Future Journal of Pharmaceutical Sciences最新文献

{"title":"The role of Shigella spp. in propagating bacillary dysentery in humans and the prominence of nanotechnology in disease prevention","authors":"El Bethel Lalthavel Hmar,&nbsp;Sujata Paul,&nbsp;Hemanta Kumar Sharma","doi":"10.1186/s43094-024-00676-4","DOIUrl":"10.1186/s43094-024-00676-4","url":null,"abstract":"<div><h3>Background</h3><p>Shigellosis, also known as bacillary dysentery, is an acute infection of the intestine. The symptoms can vary from mild watery diarrhoea to severe inflammatory bacillary dysentery, which is characterized by fever, intense abdominal cramps, and the presence of blood and mucus in the stools. While the disease typically resolves on its own, it can become life-threatening in immunocompromised individuals or in the absence of adequate medical care.</p><h3>Main body of the abstract</h3><p><i>Shigella</i> is the primary cause of bacillary dysentery worldwide. It is comprised of four distinct species—<i>S. dysenteriae, S. flexneri</i>, <i>S. boydii,</i> and <i>S. sonnei</i>—each with unique genomic characteristics and disease-causing abilities. <i>Shigella</i> spp. have developed resistance to multiple drugs and have also adapted well to the gut environment over time. They have become well-suited to infecting the human gut epithelial cells and causing dysentery. Consequently, numerous studies have investigated the potential application of nanotechnology in the treatment of shigellosis by leveraging its capability for drug delivery and targeted therapy, thereby improving effectiveness while reducing side effects.</p><h3>Short conclusion</h3><p>It is crucial to maintain ongoing surveillance and develop new strategies to effectively manage this issue. In this review, we shed light on the present comprehension of distinct <i>Shigella</i> spp. and their potential contribution to the pathogenesis of shigellosis, along with their interaction with the gut microbiota. We also provide insight into how nanotechnology may be a major factor in preventing shigellosis in the future.</p></div>","PeriodicalId":577,"journal":{"name":"Future Journal of Pharmaceutical Sciences","volume":"10 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://fjps.springeropen.com/counter/pdf/10.1186/s43094-024-00676-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141942429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Growth inhibition of P. aeruginosa by methanol extract of Bridelia stipularis and identification of active components using in silico studies","authors":"A. Sini,&nbsp;T. K. Bindu,&nbsp;Vinod P. Raphael,&nbsp;K. S. Shaju,&nbsp;Sherry Sebastian","doi":"10.1186/s43094-024-00668-4","DOIUrl":"10.1186/s43094-024-00668-4","url":null,"abstract":"<div><h3>Background</h3><p>Antimicrobial resistance among pathogens is an emerging problem, gaining significant importance recently. Pharmaceutical scientists are constantly exploring innovative and effective antibacterial agents. <i>Pseudomonas aeruginosa</i> (<i>P. aeruginosa</i>) is a bacterium primarily responsible for pneumonia and infections in the liver, kidneys, and other body parts. It is a Gram-negative bacterium that can be controlled by antibiotics such as ciprofloxacin and levofloxacin. However, this pathogen sometimes exhibits resistance to these antibacterial agents.</p><h3>Methods</h3><p>Recognizing the well-known potential of plants as sources of medicinal compounds, our study focused on the ethyl acetate, acetone and methanol extract of the leaves of <i>Bridelia stipularis</i> and its impact on the growth of <i>P. aeruginosa</i> using well diffusion method. To gain insight into the composition of the extract, we conducted GC–MS analysis. After identifying the components present in the extract, we assessed the drug-likeness, absorption, distribution, metabolism, and excretion (ADME) and conducted docking studies of the molecules with the selected structural receptors of <i>P. aeruginosa</i> to find out the active component present in the extract.</p><h3>Results</h3><p>Remarkably, only methanol extract of <i>Bridelia stipularis</i> demonstrated significant antibacterial activity against this pathogen. In silico investigations revealed that two compounds, namely ethyl iso-allocholate and toluene sulfonylhydrazone derivative, exhibited high inhibition potencies. All structural receptors of the pathogen taken for this study were well inhibited by ethyl iso-allocholate while the receptors such as laconizing lipase and penicillin-binding protein of the bacterium were bound well with the 4-phenyl-3-penten-2-one p-toluene sulfonylhydrazone.</p><h3>Conclusions</h3><p>Observations of this study clearly establish that the two phytochemicals present in the methanolic extract, i.e., ethyl iso-allocholate and toluene sulfonylhydrazone derivative of <i>Bridelia stipularis</i> leaves are highly active against the growth of the opportunistic pathogen <i>P. aeruginosa</i>.</p><h3>Graphical abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":577,"journal":{"name":"Future Journal of Pharmaceutical Sciences","volume":"10 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://fjps.springeropen.com/counter/pdf/10.1186/s43094-024-00668-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141863424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Empagliflozin mitigates methotrexate-induced nephrotoxicity in male albino rats: insights on the crosstalk of AMPK/Nrf2 signaling pathway","authors":"Amal Anwar Mishriki,&nbsp;Amira Karam Khalifa,&nbsp;Dina Anwar Ibrahim,&nbsp;Ghada Mohamed Abdel Zaher Hashem,&nbsp;Laila Ahmed Rashed,&nbsp;Sahar Samir Abdelrahman,&nbsp;Hesham M. Mahmoud","doi":"10.1186/s43094-024-00669-3","DOIUrl":"10.1186/s43094-024-00669-3","url":null,"abstract":"<div><h3>Background</h3><p>The anti-diabetic drug, empagliflozin (EMPA), has many pleiotropic actions and is challenged recently to possess renoprotective properties. This renoprotective potential is proposed to be mediated via the activation of AMP-activated protein kinase (AMPK)/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathways. This research investigated the renoprotective potential and the mechanistic pathway of EMPA against methotrexate (MTX)-induced nephrotoxicity and evaluated the role of AMPK by utilizing an AMPK inhibitor, dorsomorphin (Dorso).</p><h3>Methods</h3><p>Thirty male Wistar rats, weighing 180–200 g, were divided equally into five groups. Group I represented the control group. Nephrotoxicity was induced in the remaining rats through the administration of a single intraperitoneal injection of MTX (20 mg/kg). Rats were then randomly assigned to: Group 2 (received MTX injection only); Group 3 (received MTX and EMPA 30 mg/kg/day); Group 4 (received MTX and Dorso 0.2 mg/kg/day), Group 5 (received MTX, Dorso, EMPA). After one week, blood samples were collected, the rats were euthanized, and renal tissues were harvested for biochemical and histomorphometric assessments.</p><h3>Results</h3><p>MTX produced a significant rise in serum creatinine and tissue MDA levels; an increase in BAX, p53, cytochrome-c expression; a reduction in Bcl2 level; and disruption of renal microarchitecture. In contrast, EMPA therapy in group 3, resulted in a significant improvement of all these parameters, correlated with significant increase in AMPK phosphorylation and Nrf2 expression. Importantly, the co-administration of Dorso, in group 5, prevented EMPA’s beneficial effects.</p><h3>Conclusion</h3><p>EMPA has a potential protective effect against MTX-induced toxicity through the activation of the AMPK/Nrf2 signaling pathway.</p></div>","PeriodicalId":577,"journal":{"name":"Future Journal of Pharmaceutical Sciences","volume":"10 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://fjps.springeropen.com/counter/pdf/10.1186/s43094-024-00669-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141863535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analytical method development and validation for simultaneous estimation of seven markers in polyherbal formulation JKC by using RP-HPLC","authors":"Lakshminarayana Misro,&nbsp;Thirupataiah Boini,&nbsp;Rahul Maurya,&nbsp;Thulasi Radhakrishnan,&nbsp;K. S. Rohith,&nbsp;Vijay Kumar,&nbsp;Preeti Sharma,&nbsp;Arjun Singh,&nbsp;Ravindra Singh,&nbsp;Naryanam Srikanth,&nbsp;Rabinarayan Acharya","doi":"10.1186/s43094-024-00670-w","DOIUrl":"10.1186/s43094-024-00670-w","url":null,"abstract":"<div><h3>Background</h3><p>The RP-HPLC method has been established to simultaneous estimation of seven markers in polyherbal formulation JKC using the C₁₈ (25 × 0.46 cm, i.d,5 µm) column. The mobile phase consisted of methanol: water (80:20) at a flow rate of 1.0 mL/min and observed retention time at 2 to 11 min with sharp points. The marker compounds viz. Andrographolide (AG), Piperine (PP), Picroside-I (P-I), Picroside-II (P-II), α-Cyprone (AC), 6-Shogaol (6S), and 6-Gingerol (6G) were quantified in JKC formulations by HPLC method. Detection was performed at the wavelength (λ) of 229 nm for AG, 343 nm for PP, 279 nm for P-I, 264 nm for P-II, 254 nm for AC, and 280 nm for both 6S and 6G by HPLC–PDA detector.</p><h3>Results</h3><p>The marker compounds in JKC formulations were observed in different retention times (R_t) i.e. AG at 3.060 ± 0.01 min, PP at 5.460 ± 0.03 min, P-I at 2.789 ± 0.02 min, P-II at 2.553 ± 0.03 min, AC at 10.951 ± 0.02 min, 6S at 6.302 ± 0.03 min, and 6G at 4.111 ± 0.02 min respectively. The proposed method was validated with acceptable linearity (r² 0.9995–0.9999), precision, robustness, ruggedness, and accuracy (RSD &lt; 2%) under optimum conditions. The limit of detection and quantification of bioactive markers were as: AG (1.386; 4.200 ppm), PP (2.033; 6.161 ppm), P-I (2.822; 8.553 ppm), P-II (2.538; 7.691 ppm), AC (0.269; 0.815 ppm), 6G (0.158; 0.480 ppm), 6S (0.188; 0.569 ppm). The amount (mg/g) of bioactive markers detected and estimated in plants and formulation were as: AG (41.282 ± 0.48; 10.06 ± 0.18), PP (53.81 ± 0.25, 13.82 ± 0.37 in PN, PL; 4.27 ± 0.07), P-I (15.97 ± 0.01; 0.48 ± 0.003), P-II (63.24 ± 0.35; 2.31 ± 0.006), AC (0.42 ± 0.01; 0.36 ± 0.006), 6G (0.71 ± 0.03; 0.16 ± 0.001), and 6S (2.64 ± 0.09; 0.12 ± 0.004) respectively. Method was found to be rugged and robust. The results found for all the validation parameters were within the limits according to ICH guidelines.</p><h3>Conclusion</h3><p>The proposed method is fast, precise, economic, and specific and used for the simultaneously quantifiable analysis of seven major bioactive markers in the ingredients (herbs) and the JKC formulations.</p></div>","PeriodicalId":577,"journal":{"name":"Future Journal of Pharmaceutical Sciences","volume":"10 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://fjps.springeropen.com/counter/pdf/10.1186/s43094-024-00670-w","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141863426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Omega-3 fatty acids: a comprehensive scientific review of their sources, functions and health benefits","authors":"Pradnya G. Patted,&nbsp;Rajashree S. Masareddy,&nbsp;Archana S. Patil,&nbsp;Ravikiran R. Kanabargi,&nbsp;Chetan T. Bhat","doi":"10.1186/s43094-024-00667-5","DOIUrl":"10.1186/s43094-024-00667-5","url":null,"abstract":"<div><h3>Background</h3><p>In recent years, public awareness of healthy diets has significantly increased, leading to a rise in the consumption of nutritional supplements. Among these, omega-3 fatty acids have become particularly popular. <i>n</i> − 3 polyunsaturated fatty acids (PUFAs) are widely distributed in marine and terrestrial environments. The primary sources of marine <i>n</i> − 3 fatty acid supplements are oily fish, such as anchovies, sardines and mackerel. Recently, they have drawn considerable attention for their potential therapeutic benefits in treating a range of illnesses, including cancer, neurological disorders, cardiovascular diseases, immunological and reproductive diseases, respectively.</p><h3>Main text</h3><p>This study explores the many activities of <i>n − </i>3 PUFAs, highlighting their importance in cellular processes that include signaling pathways, cell membrane integrity and structural maintenance. These fatty acids significantly regulate important physiological functions including the neurological system, blood pressure control, hematopoiesis, glucose metabolism and inflammatory responses. The latter highlights the wide therapeutic range of <i>n − </i>3 PUFAs is especially notable considering the implications for controlling inflammatory disorders. Furthermore, the chemistry and dietary sources of omega-3 fatty acids are clarified in this review, which also sheds light on the complex molecular pathways that support the therapeutic efficacy of these fats and their bioavailability. The most recent information on the FDA's approval of omega-3 oils for use in formulation development highlights the compounds' adaptability and potential influence on the development of novel medications.</p><h3>Conclusion</h3><p>A thorough analysis of omega-3 polyunsaturated fatty acids reveals both their remarkable therapeutic potential against a variety of diseases and their essential place in a normal diet. This study adds to the increasing amount of data that supports the use of <i>n</i> − 3 PUFAs in preventative and therapeutic approaches that are meant to improve human health and well-being by clarifying their mechanisms of action and emphasizing their applicability in formulation and development.</p></div>","PeriodicalId":577,"journal":{"name":"Future Journal of Pharmaceutical Sciences","volume":"10 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://fjps.springeropen.com/counter/pdf/10.1186/s43094-024-00667-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141863427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and evaluation of imiquimod-loaded nanoemulsion-based gel for the treatment of skin cancer","authors":"Shital T. Jadhav,&nbsp;Vijay R. Salunkhe,&nbsp;Somnath D. Bhinge,&nbsp;Sandip M. Honmane,&nbsp;Aasha S. Jadhav","doi":"10.1186/s43094-024-00660-y","DOIUrl":"10.1186/s43094-024-00660-y","url":null,"abstract":"<div><h3>Background</h3><p>The human skin, as the body’s largest organ, is particularly sensitive to many chemical mutagens and carcinogens encountered in daily life. Skin cancer has become a notable global health concern, partly due to increased exposure to environmental pollutants and UV rays. Various treatments are available to treat skin cancer. Imiquimod is approved for the treatment of actinic keratosis and basal cell carcinoma. The present investigation aimed to develop nanoemulsion-based gel with imiquimod (2.5% w/w) and carbopol ultrez 10 NF using a modified method to enhance the solubility, permeation, and therapeutic effectiveness of imiquimod to treat skin cancer. Combinations of rose oil and oleic acid, with Tween 20/Propylene glycol as Smix, were used in the formulation. The formulation underwent evaluation for parameters such as % drug content, in vitro drug diffusion studies, viscosity, skin irritation, in vitro cytotoxicity assay (MTT assay) and the DMBA/ croton oil skin cancer in vivo model.</p><h3>Results</h3><p>The formulation showed a minimum globule size of 118 nm, a zeta potential– 56.26 mV, a PDI of 0.378 and a drug content of 99.77%. In vitro drug release exhibited 45.00% of imiquimod release within 8 h, while approximately 34.32% release was found from the commercial cream. The imiquimod-loaded nanoemulsion-based gel showed significant cytotoxicity (<i>p</i> &lt; 0.001) against the A431 cell line compared to Imiquad cream<i>.</i> The IC₅₀ value of the imiquimod-loaded nanoemulsion-based gel was noted to be 10.76 ± 2.54 µg/mL. In vivo results showed a significant reduction in tumor incidence (16.66%), tumor volume (140.26 ± 3.48 mm³), tumor burden (5.50 mm³) and tumor mass (0.66 ± 0.05 g) compared with the DMBA/croton oil carcinogen treatment control group. Histopathological finding showed the absence of keratinized pearls, epidermal hyperplasia, and acanthosis in the formulation treated group.</p><h3>Conclusion</h3><p>The results revealed that the nanoemulsion-based gel, with half the IMQ concentration of the commercial cream and incorporating Carbopol Ultrez 10NF, is a promising method for treating skin carcinogenesis. It potentially reduces dose-dependent side effects and demonstrating enhanced efficacy.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":577,"journal":{"name":"Future Journal of Pharmaceutical Sciences","volume":"10 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://fjps.springeropen.com/counter/pdf/10.1186/s43094-024-00660-y","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141863425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cubosomes: evolving platform for intranasal drug delivery of neurotherapeutics","authors":"Priyanka Gawarkar-Patil,&nbsp;Bhavna Mahajan,&nbsp;Atmaram Pawar,&nbsp;Vividha Dhapte-Pawar","doi":"10.1186/s43094-024-00665-7","DOIUrl":"10.1186/s43094-024-00665-7","url":null,"abstract":"<div><h3>Background</h3><p>As per World Health Organization (WHO) database, neurological and psychiatric disorders constitute a significant and escalating source of morbidity, impacting over one billion lives with a staggering 9 million fatalities. Unfortunately, the magnitude of these disorders remains largely untreated, primarily due to the formidable challenge of the cerebrospinal fluid–brain barrier (CBB), blood–brain barrier (BBB), as well as the blood–cerebrospinal fluid barrier (BCSFB) compromising the central nervous system (CNS) therapies. Thus, there is a need to explore innovative drug delivery platforms capable of overcoming these barriers in order to facilitate effective delivery of therapeutic drugs.</p><h3>Main body of abstract</h3><p>Intranasal drug delivery (INDD) of nanoformulations has emerged as a promising approach, leveraging advantages such as a high surface area, nanoscale particle size, mucoadhesion, noninvasive administration with rapid, and greater drug bioavailability. In this, cubosomal drug delivery (DD) has emerged as a pivotal targeted drug delivery strategy, particularly in the therapy of neurological ailments. Nowadays, researchers and academicians have focused their efforts to tailor cubosomes (CBS) specifically for improving efficacy of central nervous system (CNS) therapies.</p><h3>Conclusion</h3><p>This review gives an idea about current status of neurological disorders (ND), the barriers that restricts CNS drug delivery (BBB), and possible nasal pathways of CBS for effective drug transport. A central focus is placed on intranasal (IN) cubosomal formulations for several NDs, elucidating their potential benefits while addressing existing challenges. In essence, this comprehensive review provides valuable insights into innovative approaches that hold promise for addressing the use and need of IN-CBS in the treatment of NDs.</p></div>","PeriodicalId":577,"journal":{"name":"Future Journal of Pharmaceutical Sciences","volume":"10 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://fjps.springeropen.com/counter/pdf/10.1186/s43094-024-00665-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141736837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adenocarcinoma of unknown primary with TP53 gene polymorphism: a rare case report with literature review","authors":"Raushan Kumar Chaudhary,&nbsp;Uday Venkat Mateti,&nbsp;Jayaprakash Shetty,&nbsp;Prakash Patil,&nbsp;Vinay C. Sangamesh,&nbsp;Vijith Vittal Shetty","doi":"10.1186/s43094-024-00662-w","DOIUrl":"10.1186/s43094-024-00662-w","url":null,"abstract":"<div><h3>Background</h3><p>Cancer of unknown primary (CUP) is an orphan disease generally presented by undifferentiated and aggressive morphological phenotype. The treatment of CUP is solely dependent upon the origin of cancer. Despite extensive diagnostic testing, in most of the cases the primary site remains unidentifiable.</p><h3>Case presentation</h3><p>This case demonstrates a 75-year-old male patient, who initially presented with the complaints of swelling over right side of the neck since 2 months. A cervical lymph node biopsy was taken for immunohistochemistry, which revealed cytokeratin (CK) and CK7 markers to be positive. Computerized tomography (CT) of Thorax showed subcentimetric subpleural nodules in bilateral lungs fields, predominantly in lower lobes (metastatic in nature). A subsequent pulmoCORE 12 gene panel test was recommended, and patient was discharged with tablet gefitinib 250mg and capsule containing vitamins plus minerals. After one month, patient revisited with the pulmoCORE 12 gene test report which revealed polymorphism in <i>TP53</i>. A pathogenic variant of tumor protein p53 (<i>TP53</i>), i.e., p.Glu198Ter (amino acid alteration) and c.592G &gt; T (coding) variant, was detected, which has 17.2% variant allele frequency. There are no treatment guidelines for <i>TP53</i> mutation; therefore, the patient was treated with injection paclitaxel 70mg and carboplatin 100mg for 12 cycles along with palliative radiotherapy of 20 Gy for 5 fractions. The overall prognosis of patient was found to be favorable.</p><h3>Conclusions</h3><p>There is a need for development of comprehensive guidelines and new molecularly targeted therapies for treatment of CUP which can be tailored for each patient and achieve precise therapeutic outcome.</p></div>","PeriodicalId":577,"journal":{"name":"Future Journal of Pharmaceutical Sciences","volume":"10 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://fjps.springeropen.com/counter/pdf/10.1186/s43094-024-00662-w","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141725738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Carbapenem-resistant Acinetobacter baumannii infections among diabetic and non-diabetic patients and possible effective combination treatments","authors":"Aya M. Ghareeb,&nbsp;Marwa M. Raafat,&nbsp;Naglaa S. Bazan,&nbsp;Reham Samir","doi":"10.1186/s43094-024-00661-x","DOIUrl":"10.1186/s43094-024-00661-x","url":null,"abstract":"<div><h3>Background</h3><p>Carbapenems are one of the most noteworthy choices for treating multidrug-resistant <i>Acinetobacter baumannii (A. baumannii)</i>. Currently, carbapenem-resistant <i>A. baumannii</i> (CRAB) represents a healthcare problem worldwide, particularly among diabetic patients who are more susceptible to microbial infections. The aim of this study was to investigate the differences in antibiotic susceptibility profiles, the abundance of carbapenem resistance genes across <i>A. baumannii-</i>infected diabetic and non-diabetic patients, and the antimicrobial activity of different antibiotic combinations on highly resistant isolates.</p><h3>Methods</h3><p>Data of 99 <i>A. baumannii</i>-infected patients were collected during the period from 2018 to 2022 and categorized according to patients’ diabetes status into either diabetic or non-diabetic group. A total of 45 <i>A. baumannii</i> isolates were collected during 2021 and 2022 from the main hospital laboratory to be reidentified and genetically confirmed. Antibiotic susceptibility, including carbapenems, was determined using disc agar diffusion and broth microdilution methods. The isolates were screened for <i>OXA-23, GES, VIM, and NDM</i> carbapenem-resistant genes. Five antibiotic combinations were assessed using the double-disk synergy and checkerboard methods.</p><h3>Results</h3><p>The findings of the current study revealed that multidrug resistance increased gradually, from 56% in 2018 to 95.6% in 2022. Moreover, CRAB increased among diabetics and non-diabetics. Resistance rates of imipenem, meropenem, and doripenem reached 68.8%, 61.8%, and 47.4% in diabetics and 97.9%, 83.3%, and 50% in non-diabetics, respectively. The <i>VIM</i> gene was the most prevalent gene with prevalence rates of 100% and 96.15% in diabetics and non-diabetics, respectively. Moreover, all <i>A. baumannii</i> isolates carried at least two of the selected carbapenem-resistant genes. Across the different used combinations, only the tigecycline-meropenem combination showed synergistic activity in 50% of diabetic and 66.7% of non-diabetic isolates.</p><h3>Conclusions</h3><p>An increased carbapenem resistance was observed among <i>A. baumannii</i>-infected individuals, both diabetic and non-diabetic. The MEM/TCG combination was the only one that showed synergistic or additive effects against highly resistant isolates making it a viable alternative treatment option.</p></div>","PeriodicalId":577,"journal":{"name":"Future Journal of Pharmaceutical Sciences","volume":"10 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://fjps.springeropen.com/counter/pdf/10.1186/s43094-024-00661-x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141725737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design, synthesis and evaluation of new methyl piperazine derivatives as anticancer agents","authors":"Mahaveer Singh,&nbsp;Hemant R. Jadhav,&nbsp;Amit Choudhary,&nbsp;Pankaj Wadhwa","doi":"10.1186/s43094-024-00663-9","DOIUrl":"10.1186/s43094-024-00663-9","url":null,"abstract":"<div><h3>Background</h3><p>To overcome the problem of side effects and toxicity, development of new anticancer agents is needed. Recently, piperidine salicylanilide derivatives with nanomolar epidermal growth factor receptor (EGFR) inhibitory and cytotoxicity activity have been reported. In the present study effect of replacing piperidine in reported piperidine salicylanilide with <i>N</i>-methyl piperazine and changing substituent’s of phenyl ring at other end on anticancer activity have been explored. A series of sixteen methyl piperazine incorporated phenyl benzamide and phenyl methanone derivatives have been synthesized and tested in a panel of three cancer cell lines (adenocarcinomic human alveolar basal epithelial cells (A-549), human colon carcinoma (HCT-116) and human pancreatic carcinoma (MIAPaCa-2)), using gefitinib as standard. Further, to study the probable mechanism, due to their structural similarity with EGFR inhibitors, docking interactions with EGFR active site were observed using Schrodinger suite.</p><h3>Result</h3><p>The results indicated that most of the compounds showed promising activity; out of which, compound A-11 was most active having cytotoxicity much better than that of gefitinib. It showed IC₅₀ value of 5.71 µM against A-549 cell line, 4.26 µM against HCT-116 colon cancer line and 31.36 µM against MIAPaCa-2 cell line.</p><h3>Conclusion</h3><p>It was found that these compounds fit well in the active site and may be exhibiting anticancer activity via EGFR inhibition.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><img></picture></div></div></figure></div></div>","PeriodicalId":577,"journal":{"name":"Future Journal of Pharmaceutical Sciences","volume":"10 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://fjps.springeropen.com/counter/pdf/10.1186/s43094-024-00663-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141624170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}