Multidrug resistance is a serious problem in modern medicine and the reason for the failure of various therapies. A particularly important problem is the occurrence of multidrug resistance in cancer therapies which affects many cancer patients. Observations on the effect of metformin-a well-known hypoglycemic drug used in the treatment of type 2 diabetes-on cancer cells indicate the possibility of an interaction of this substance with drugs already used and, as a result, an increase in the sensitivity of cancer cells to cytostatics. The aim of this study was to evaluate the effect of metformin on the occurrence of multidrug resistance of breast cancer cells. The MCF-7-sensitive cell line and the MCF-7/DX cytostatic-resistant cell line were used for this study. WST-1 and LDH assays were used to evaluate the effects of metformin and doxorubicin on cell proliferation and viability. The effect of metformin on increasing the sensitivity of MCF-7 and MCF-7/DX cells to doxorubicin was evaluated in an MDR test. The participation of metformin in increasing the sensitivity of resistant cells to the effect of the cytostatic (doxorubicin) has been demonstrated.

BACKGROUND: Antimicrobial resistance (AMR) poses a global health threat, with lower-middle-income countries bearing a disproportionate burden. Surveillance of AMR under a One Health framework is needed to elucidate the associations among clinical, animal, and environmental AMR. This review aimed to describe the state of AMR in Ghana, focusing on One Health.
METHODS: This review utilized the PRISMA guidelines and major databases to systematically search and analyze AMR in Ghana published from 1 January 2014 to 1 May 2023.
RESULTS: Out of the 48 articles that met the inclusion criteria, 28 studies were conducted on humans, 14 studies involved animals, and 6 studies focused on the environment. A total of 48 different pathogens were identified across the human, animal, and environmental sectors, with the most common being Escherichia coli (67%, n = 32), Klebsiella spp. (52%, n = 25), Pseudomonas spp. (40%, n = 19), and Salmonella spp. (38%, n = 18). Generally, a high prevalence of antibiotic resistance was observed among various bacterial species across the sectors. These bacteria exhibited resistance to commonly used antibiotics, with resistance to ampicillin and tetracycline exceeding 80%, and multidrug resistance (MDR) ranging from 17.6% in Shigella spp. to 100% in Acinetobacter spp.
CONCLUSIONS: This review reaffirms the significant challenge of AMR in Ghana, with a high prevalence observed in the human, animal, and environmental sectors. Key pathogens (e.g., Staphylococcus aureus and Escherichia coli) found across the sectors emphasize the urgent need for a One Health approach to tackle AMR in Ghana.

The development of antibiotic resistance compromises the effectiveness of our most effective defenses against bacterial infections, presenting a threat to global health. To date, a large number of research articles exist in the literature describing the case reports associated with extensively drug-resistant (XDR) and multidrug-resistant (MDR) bacterial strains. However, these findings are scattered, making it time-consuming for researchers to locate promising results and there remains a need for a comparative study to compile these case reports from various geographical regions including the Kingdom of Saudi Arabia. Additionally, no study has yet been published that compares the genetic variations and case reports of MDR and XDR strains identified from Saudi Arabia, the Middle East, Central Europe, and Asian countries. This study attempts to provide a comparative analysis of several MDR and XDR case reports from Saudi Arabia alongside other countries. Furthermore, the purpose of this work is to demonstrate the genetic variations in the genes underlying the resistance mechanisms seen in MDR and XDR bacterial strains that have been reported in Saudi Arabia and other countries. To cover the gap, this comprehensive review explores the complex trends in antibiotic resistance and the growing risk posed by superbugs. We provide context on the concerning spread of drug-resistant bacteria by analyzing the fundamental mechanisms of antibiotic resistance and looking into individual case reports. In this article, we compiled various cases and stories associated with XDR and MDR strains from Saudi Arabia and various other countries including China, Egypt, India, Poland, Pakistan, and Taiwan. This review will serve as basis for highlighting the growing threat of MDR, XDR bacterial strains in Saudi Arabia, and poses the urgent need for national action plans, stewardship programs, preventive measures, and novel antibiotics research in the Kingdom.

Drug repurposing, rebranding an existing drug for a new therapeutic indication, is deemed a beneficial approach for a quick and cost-effective drug discovery process by skipping preclinical, Phase 1 trials and pharmacokinetic studies. Several psychotropic drugs, including selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs), were studied for their potential application in different diseases, especially in cancer therapy. Fluoxetine (FLX) is one of the most prescribed psychotropic agents from the SSRIs class for the treatment of several neuropsychiatric disorders with a favorable safety profile. FLX exhibited different oncolytic effects via mechanisms distinct from its main serotonergic activity. Taking advantage of its ability to rapidly penetrate the blood-brain barrier, FLX could be particularly useful in brain tumors. This was proved by different in vitro and in vivo experiments using FLX as a monotherapy or combination with temozolomide (TMZ) or radiotherapy. In this review of the literature, we summarize the potential pleiotropic oncolytic roles of FLX against different cancers, highlighting the multifaceted activities of FLX and its ability to interrupt cancer proliferation via several molecular mechanisms and even surmount multidrug resistance (MDR). We elaborated on the successful synergistic combinations such as FXR/temozolomide and FXR/raloxifene for the treatment of glioblastoma and breast cancer, respectively. We showcased beneficial pharmaceutical trials to load FLX onto carriers to enhance its safety and efficacy on cancer cells. This is the first review article extensively summarizing all previous FLX repurposing studies for the management of cancer.

UNASSIGNED: Pseudomonas aeruginosa (PA) is a Gram-negative bacterium that can cause a wide range of severe infections in immunocompromised patients. The most difficult challenge is due to its ability to rapidly develop multi drug-resistance. New strategies are urgently required to improve the outcome of patients with PA infections. The present patent review highlights the new molecules acting on different targets involved in the antibiotic resistance.
UNASSIGNED: This review offers an insight into new potential PA treatment disclosed in patent literature. From a broad search of documents claiming new PA inhibitors, we selected and summarized molecules that showed in vitro and in vivo activity against PA spp. in the period 2020 and 2023. We collected the search results basing on the targets explored.
UNASSIGNED: This review examined the main patented compounds published in the last three years, with regard to the structural novelty and the identification of innovative targets. The main areas of antibiotic resistance have been explored. The compounds are structurally unrelated to earlier antibiotics, characterized by a medium-high molecular weight and the presence of heterocycle rings. Peptides and antibodies have also been reported as potential alternatives to chemical treatment, hereby expanding the therapeutic possibilities in this field.

Reversing the multiple drug resistance (MDR) arising from the overexpression of the efflux transporters often fails mainly due to the high toxicity or the poor water solubility of the inhibitors of these transporters. Here, we demonstrate the delivery of an inhibitor targeting three ABC transporters (ABCB1, ABCC1 and ABCG2) directly to the cell membrane using membrane-fusing vehicles (MFVs). Three different transfected MDCK II cell lines, along with parental cells, were used to investigate the inhibitory effect of cyclosporine A (CsA) in solution versus direct delivery to the cell membrane. CsA-loaded MFVs successfully reversed MDR for all three investigated efflux transporters at significantly lower concentrations compared with CsA in solution. Results showed a 15-fold decrease in the IC50 value for ABCB1, a 7-fold decrease for ABCC1 and an 11-fold decrease for ABCG2. We observed binding site specificity for ABCB1 and ABCG2 transporters. Lower concentrations of empty MFVs along with CsA contribute to the inhibition of Hoechst 33342 efflux. However, higher concentrations of CsA along with the high amount of MFVs activated transport via the H-binding site. This supports the conclusion that MFVs can be useful beyond their role as delivery systems and also help to elucidate differences between these transporters and their binding sites.

The global emergence of antimicrobial resistance to multiple antibiotics has recently become a significant concern. Gram-negative bacteria, known for their ability to acquire mobile genetic elements such as plasmids, represent one of the most hazardous microorganisms. This phenomenon poses a serious threat to public health. Notably, the significance of tigecycline, a member of the antibiotic group glycylcyclines and derivative of tetracyclines has increased. Tigecycline is one of the last-resort antimicrobial drugs used to treat complicated infections caused by multidrug-resistant (MDR) bacteria, extensively drug-resistant (XDR) bacteria or even pan-drug-resistant (PDR) bacteria. The primary mechanisms of tigecycline resistance include efflux pumps\' overexpression, tet genes and outer membrane porins. Efflux pumps are crucial in conferring multi-drug resistance by expelling antibiotics (such as tigecycline by direct expelling) and decreasing their concentration to sub-toxic levels. This review discusses the problem of tigecycline resistance, and provides important information for understanding the existing molecular mechanisms of tigecycline resistance in Enterobacterales. The emergence and spread of pathogens resistant to last-resort therapeutic options stands as a major global healthcare concern, especially when microorganisms are already resistant to carbapenems and/or colistin.

Two new phenylspirodrimanes, stachybotrins K and L (1 and 2), together with eight known analogues (3-10), were isolated from deep-sea-derived Stachybotrys sp. MCCC 3A00409. Their structures were determined by extensive NMR data and mass spectroscopic analysis. Absolute configurations of new compounds were determined through a comparison of their circular dichroism (CD) spectra with other reported compounds. The possible reversal effects of all compounds were assayed in the resistant cancer cell lines. Stachybotrysin B (8) can reverse multidrug resistance (MDR) in ABCB1-overexpression cells (KBv200, Hela/VCR) at the non-cytotoxic concentration. Doxorubicin accumulation assay and molecular-docking analysis reveal that the mechanism of its reversal MDR effect may be related to the increase in the intracellular concentration of substrate anticancer drugs.

Cancer is attributed to uncontrolled cell growth and is among the leading causes of death with no known effective treatment while complex tumor microenvironment (TME) and multidrug resistance (MDR) are major challenges for developing an effective therapeutic strategy. Advancement in cancer immunotherapy has been limited by the over-activation of the host immune response that ultimately affects healthy tissues or organs and leads to a feeble response of the patient\'s immune system against tumor cells. Besides, traditional herbal medicines (THM) have been well-known for their essential role in the treatment of cancer and are considered relatively safe due to their compatibility with the human body. Yet, poor solubility, low bio-availability, and lack of understanding about their pathophysiological mechanism halt their clinical application. Moreover, considering the complex TME and drug resistance, the most precarious and least discussed concerns for developing THM-based nano-vaccination, are identification of specific biomarkers for drug inhibitory protein and targeted delivery of bioactive ingredients of THM on the specific sites in tumor cells. The concept of THM-based nano-vaccination indicates immunomodulation of TME by THM-based bioactive adjuvants, exerting immunomodulatory effects, via targeted inhibition of key proteins involved in the metastasis of cancer. However, this concept is at its nascent stage and very few preclinical studies provided the evidence to support clinical translation. Therefore, we attempted to capsulize previously reported studies highlighting the role of THM-based nano-medicine in reducing the risk of MDR and combating complex tumor environments to provide a reference for future study design by discussing the challenges and opportunities for developing an effective and safe therapeutic strategy against cancer.

Bacterial infections continue to pose a significant global health challenge, with the emergence of multidrug-resistant (MDR) bacteria and biofilms further complicating treatment options. The rise of pan-resistant bacteria, coupled with the slow development of new antibiotics, highlights the urgent need for new therapeutic strategies. Nanotechnology-based biosensors offer fast, specific, sensitive, and selective methods for detecting and treating bacteria; hence, it is a promising approach for the diagnosis and treatment of MDR bacteria. Through mechanisms, such as destructive bacterial cell membranes, suppression of efflux pumps, and generation of reactive oxygen species, nanotechnology effectively combats bacterial resistance and biofilms. Nano-biosensors and related technology have demonstrated their importance in bacteria diagnosis and treatment, providing innovative ideas for MDR inhibition. This review focuses on multiple nanotechnology approaches in targeting MDR bacteria and eliminating antimicrobial biofilms, highlighting nano-biosensors via photodynamics-based biosensors, eletrochemistry biosensors, acoustic-dynamics sensors, and so on. Furthermore, the major challenges, opportunities of multi-physical-field biometrics-based biosensors, and relevant nanotechnology in MDR bacterial theranostics are also discussed. Overall, this review provides insights and scientific references to harness the comprehensive and diverse capabilities of nano-biosensors for precise bacteria theranostics and MDR inhibition.