Anti-fungal peptides: an emerging category with enthralling therapeutic prospects in the treatment of candidiasis.

Candida infections, particularly invasive candidiasis, pose a serious global health threat. Candida albicans is the most prevalent species causing candidiasis, and resistance to key antifungal drugs, such as azoles, echinocandins, polyenes, and fluoropyrimidines, has emerged. This growing multidrug resistance (MDR) complicates treatment options, highlighting the need for novel therapeutic approaches. Antifungal peptides (AFPs) are gaining recognition for their potential as new antifungal agents due to their diverse structures and functions. These natural or recombinant peptides can effectively target fungal virulence and viability, making them promising candidates for future antifungal development. This review examines infections caused by Candida species, the limitations of current antifungal treatments, and the therapeutic potential of AFPs. It emphasizes the importance of identifying novel AFP targets and their production for advancing treatment strategies. By discussing the therapeutic development of AFPs, the review aims to draw researchers' attention to this promising field. The integration of knowledge about AFPs could pave the way for novel antifungal agents with broad-spectrum activity, reduced toxicity, targeted action, and mechanisms that limit resistance in pathogenic fungi, offering significant advancements in antifungal therapeutics.

Characterization of Swarna Bhasma and Swarnaprash and Determination of Antimicrobial Properties Against Gut-Pathobiont and Symbiont.

Ayurveda has a long-standing tradition of healthcare in Southeast Asia. Swarnaprash, a classical Ayurveda preparation, is commonly given as the pre-lacteal feed to neonates to prevent labor-related complications and infections. It comprises incinerated gold particles (InAuP/Swarna Bhasma), honey (Madhu), and clarified butter oil (CBO/Cow Ghrita). This in vitro study aimed to evaluate the therapeutic potential of the individual ingredients and combinations of Swarnaprash against selected neonatal gut pathobionts and symbionts. The study employed sophisticated instruments, including SEM with EDAX and X-ray diffraction analysis, to investigate the shape and structural disparities in the ingredients of Swarnaprash. The reported size of gold particles in Swarnaprash ranges from 0.6 to 9.5 µm. These particles are relatively smaller than those in Swarna Bhasma but larger than synthetic gold particles. Swarnaprash demonstrated both bactericidal and bacteriostatic activity against selected neonatal gut pathobionts, with the largest inhibition zones observed for P. aeruginosa and S. Typhi. It surpassed the individual efficacy of its components-Prash, InAuPs, honey, or CBO alone. Notably, Swarnaprash did not affect the selected beneficial gut bacteria. The results warrant further in vivo and clinical studies to explore the effects of Swarnaprash on neonatal gut flora, which would provide vital information for research in neonatal healthcare.

Cellulase exhibited a therapeutic potential to inhibit Salmonella enterica serovar Typhi biofilm by targeting multiple regulatory proteins of biofilm.

Biofilm-mediated Salmonella enterica serovar Typhi (Salmonella Ser. Typhi) infections are a growing global health issue due to the formation of antibiotic resistance. The study aimed to discover some of the druggable target proteins of Salmonella Ser. Typhi biofilm and antibiofilm enzyme to prevent Salmonella Ser. Typhi biofilm-mediated infection. Enzymatic therapy has demonstrated effective therapeutic results against bacterial infections due to its specificity and high binding capacity to the target. Therefore, this study focused on the computational interaction between the cellulase enzyme and Salmonella Ser. Typhi biofilm targets proteins with help of the various computational experiments such as ADMET (absorption, distribution, metabolism, excretion, and toxicity), protein-protein interactions, MMGBSA, etc. Further, in vitro validations of the typhoidal biofilm and cellulose presence in Salmonella Ser. Typhi biofilm was conducted using Scanning Electron Microscopy (SEM), Fourier transform infrared spectroscopy, and Raman analysis. Additionally, a minimum biofilm inhibitory concentration assay for cellulase was conducted and find out the optimized cellulase concentration which showed its inhibitory effect on the Salmonella Ser. Typhi. The cellulase antibiofilm effect was analyzed with the help of SEM analysis. Further, the cellulose content in Salmonella Ser. Typhi was quantified before and after treatment of cellulase enzyme. As a result, 58.82 % cellulose content was decreased due to cellulase treatment in Salmonella Ser. Typhi. From the seven selected typhoidal biofilm regulatory proteins of Salmonella Ser. Typhi, we identified only five potential druggable targets: BcsA, CsgE, OmpR, CsgF, and CsgD. The BcsA protein is responsible for cellulose production in Salmonella Ser. Typhi biofilm. Consequently, cellulose worked as a fascinating drug target in Salmonella Ser. Typhi biofilm. Therefore, we used cellulase as a potential antibiofilm enzyme for target-based disruption of biofilm. The cellulase showed a high binding affinity with all five identified target proteins [BcsA(-205.62 kcal/mol) > CsgE(-108.20 kcal/mol) > OmpR(-107.58 kcal/mol) > CsgF(-73.74 kcal/mol) > CsgD(-66.61 kcal/mol)] in the protein-protein interaction analysis. Our computational analysis suggests that the cellulase enzyme may be used as a potential antibiofilm enzyme against Salmonella Ser. Typhi biofilm.

In silico-driven identification and experimental confirmation of antifungal proteins (AFPs) against Candidaalbicans.

Mycoses infect millions of people annually across the world. The most common mycosis agent, Candida albicans is responsible for a great deal of illness and death. C. albicans infection is becoming more widespread and the current antifungals polyenes, triazoles, and echinocandins are less efficient against it. Investigating antifungal peptides (AFPs) as therapeutic is gaining momentum. Therefore, we used MALDI-TOF/MS analysis to identify AFPs and protein-protein docking to analyze their interactions with the C. albicans target protein. Some microorganisms with strong antifungal action against C. albicans were selected for the isolation of AFPs. Using MALDI-TOF/MS, we identified 3 AFPs Chitin binding protein (ACW83017.1; Bacillus licheniformis), the bifunctional protein GlmU (BBQ13478.1; Stenotrophomonas maltophilia), and zinc metalloproteinase aureolysin (BBA25172.1; Staphylococcus aureus). These AFPs showed robust interactions with C. albicans target protein Sap5. We deciphered some important residues in identified APFs and highlighted interaction with Sap5 through hydrogen bonds, protein-protein interactions, and salt bridges using protein-protein docking and MD simulations. The three discovered AFPs-Sap5 complexes exhibit different levels of stability, as seen by the RMSD analysis and interaction patterns. Among protein-protein interactions, the remarkable stability of the BBQ25172.1-2QZX complex highlights the role of salt bridges and hydrogen bonds. Identified AFPs could be further studied for developing successful antifungal candidates and peptide-based new antifungal therapeutic strategies as fresh insights into addressing antifungal resistance also.

Physicochemical analysis of chitosan oligosaccharide revealed its usefulness in effective delivery of drugs.

Chitosan oligosaccharides are biopolymers with a wide range of potential applications in various fields. This biopolymer is diverse and promising, and current research is investigating its capabilities for improved drug delivery. As chitosan oligosaccharide has the potential to be used as a drug delivery option, the purpose of this study was to examine its physicochemical characteristics and its potential for drug delivery. In this study, the pharmacokinetic properties of chitosan oligosaccharide were studied through Insilco investigation, which revealed that it is an extremely soluble and effective drug delivery candidate because it does not inhibit CYP isoenzymes and has a log Kp of -12.10 cm/s. It belongs to toxicity class 6 for acute oral toxicity, with an average similarity of 87.5% and a prediction accuracy of 70.97%. Additionally, XRD peak analysis revealed that the material was amorphous, as the peak appeared at 2θ = 24.62°, indicating the absence of well-defined crystalline areas. This characteristic makes the material more suitable for customization in many applications such as drug delivery and tissue engineering. FTIR, SEM, and TGA analysis were performed to gain a better understanding. These findings also emphasize the distinctive qualities and benefits of the oligosaccharides in this domain. Application of chitosan oligosaccharides in the development of efficient drug delivery systems. In the future, it would be more effective, targeted, and safe, with potent therapeutic efficacy for drug delivery.

Jejunal Angiodysplasia as an Unusual Cause of Hemorrhage After Hepaticojejunostomy.

Ectopic variceal bleeding is a rare cause of postoperative hemorrhage following hepaticojejunostomy and should be differentiated from other causes such as pseudoaneurysms or ulcers. Uncommon complications post-hepaticojejunostomy demand scrupulous attention, and this case report reveals a seldom-documented scenario of jejunal angiodysplasia as an elusive cause of postoperative bleeding. Through a comprehensive examination of the patient's clinical trajectory, diagnostic challenges, and subsequent management, this report contributes to the expanding knowledge base on atypical vascular complications in surgical settings.

Combinatorial therapeutic enzymes to combat multidrug resistance in bacteria.

AIMS: Antibiotic resistance including multidrug resistance (MDR) is a negative symbol to the human health system because it loses the capability to treat infections. Unfortunately, the available antibiotics do not show an effective therapeutic response against bacterial infections. In the situation of global antibiotic unresponsiveness, enzymatic therapy especially in combinatorial form seems an effective approach to control bacterial infection and combat resistance. The article is important because it focuses on combinatorial enzymatic therapy that has multiple properties (effective antibacterial performances, antibiofilm capacity, immunomodulators, targeted actions, synergistic actions, multiple targeting, and resistance-proof properties) and can address antibiotic resistance effectively. MATERIALS AND METHODS: We searched the related topics with Pubmed, Scopus, and Google Scholar databases and finally 73 relevant papers were reviewed in detail and cited in this article. KEY FINDINGS: Discusses properties of combinatorial therapeutic enzymes made it an accomplished means over antibiotic therapy. This article discusses the need for combinatorial enzymatic therapy against bacterial infection, its distinguished features, and properties with multi-mechanistic antibacterial action. It discussed the European Medicine Agency and Food and Drug Administration-approved therapeutic enzymes (antibacterial and antibiofilm). SIGNIFICANCE: This article provided the possible combination of the enzyme that may be used as an antibacterial agent along with limitations and future scope of combinatorial antibacterial enzymatic agents. This article could draw the attention of researchers to combinatorial therapeutic enzymatic molecules as effective and futuristic therapy to overcome the problem of multiple antibiotic resistance in bacteria.

Nanomaterials-Based Hybrid Bioink Platforms in Advancing 3D Bioprinting Technologies for Regenerative Medicine.

3D bioprinting is recognized as the ultimate additive biomanufacturing technology in tissue engineering and regeneration, augmented with intelligent bioinks and bioprinters to construct tissues or organs, thereby eliminating the stipulation for artificial organs. For 3D bioprinting of soft tissues, such as kidneys, hearts, and other human body parts, formulations of bioink with enhanced bioinspired rheological and mechanical properties were essential. Nanomaterials-based hybrid bioinks have the potential to overcome the above-mentioned problem and require much attention among researchers. Natural and synthetic nanomaterials such as carbon nanotubes, graphene oxides, titanium oxides, nanosilicates, nanoclay, nanocellulose, etc. and their blended have been used in various 3D bioprinters as bioinks and benefitted enhanced bioprintability, biocompatibility, and biodegradability. A limited number of articles were published, and the above-mentioned requirement pushed us to write this review. We reviewed, explored, and discussed the nanomaterials and nanocomposite-based hybrid bioinks for the 3D bioprinting technology, 3D bioprinters properties, natural, synthetic, and nanomaterial-based hybrid bioinks, including applications with challenges, limitations, ethical considerations, potential solution for future perspective, and technological advancement of efficient and cost-effective 3D bioprinting methods in tissue regeneration and healthcare.

Innovative Approaches to Address the Technical Challenge of Hernial Sac Distension Due to Pneumoperitoneum in the Synchronous Management of Complex Hernias in Individuals With Morbid Obesity.

Although repairing ventral hernias in individuals who have undergone bariatric surgery is a common practice, persistent technical intricacies and controversies surround their management. Concurrently, addressing ventral hernias in morbidly obese patients undergoing bariatric surgery presents a significant surgical challenge, amplified by the larger intraperitoneal cavities and the presence of large hernial sacs. This technical report introduces two innovative techniques to alleviate the challenge of hernia sac distension due to pneumoperitoneum associated with simultaneous bariatric surgery and ventral hernia repair using laparoscopic technique. The methods are designed to address the complexities of the procedures, making their simultaneous execution feasible and safe. The goal is to eliminate the need for two separate interventions while ensuring the outcomes of each procedure remain uncompromised. The larger intraperitoneal cavities and the presence of large hernial sacs are managed successfully, demonstrating the feasibility and safety of the introduced methods. Importantly, the simultaneous execution of both procedures does not compromise the outcomes of either intervention. Concurrently managing ventral hernias in morbidly obese patients undergoing bariatric surgery requires innovative solutions to overcome technical challenges. The introduction of these two novel techniques proves to be a valuable approach, making simultaneous execution feasible and safe. Eliminating the need for two separate interventions streamlines the surgical process without compromising the outcomes of either bariatric surgery or ventral hernia repair.

Engineered nanoparticles in non-invasive insulin delivery for precision therapeutics of diabetes.

Diabetes mellitus is a chronic disease leading to the death of millions a year across the world. Insulin is required for Type 1, Type 2, and gestational diabetic patients, however, there are various modes of insulin delivery out of which oral delivery is noninvasive and convenient. Moreover, factors like insulin degradation and poor intestinal absorption play a crucial role in its bioavailability and effectiveness. This review discusses various types of engineered nanoparticles used in-vitro, in-vivo, and ex-vivo insulin delivery along with their administration routes and physicochemical properties. Injectable insulin formulations, currently in use have certain limitations, leading to invasiveness, low patient compliance, causing inflammation, and side effects. Based on these drawbacks, this review emphasizes more on the non-invasive route, particularly oral delivery. The article is important because it focuses on how engineered nanoparticles can overcome the limitations of free therapeutics (drugs alone), navigate the barriers, and accomplish precision therapeutics in diabetes. In future, more drugs could be delivered with a similar strategy to cure various diseases and resolve challenges in drug delivery. This review significantly describes the role of various engineered nanoparticles in improving the bioavailability of insulin by protecting it from various barriers during non-invasive routes of delivery.

LC-MS/MS profiling and analysis of Bacillus licheniformis extracellular proteins for antifungal potential against Candida albicans.

Candida albicans, a significant human pathogenic fungus, employs hydrolytic proteases for host invasion. Conventional antifungal agents are reported with resistance issues from around the world. This study investigates the role of Bacillus licheniformis extracellular proteins (ECP) as effective antifungal peptides (AFPs). The aim was to identify and characterize the ECP of B. licheniformis through LC-MS/MS and bioinformatics analysis. LC-MS/MS analysis identified 326 proteins with 69 putative ECP, further analyzed in silico. Of these, 21 peptides exhibited antifungal properties revealed by classAMP tool and are predominantly anionic. Peptide-protein docking revealed interactions between AFPs like Peptide chain release factor 1 (Q65DV1_Seq1: SASEQLSDAK) and Putative carboxy peptidase (Q65IF0_Seq7: SDSSLEDQDFILESK) with C. albicans virulent SAP5 proteins (PDB ID 2QZX), forming hydrogen bonds and significant Pi-Pi interactions. The identification of B. licheniformis ECP is the novelty of the study that sheds light on their antifungal potential. The identified AFPs, particularly those interacting with bonafide pharmaceutical targets SAP5 of C. albicans represent promising avenues for the development of antifungal treatments with AFPs that could be the pursuit of a novel therapeutic strategy against C. albicans. SIGNIFICANCE OF STUDY: The purpose of this work was to carry out proteomic profiling of the secretome of B. licheniformis. Previously, the efficacy of Bacillus licheniformis extracellular proteins against Candida albicans was investigated and documented in a recently communicated manuscript, showcasing the antifungal activity of these proteins. In order to achieve high-throughput identification of ES (Excretory-secretory) proteins, the utilization of liquid chromatography tandem mass spectrometry (LC-MS) was utilized. There was a lack of comprehensive research on AFPs in B. licheniformis, nevertheless. The proteins secreted by B. licheniformis in liquid medium were initially discovered using liquid chromatography-tandem mass spectrometry (LC-MS) analysis and identification in order to immediately characterize the unidentified active metabolites in fermentation broth.

Acetaminophen induces mitochondrial apoptosis through proteasome dysfunctions.

Acetaminophen is a known antipyretic and non-opioid analgesic for mild pain and fever. Numerous studies uncover their hidden chemotherapeutics applications, including chronic cancer pain management. Acetaminophen also represents an anti-proliferative effect in some cancer cells. Few studies also suggest that the use of Acetaminophen can trigger apoptosis and impede cellular growth. However, Acetaminophen's molecular potential and precise mechanism against improper cellular proliferation and use as an effective anti-proliferative agent still need to be better understood. Here, our current findings show that Acetaminophen induces proteasomal dysfunctions, resulting in aberrant protein accumulation and mitochondrial abnormalities, and consequently induces cell apoptosis. We observed that the Acetaminophen treatment leads to improper aggregation of ubiquitylated expanded polyglutamine proteins, which may be due to the dysfunctions of proteasome activities. Our in-silico analysis suggests the interaction of Acetaminophen and proteasome. Furthermore, we demonstrated the accumulation of proteasome substrates and the depletion of proteasome activities after treating Acetaminophen in cells. Acetaminophen induces proteasome dysfunctions and mitochondrial abnormalities, leading to pro-apoptotic morphological changes and apoptosis successively. These results suggest that Acetaminophen can induce cell death and may retain a promising anti-proliferative effect. These observations can open new possible molecular strategies in the near future for developing and designing specific and effective proteasome inhibitors, which can be helpful in conjugation with other anti-tumor drugs for their better efficiency.

Antimicrobial therapeutic protein extraction from fruit waste and recent trends in their utilization against infections.

Fruits are a very good source of various nutrients that can boost overall human health. In these days, the recovery of therapeutic compounds from different fruit wastes is trending in research, which might not only minimize the waste problem but also encounter a higher demand for various enzymes that could have antimicrobial properties against infectious diseases. The goal of this review is to focus on the recovery of therapeutic enzymes from fruit wastes and its present-day tendency for utilization. Here we discussed different parts of fruit waste, such as pulp, pomace, seed, kernel, peel, etc., that produce therapeutic enzymes like amylase, cellulose, lipase, laccase, pectinase, etc. These bioactive enzymes are present in different parts of fruit and could be used as therapeutics against various infectious diseases. This article provides a thorough knowledge compilation of therapeutic enzyme isolation from fruit waste on a single platform, distinctly informative, and significant review work on the topic that is envisioned to encourage further research ideas in these areas that are still under-explored. This paper explains the various aspects of enzyme isolation from fruit and vegetable waste and their biotherapeutic potential that could provide new insights into the development of biotherapeutics and attract the attention of researchers to enhance translational research magnitude further.

Synchronization of Mycobacterium life cycle: A possible novel mechanism of antimycobacterial drug resistance evolution and its manipulation.

Mycobacterium Tuberculosis (Mtb) causing Tuberculosis (TB) is a widespread disease infecting millions of people worldwide. Additionally, emergence of drug resistant tuberculosis is a major challenge and concern in high TB burden countries. Most of the drug resistance in mycobacteria is attributed to developing acquired resistance due to spontaneous mutations or intrinsic resistance mechanisms. In this review, we emphasize on the role of bacterial cell cycle synchronization as one of the intrinsic mechanisms used by the bacteria to cope with stress response and perhaps involved in evolution of its drug resistance. The importance of cell cycle synchronization and its function in drug resistance in cancer cells, malarial and viral pathogens is well understood, but its role in bacterial pathogens has yet to be established. From the extensive literature survey, we could collect information regarding how mycobacteria use synchronization to overcome the stress response. Additionally, it has been observed that most of the microbial pathogens including mycobacteria are responsive to drugs predominantly in their logarithmic phase, while they show resistance to antibiotics when they are in the lag or stationary phase. Therefore, we speculate that Mtb might use this novel strategy wherein they regulate their cell cycle upon antibiotic pressure such that they either enter in their low metabolic phase i.e., either the lag or stationary phase to overcome the antibiotic pressure and function as persister cells. Thus, we propose that manipulating the mycobacterial drug resistance could be possible by fine-tuning its cell cycle.

Molecular drilling to combat salmonella typhi biofilm using L-Asparaginase via multiple targeting process.

OBJECTIVES: Salmonella Typhibiofilm condition is showing as a major public health problem due to the development of antibiotic resistance and less available druggable target proteins. Therefore, we aimed to identify some more druggable targets of S. Typhibiofilm using computational drilling at the genome/proteome level so that the target shortage problem could be overcome and more antibiofilm agents could be designed in the future against the disease. METHODS: We performed protein-protein docking and interaction analysis between the homological identified target proteins of S.Typhi biofilm and a therapeutic protein L-Asparaginase. RESULTS: We have identified some druggable targets CsgD, BcsA, OmpR, CsgG, CsgE, and CsgF in S.Typhi. These targets showed high-binding affinity BcsA (-219.8 Kcal/mol) >csgF (-146.52 Kcal/mol) >ompR (-135.68 Kcal/mol) >CsgE (-134.66 Kcal/mol) >CsgG (-113.81 Kcal/mol) >CsgD(-95.39 Kcal/mol) with therapeutic enzyme L-Asparaginase through various hydrogen-bonds and salt-bridge. We found six proteins of S. Typhi biofilm from the Csg family as druggable multiple targets. CONCLUSION: This study provides insight into the idea of identification of new druggable targets and their multiple targeting with L-Asparaginase to overcome target shortage in S. Typhibiofilm-mediated infections. Results further indicated that L-Asparaginase could potentially be utilized as an antibiofilm biotherapeutic agent against S.Typhi.

Antidiabetic effectiveness of Phyllanthus niruri bioactive compounds via targeting DPP-IV.

Phyllanthus niruri Linn. (Euphorbiaceae) is a small herb and is categorised as one of the rich medicinal plants throughout the world. This study aimed to evaluate the P. niruri L. whole plant extract (PNE) for secondary metabolite assay (total phenolic and terpenoid content) followed by the potential antioxidant activity (ABTS diammonium salt radical assay, DPPH· activity, superoxide anion (O2-) radicals' assay, and nitric oxide (NO) radical generation) and antidiabetic activity in vivo and in vitro in streptozotocin (STZ) induced albino mice. PNE showed good scavenging activity with a value of 286.45 ± 6.55 mg TE/g and 194.54 ± 4.64 mg TE/g in ABTS and DPPH assays respectively. In the superoxide anion assay, the PNE caused a dose-dependent inhibition at the lowest IC25 value of 0.17 ± 0.00 mg/mL compared to ascorbic acid (IC25 of 0.25 ± 0.02 mg/mL). The scavenging ability of PNE against nitric oxide showed an IC25 of 1.13 ± 0.04 mg/mL compared to ascorbic acid (IC25 4.78 ± 0.09 mg/mL). Unlike diabetic control mice, the PNE-treated diabetic mice presented significant amelioration of glycaemia and lipid dysmetabolism. Phytochemicals like Astragalin, Gallocatechin, Ellagic acid, Gallic acid, Brevifolin carboxylic acid, Phyllnirurin, and Hypophyllanthin showed significant docking score (> -4) of inhibitory potential with DPP-IV protein. Results indicated that PNE phytochemicals could be a promising antidiabetic agent by targeting DPP-IV.

A Rare Entanglement: Self-Knotting of a Nasogastric Tube.

While nasogastric intubation is a commonplace procedure characterized by its utility in enteral feeding and gastrointestinal decompression, instances of unexpected complications are relatively infrequent. Herein, we describe an unusual and rare complication, knot formation, that surfaced during routine patient care. This unique case prompts a re-evaluation of the potential complications associated with nasogastric tube insertion and offers insights into the challenges faced in its management. Through this report, we aim to contribute to the understanding of rare complications in enteral feeding practices.

Modulators of Candida albicans Membrane Drug Transporters: A Lucrative Portfolio for the Development of Effective Antifungals.

The escalating prevalence of membrane drug transporters and drug efflux pumps in pathogenic yeast like Candida albicans necessitates a comprehensive understanding of their roles in MDR. The overexpression of drug transporter families, ABC and MFS, implicated in MDR through drug efflux and poses a significant challenge in the diagnosis and treatment of fungal infection. Various mechanisms have been proposed for MDR; however, the upregulation of ABC and MFS superfamily transporters is most noticeable in MDR. The direct inhibition of these transporters seems an efficient strategy to overcome this problem. The goal of the article is to present an overview of the prospect of utilizing these modulators of C. albicans drug transports as effective antifungal molecules against MDR addressing a critical gap in the field. The review tries to address to prevent drug extrusion by modulating the expression of drug transporters of C. albicans. The review discussed the progress in identifying potent, selective, and non-toxic modulators of these transporters to develop some effective antifungals and overcome MDR. We reviewed major studies in this area and found that recent work has shifted toward the exploration of natural compounds as potential modulators to restore drug sensitivity in MDR fungal cells. The focus of this review is to survey and interpret current research information on modulators of C. albicans drug transporters from natural sources emphasizing those compounds that are potent antifungal agents.

Interrogating Salmonella Typhi biofilm formation and dynamics to understand antimicrobial resistance.

AIMS: Salmonella Typhi biofilm-mediated infections are globally rising. Due to the emergence of drug resistance antibiotics did not show effective results against S. Typhi biofilm. Therefore, there is an urgent need for an in-depth interrogation of S. Typhi biofilm to understand its formation kinetics, compositions, and surface charge value. METHODS: This study utilized the S. Typhi MTCC-733 strain from a microbial-type culture collection in India. The S. Typhi biofilm was formed on a glass slide in a biofilm development apparatus. Typhoidal biofilm analysis was done with the help of various assays such as a crystal violet assay, SEM analysis, FTIR analysis, Raman analysis, and zeta potential analysis. KEY FINDING: This article contained a comprehensive assessment of the typhoid biofilm formation kinetics, biofilm compositions, and surface charge which revealed that cellulose was a major molecule in the typhoidal biofilm which can be used as a major biofilm drug target against typhoidal biofilm. SIGNIFICANCE: This study provided interrogations about typhoidal biofilm kinetics which provided ideas about the biofilm composition. The cellulose molecule showed a major component of S. Typhi biofilm and it could potentially involved in drug resistance, and offer a promising avenue for developing a new antibiofilm therapeutic target to conquer the big obstacle of drug resistance. The obtained information can be instrumental in designing novel therapeutic molecules in the future to combat typhoidal biofilm conditions effectively for overcoming antibiotic resistance against bacterial infection Salmonella.

Candida die-off: Adverse effect and neutralization with phytotherapy approaches.

Candida albicans is the main species that causes 3rd most common bloodstream infection candidiasis in hospitalization. Once it has been diagnosed and treated with antifungal medications accurately, large amounts of Candida cells are killed off rapidly known as Candida die-off or Jarisch-Herxheimer reactions. When Candida cells are killed off quickly, a large no. of toxic substances are released simultaneously. This flood of endotoxins is noxious (harmful) and causes the kidneys and liver to work overtime to try and remove them which causes worsening of symptoms in patients. As a complementary and holistic approach to addressing Candida die-off and its associated symptoms, plant-based remedies i.e., phytotherapy have been gaining increased attention. In this review paper, we have discussed major factors involved in provoking Candida die-off, their management by phytotherapy, challenges associated with the toxic effects due to die-off, and neutralization of Candida die-off through phytotherapy to manage this problem and challenges. In conclusion, this article serves as a meticulous compilation of knowledge on the intriguing subject of Candida die-off, presenting a distinct and informative perspective that has the potential to pave the way for new insights in the realm of plant-based antifungal therapeutics.