both these diseases, diabetes and cancer.

An Updated Phytopharmacological Review on Medicinal Plant of Arab Region: Apium graveolens Linn.

Apium graveolens Linn. (Karafs) is used in traditional medicine for the treatment of the various ailments. There is a need to explore and authenticate the pharmacological profile and medicinal importance of the Karafs. In this paper, the literature and the published work on Apium were collected using online resources "Google scholar", "Web of science", "Scopus" and "PubMed". Each of the pharmacological activity was searched individually using the keywords "Apium/Karafs/Apium graveolens + individual pharmacological activity". We documented the most cited and most recent literatures. The current findings illuminate the importance Karafs in the traditional medicine and their impact in treating various diseases. This review strongly supports the fact that the Apium has emerged as a good source of medicine in treating various diseases. There is also a need to isolate the bioactive phytochemicals present in this plant.

Antimicrobial activity of aqueous and organic extracts of a Saudi medicinal plant: Rumex nervosus.

OBJECTIVE: The antimicrobial effect of aerial part of Rumex nervosus obtained from the Southern region of Saudi Arabia was evaluated on bacterial strains Staphylococcus aureus, methicillin resistant S. aureus, Enterococcus faecalis, Escherichia coli, Pseudomonas Aeruginosa, and fungal strain Candida albicans. MATERIALS AND METHODS: The solvents used for the extraction were aqueous, hexane, and methanol. The in vitro antimicrobial activity was performed by agar diffusion and disk diffusion methods and the confirmation of this activity was done by the enumeration of colony forming units (CFU). RESULTS: The aqueous extract showed the growth inhibitory effect on Gram-positive bacteria while the Gram-negative P. aeruginosa was the most sensitive microorganism as determined by the agar diffusion technique. Surprisingly, the extract showed little antibacterial activity on other Gram-negative bacteria (E. coli) by this technique. Ethanolic extract was also found to be inhibitory to the growth of microorganisms. Hexane extract was relatively low in antimicrobial activity on Gram-negative E. coli and P. aeruginosa, while both the organic extracts were inhibitory to the growth of the fungus, C. albicans. Hexane gave no conclusive results with agar or disk diffusion methods, but showed the microbial growth inhibition in CFU enumeration. The antibacterial activity of active extracts was compared with vancomycin while antifungal activity of was compared with amphotericin B. CONCLUSION: The results obtained in the present study suggest that R. nervosus showed a marked antimicrobial activity with the test organisms.

Moringa oleifera as an Anti-Cancer Agent against Breast and Colorectal Cancer Cell Lines.

In this study we investigated the anti-cancer effect of Moringa oleifera leaves, bark and seed extracts. When tested against MDA-MB-231 and HCT-8 cancer cell lines, the extracts of leaves and bark showed remarkable anti-cancer properties while surprisingly, seed extracts exhibited hardly any such properties. Cell survival was significantly low in both cells lines when treated with leaves and bark extracts. Furthermore, a striking reduction (about 70-90%) in colony formation as well as cell motility was observed upon treatment with leaves and bark. Additionally, apoptosis assay performed on these treated breast and colorectal cancer lines showed a remarkable increase in the number of apoptotic cells; with a 7 fold increase in MD-MB-231 to an increase of several fold in colorectal cancer cell lines. However, no significant apoptotic cells were detected upon seeds extract treatment. Moreover, the cell cycle distribution showed a G2/M enrichment (about 2-3 fold) indicating that these extracts effectively arrest the cell progression at the G2/M phase. The GC-MS analyses of these extracts revealed numerous known anti-cancer compounds, namely eugenol, isopropyl isothiocynate, D-allose, and hexadeconoic acid ethyl ester, all of which possess long chain hydrocarbons, sugar moiety and an aromatic ring. This suggests that the anti-cancer properties of Moringa oleifera could be attributed to the bioactive compounds present in the extracts from this plant. This is a novel study because no report has yet been cited on the effectiveness of Moringa extracts obtained in the locally grown environment as an anti-cancer agent against breast and colorectal cancers. Our study is the first of its kind to evaluate the anti-malignant properties of Moringa not only in leaves but also in bark. These findings suggest that both the leaf and bark extracts of Moringa collected from the Saudi Arabian region possess anti-cancer activity that can be used to develop new drugs for treatment of breast and colorectal cancers.

Efficacy of Lepidium sativum against carbon tetra chloride induced hepatotoxicity and determination of its bioactive compounds by GCâ¿¿MS.

Lepidium sativum seed (LSS) (family: Cruciferae) has been used in traditional medicine for the treatment of jaundice, liver problems, spleen diseases and gastrointestinal disorders. It was also reported to possess antihypertensive, diuretic, anti-asthmatic, antioxidant, and anti-inflammatory activities. Attempt has been made to study hepatoprotective potential of LSS available in Saudi Arabian Market. The aim of the present study was to determine the hepatoprotective effect of ethanolic extracts of LSS against carbon tetrachloride (CCl4) induced acute liver injury in rats. The bioactive compounds responsible for this activity have been analyzed by GCâ¿¿MS. To evaluate the hepatoprotective activity, six groups (n = 6) of rats were taken. First group was control, second was toxic and other groups received oral test solutions: 100 mg/kg silymarin, or LSS (100, 200, and 400 mg/kg), once daily for 7 consecutive days, followed by hepatotoxicity induction with CCl4. Blood and liver tissues were collected for biochemical, antioxidant and microscopic analyses. The bioactive constituents present in the extract were analyzed by GCâ¿¿MS. Results showed that pretreatment with LSS and silymarin significantly reduced the level of serum alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) and bilirubin (BIL), which was increased significantly in toxic group treated with only CCl4. Histological analysis of liver tissues in groups pretreated with LSS and silymarin showed mild necrosis and inflammation of the hepatocytes compared to the toxic group. GCâ¿¿MS analysis of LSS showed the presence of twelve major fatty acids including alpha-linolenic acid as a major constituent. These results indicated that LSS exerts enhance hepatoprotective activity that could be attributed towards its antioxidant activity, coupled together with the presence of anti-inflammatory compounds in LSS extract.

A review of hepatoprotective plants used in saudi traditional medicine.

Liver disease is one of the major causes of morbidity and mortality across the world. According to WHO estimates, about 500 million people are living with chronic hepatitis infections resulting in the death of over one million people annually. Medicinal plants serve as a vital source of potentially useful new compounds for the development of effective therapy to combat liver problems. Moreover herbal products have the advantage of better affordability and acceptability, better compatibility with the human body, and minimal side effects and is easier to store. In this review attempt has been made to summarize the scientific data published on hepatoprotective plants used in Saudi Arabian traditional medicine. The information includes medicinal uses of the plants, distribution in Saudi Arabia, ethnopharmacological profile, possible mechanism of action, chemical constituents, and toxicity data. Comprehensive scientific studies on safety and efficacy of these plants can revitalise the treatment of liver diseases.