Antimycobacterial mechanism of vanillin involves disruption of cell-surface integrity, virulence attributes, and iron homeostasis

AbstractObjective/BackgroundTuberculosis (TB) remains a global threat, claiming one-third of the population annually. The ever increasing emergence of multidrug-resistant TB (MDR-TB) is the major impediment to effective anti-TB therapy. Under such circumstances, deciphering the antimycobacterial potential of natural compounds has gained considerable prominence. This study evaluated the antimycobacterial activity of vanillin (Van), a natural food-flavoring agent and preservative, along with its potential mechanisms of action.MethodsDrug susceptibilities were performed using broth microdilution, spot, and filter-disc assays. Membrane damage was studied by nitrocefin hydrolysis and electron microscopy. Virulence attributes were assessed by biofilm formation and cell adherence. Iron availability was estimated by enzymatic (ferroxidase) assay.ResultsWe found that the antimycobacterial activity of Van against Mycobacterium smegmatis (a surrogate of Mycobacterium tuberculosis) is 125μg/mL. Additionally, we observed disruption of membrane homeostasis in the presence of Van, as revealed by enhanced membrane permeability and transmission electron microscopy images showing a disturbed cell envelope. Concomitant with our findings, we also observed that Van leads to enhanced drug susceptibility to membrane targeting known anti-TB drugs. Furthermore, Van affects significant virulence traits of Mycobacterium by inhibiting biofilm formation and cell adhesion. Finally, we observed that Van disrupted iron homeostasis as displayed by hypersensitivity to iron deprivation.ConclusionThe results established for the first time that Van could be an effective antimycobacterial agent that could be exploited further in treating mycobacterial infections

Brain tumor stem cells: Role in neuro-oncogenesis and therapeutic implications

Malignant brain tumors are notorious for high morbidity and mortality. Our deficient understanding of brain tumor pathogenesis is reflected in our inability to cure this disease. Treatment remains palliative at best. The cancer stem cell hypothesis of brain tumors promises to consolidate many observations which have previously eluded neuroscientists and may reveal why aberrations in developmental programs are among the commonest findings in brain tumors. It is ironic that brain ontogeny and cancer - two processes with very different outcomes - exploit similar mechanisms to multiply, migrate,and survive. Implications of this hypothesis extend beyond mere academic interest. It may explain our current failures in the clinic and sets the stage for novel therapeutic paradigms aimed at altering the developmental adaptations of brain malignancies

Therapeutic Potential of Dietary Phenolic Acids

Although modern lifestyle has eased the quality of human life, this lifestyle’s related patterns have imparted negative effects on health to acquire multiple diseases. Many synthetic drugs are invented during the last millennium but most if not all of them possess several side effects and proved to be costly. Convincing evidences have established the premise that the phytotherapeutic potential of natural compounds and need of search for novel drugs from natural sources are of high priority. Phenolic acids (PAs) are a class of secondary metabolites spread throughout the plant kingdom and generally involved in plethora of cellular processes involved in plant growth and reproduction and also produced as defense mechanism to sustain various environmental stresses. Extensive research on PAs strongly suggests that consumption of these compounds hold promise to offer protection against various ailments in humans. This paper focuses on the naturally derived PAs and summarizes the action mechanisms of these compounds during disease conditions. Based on the available information in the literature, it is suggested that use of PAs as drugs is very promising; however more research and clinical trials are necessary before these bioactive molecules can be made for treatment. Finally this review provides greater awareness of the promise that natural PAs hold for use in the disease prevention and therapy

Antimicrobial potential of epigallocatechin-3-gallate (EGCG): a green tea polyphenol

Abstract: The compounding problem of microbial resistance has become a global threat nowadays and demands urgent attention. Given the limited number of clinically proven drugs available, reversion towards compounds from natural resources have become renewed source of interest. Utilization of novel and potent antimicrobial agents with different targets can act as accessories to antibiotic therapy. Considerable amount of research has been conducted on the various advantages of secondary metabolites produced by different plants. Among these, polyphenols have come into sight over the past few decades as a potential source to promote human health. This article summarizes the various health benefits of EGCG, the major component of green tea polyphenols with more emphasis on the anti-microbial properties of EGCG

Cellular energy status is indispensable for perillyl alcohol mediated abrogated membrane transport in Candida albicans

The prevalence of fungal infections and their resistance patterns in fungal isolates from large number of patients with impaired immunity still remains poorly monitored. In spite of significant advances being made in the improvement of antifungal drugs, only a limited number of antifungal drugs are currently available. The present study aimed to gain further mechanistic insights into the previously described anticandidal activity of natural monoterpenoid, perillyl alcohol (PA). We found that cellular transport across cell membrane was abrogated in presence of PA. This was demonstrated by dose and time dependent enhanced cellular leakage accompanied by inhibited sodium and potassium cellular transport. In addition, we found disrupted pH homeostasis which was depicted by enhanced extracellular pH. We further observed that mitochondrial energy status is highly integrated with the antifungal activity of PA. This was evident from inhibited propidium iodide (PI) uptake in presence of sodium azide and di-nitro phenol (DNP) which showed no fluorescence when treated with PA. Moreover, we observed that PA leads to disrupted mitochondrial membrane potential. Additional cell death hallmarks in response to PA such as nuclear fragmentation was also observed with 4\u27,6-diamidino-2-phenylindole (DAPI) staining. Taken together, PA is a novel candidate that deserves further attention to be exploited as effective antifungal agent of pharmacological interest

Guideline Based Algorithmic Approach for the Management of Renal and Ureteric Calculi

Urolithiasis is a global pathology with increasing prevalence rate. The surgical management of kidney and ureteral stones is based on the stone location, size, the patient’s preference and the institutional availability of various modalities. To date, the available modalities in the management of urolithiasis includes external shock wave lithotripsy (ESWL), percutaneous nephrolithotomy (PNL), ureterorenoscopy (URS) including flexible and semirigid ureteroscopy. Tremendous technological advancement in the urological armamentarium has happened since its inception leading to multiple acceptable modalities for the treatment of a particular stone. In accordance with the available recommendations from various institutions and the newer evidence we recommend that the initial choice of modality for the treatment of a renal calculus depends on the stone size and whether the location is lower pole or not. For lower pole stones upto 20 mm PNL and RIRS is efficient irrespective of location while ESWL should only be considered for lower pole stones upto 10 mm. For stones larger than 20 mm mini PNL is effective for stones upto 40 mm while RIRS holds acceptable efficiency for stones not larger than 30 mm. For stones larger than 40 mm standard PNL only should be considered if single stage treatment is attempted

Laparoscopy Versus Laparotomy in the Management of Ectopic Pregnancy

Objective: To compare the outcome of laparoscopy with laparotomy in the management of ectopic pregnancy (EP), both ruptured and un-ruptured. Patients and Methods: This cross-sectional study was conducted in Department of obstetrics and gynecology at multiple centers in Sahiwal, Bahawalpur and Multan, during the period from January 2015 to June 2017. Total no. of 167 patients of ectopic pregnancy were included in our study. Of these 167 patients, 32 came with ruptured ectopic pregnancy and other 135 with un-ruptured EP. Following outcome variables were collected; operative time, complications, estimated blood loss and postoperative hospital stay. Mean and standard deviation was calculated for demographic variables while frequency and percentage was calculated for outcome variables and association of these variables with groups was checked using computer software SPSS version 16. p value < 0.05 was considered as significant. Results: Out of total 167 patients, ruptured EP was found in 19.2% and non-ruptured in 80.8% patients. Regarding blood transfusion and need of analgesia, significant association (p=0.000) was found between laparoscopy and laparotomy. As compared to laparotomy, during laparoscopy large number of patients did not require blood transfusion ((95.3%) and analgesia (64.1%). Regarding total operating time, duration of hospital’s stay and estimated blood loss, significant difference (p=0.000) was found between the two groups. Conclusion: Postoperative outcomes suggested that laparoscopy proved to be more efficient regarding blood loss, need for blood transfusion, need for analgesia and duration of postoperative hospital stay as compared to laparotomy.&nbsp

Potential of AI-Driven Chatbots in Urology: Revolutionizing Patient Care Through Artificial Intelligence

Purpose of Review Artificial intelligence (AI) chatbots have emerged as a potential tool to transform urology by improving patient care and physician efficiency. With an emphasis on their potential advantages and drawbacks, this literature review offers a thorough assessment of the state of AI-driven chatbots in urology today. Recent Findings The capacity of AI-driven chatbots in urology to give patients individualized and timely medical advice is one of its key advantages. Chatbots can help patients prioritize their symptoms and give advice on the best course of treatment. By automating administrative duties and offering clinical decision support, chatbots can also help healthcare providers. Before chatbots are widely used in urology, there are a few issues that need to be resolved. The precision of chatbot diagnoses and recommendations might be impacted by technical constraints like system errors and flaws. Additionally, issues regarding the security and privacy of patient data must be resolved, and chatbots must adhere to all applicable laws. Important issues that must be addressed include accuracy and dependability because any mistakes or inaccuracies could seriously harm patients. The final obstacle is resistance from patients and healthcare professionals who are hesitant to use new technology or who value in-person encounters. Summary AI-driven chatbots have the potential to significantly improve urology care and efficiency. However, it is essential to thoroughly test and ensure the accuracy of chatbots, address privacy and security concerns, and design user-friendly chatbots that can integrate into existing workflows. By exploring various scenarios and examining the current literature, this review provides an analysis of the prospects and limitations of implementing chatbots in urology.publishedVersio