The evolving facets of vaginal microbiota transplantation: reinvigorating the unexplored frontier amid complex challenges.

In an age of cutting-edge sequencing methods and worldwide endeavors such as The Human Microbiome Project and MetaHIT, the human microbiome stands as a complex and diverse community of microorganisms. A central theme in current scientific inquiry revolves around reinstating a balanced microbial composition, referred to as "eubiosis," as a targeted approach for treating vast array of diseases. Vaginal Microbiota Transplantation (VMT), inspired by the success of fecal microbiota transplantation, emerges as an innovative therapy addressing vaginal dysbacteriosis by transferring the complete microbiota from a healthy donor. Antibiotics, while effective, pose challenges with adverse effects, high recurrence rates, and potential harm to beneficial Lactobacillus strains. Continued antibiotic usage also sparks worries regarding the development of resistant strains. Probiotics, though showing promise, exhibit inconsistency in treating multifactorial diseases, and concerns linger about their suitability for diverse genetic backgrounds. Given the recurrent challenges associated with antibiotic and probiotic treatments, VMT emerges as an imperative alternative, offering a unique and promising avenue for efficiently and reliably managing vaginal dysbiosis among a majority of women. This review critically evaluates findings from both animal and human studies, offering nuanced insights into the efficacy and challenges of VMT. An extensive analysis of clinical trials, provides a current overview of ongoing and completed trials, shedding light on the evolving clinical landscape and therapeutic potential of VMT. Delving into the origins, mechanisms, and optimized protocols of VMT, the review underscores the imperative for sustained research efforts to advance this groundbreaking gynecological therapy.

Quantum dots: a next generation approach for pathogenic microbial biofilm inhibition; mechanistic insights, existing challenges, and future potential.

Quantum Dots (QDs) have emerged as versatile nanomaterials with origins spanning organic, inorganic, and natural sources, revolutionizing various biomedical applications, particularly in combating pathogenic biofilm formation. Biofilms, complex structures formed by microbial communities enveloped in exopolysaccharide matrices, pose formidable challenges to traditional antibiotics due to their high tolerance and resistance, exacerbating inefficacy issues in antibiotic treatments. QDs offer a promising solution, employing physical mechanisms like photothermal or photodynamic therapy to disrupt biofilms. Their efficacy is noteworthy, with lower susceptibility to resistance development and broad-spectrum action as compared to conventional antibiotic methods. The stability and durability of QDs ensure sustained biofilm activity, even in challenging environmental conditions. This comprehensive review delves into the synthesis, properties, and applications of Carbon Quantum Dots (CQDs), most widely used QDs, showcasing groundbreaking developments that position these nanomaterials at the forefront of cutting-edge research and innovation. These nanomaterials exhibit multifaceted mechanisms, disrupting cell walls and membranes, generating reactive oxygen species (ROS), and binding to nucleic materials, effectively inhibiting microbial proliferation. This opens transformative possibilities for healthcare interventions by providing insights into biofilm dynamics. However, challenges in size control necessitate ongoing research to refine fabrication techniques, ensure defect-free surfaces, and optimize biological activity. QDs emerge as microscopic yet potent tools, promising to contribute to a brighter future where quantum wonders shape innovative solutions to persistently challenging issues posed by pathogenic biofilms. Henceforth, this review aims to explore QDs as potential agents for inhibiting pathogenic microbial biofilms, elucidating the underlying mechanisms, addressing the current challenges, and highlighting their promising future potential.

Deciphering the potential of proteomic-based biomarkers in women's reproductive diseases: empowering precision medicine in gynecology.

CONTEXT: Gynecological disorders represent a complex set of malignancies that result from a diverse array of molecular changes affecting the lives of over a million women worldwide. Ovarian, Endometrial, and Cervical cancers, Endometriosis, PCOS are the most prevalent ones that pose a grave threat to women's health. Proteomics has emerged as an invaluable tool for developing novel biomarkers, screening methods, and targeted therapeutic agents for gynecological disorders. Some of these biomarkers have been approved by the FDA, but regrettably, they have a constrained diagnostic accuracy in early-stage diagnosis as all of these biomarkers lack sensitivity and specificity. Lately, high-throughput proteomics technologies have made significant strides, allowing for identification of potential biomarkers with improved sensitivity and specificity. However, limited successes have been shown with translation of these discoveries into clinical practice. OBJECTIVE: This review aims to provide a comprehensive overview of the current and potential protein biomarkers for gynecological cancers, endometriosis and PCOS, discusses recent advances and challenges, and highlights future directions for the field. CONCLUSION: We propose that proteomics holds great promise as a powerful tool to revolutionize the fight against female reproductive diseases and can ultimately improve personalized patient outcomes in women's biomedicine.

Horizons of nanotechnology applications in female specific cancers.

Female-specific cancers are the most common cancers in women worldwide. Early detection methods remain unavailable for most of these cancers, signifying that most of them are diagnosed at later stages. Furthermore, current treatment options for most female-specific cancers are surgery, radiation and chemotherapy. Although important milestones in molecularly targeted approaches have been achieved lately, current therapeutic strategies for female-specific cancers remain limited, ineffective and plagued by the emergence of chemoresistance, which aggravates prognosis. Recently, the application of nanotechnology to the medical field has allowed the development of novel nano-based approaches for the management and treatment of cancers, including female-specific cancers. These approaches promise to improve patient survival rates by reducing side effects, enabling selective delivery of drugs to tumor tissues and enhancing the uptake of therapeutic compounds, thus increasing anti-tumor activity. In this review, we focus on the application of nano-based technologies to the design of novel and innovative diagnostic and therapeutic strategies in the context of female-specific cancers, highlighting their potential uses and limitations.

A literature review on correlation between HPV coinfection with C. trachomatis and cervical neoplasia - coinfection mediated cellular transformation.

Cervical cancer is the fourth most common cause of mortality worldwide. Persistent infection with high-risk human papillomaviruses (hrHPV) is a known significant risk factor in cervical neoplasia development (CN). Though HPV contributes to carcinogenesis, other factors provide an ideal niche for persistence of HPV, especially, coinfection with Chlamydia trachomatis (CT) which has been linked to CN development. CT infection is associated with inflammation, cell proliferation, EMT transition and anti-apoptotic processes. To better understand the correlation between HPV-CT coinfection and CN development, a literature review was conducted on the prevalence of HPV-CT coinfection focusing on the role of infection-induced inflammation as HPV-CT coinfection creates an environment for cellular transformation, activates an innate immune response and triggers EMT transition. Moreover, inflammation plays a crucial role in developing neoplasia as there is a decrease in effector cells and a change in the levels of players like ROS and miRs. CT infection induces chronic inflammation followed by cervical epithelial cell damage and increases susceptibility to HPV infection which may lead to cellular transformation. The literature search was performed based on a comprehensive investigation of publications in the PubMed journal database and Scopus, on the development of CN. We have reviewed the prevalence of HPV-CT infection and the factors increasing the risk of developing CN.

Association of cervicovaginal dysbiosis mediated HPV infection with cervical intraepithelial neoplasia.

Cellular transformation to malignancy is a multifactorial process strongly linked with microbiome dysbiosis. The female reproductive tract (FRT) is inhabited by specific Lactobacillus spp which play a significant role in maintaining a homeostatic balance and providing resistance to perturbation. Any imbalance in the resident microbiota of the FRT results in cervicovaginal dysbiosis and increased predisposition to viral and bacterial infections. In the present review, we discuss the critical role played by the cervicovaginal microbiome in maintaining cervicovaginal homeostasis. Loss of the mutualistic relationship between cervicovaginal microbiota and the host leads to increased susceptibility to Human papilloma virus (HPV) infection. HPV in coinfection with Chlamydia trachomatis has been linked with increased risk for cellular transformation. The progression to cervical neoplasia is a multistep process regulated by cellular and epigenetic changes mediated by oncogenes and miRNA. Exosomes derived from the infected cells play an important role in the pathological development and progression to cervical neoplasia as they harbor the regulatory molecules like miRNA, proteins and prooncogenic factors which may facilitate cellular transformation.

Recent advances in metabolomics of triple negative breast cancer.

Triple-negative Breast Cancer (TNBC) is considered as the most aggressive subtype of breast cancer. Metabolic profiling has a great significance in cancer research due to profound changes in the metabolism of cancer cells. It has been used to investigate the entire set of metabolites and changes associated with it in disease conditions. These changes in the expression levels of metabolites bring functional changes associated with the pharmacological or nutritional intervention. The present minireview presents a brief note on changes associated with TNBC aggressiveness in terms of metabolomics.

Synergistic enhancement of apoptosis by coralyne and paclitaxel in combination on MDA-MB-231 a triple-negative breast cancer cell line.

Triple-negative breast cancer (TNBC) is the most outrageous subtype of breast cancer. Emphasizing the urge of new approach in cancer therapy, combinational drug therapy may be proven as an effective strategy. In our previous study, we reported that coralyne (COR) with paclitaxel (PTX) efficiently decreases the proliferation of MDA-MB-231 compared with MCF-7 cell line. Thus, we studied the effect of COR and PTX in combination on apoptosis of MDA-MB-231 cell line. In silico results demonstrated that COR intercalates DNA at a minor groove. In vitro approaches revealed that in combination (COR and PTX) increases the efficacy of apoptosis in MDA-MB-231 cell line by a significant increase in G1/S phase arrest, DNA fragmentation, and change in mitochondria membrane potential. The expression of ATM and ATR a serine/threonine-protein kinase, ataxia telangiectasia and Rad3-related protein were depleted with an increase in time from 24 to 48 hours in concurrent with increased levels of γH2AX indicating that DNA damage routes cells to enter apoptosis. This was confirmed by high levels of caspase-3 and cytochrome c. Also, the decrease in the expression levels of matrix metalloproteinase-9 confirmed the antimetastatic efficacy of COR + PTX. The present study indicates that the synergistic effect of COR and PTX can enhance apoptosis in MDA-MB-231 cell line and may be proven as a potential anticancer therapy against TNBC.

Synthesis, biological evaluation and molecular docking study of 1-amino-2-aroylnaphthalenes against prostate cancer.

A series of functionalized naphthalene was synthesized and screened against human prostate cancer cell line (PC-3). The in vitro antiproliferative activity of the synthesized compounds was evaluated by monitoring their cytotoxic effects against PC-3 cells by using MTT assay. We observed that compound 5f resulted in more than 50% cell death at 14 µM. Treatment of PC-3 cells with 5f provides apoptosis by flow cytometry. Western blotting showed decreased expression of pro-caspase 8 and 9. Our study shows that cancer cell treated with 5f has higher concentration of reactive oxygen species as compare to untreated sample, which facilitate cancerous cell to enter apoptosis. Exact mechanism by which ROS is generated after 5f treatment is still under study. Molecular docking study further strengthens the results obtained from in vitro experiments. Compound 5f can be considered as a promising leads for anticancer agent against prostate cancer cells due to its potent cytotoxic activity and apoptotic effect.

C-glycosyl flavone from Urginea indica inhibits proliferation & angiogenesis & induces apoptosis via cyclin-dependent kinase 6 in human breast, hepatic & colon cancer cell lines.

BACKGROUND & OBJECTIVES: Search for novel compounds beneficial to the treatment of cancer attracts a great deal of attention. We earlier demonstrated the isolation of 5,7-dihydroxy-2-[4'-hydroxy-3'-(methoxymethyl)phenyl]-6-C-ß-glucopyranosyl flavone, a novel C-glycosyl flavone from Urginea indica bulb. The present study was undertaken to investigate the effect of this novel compound on human normal epithelial and breast, hepatic and colon cancer cell lines. METHODS: : The maximum non-toxic concentration (MNTC) and cytotoxicity of C-glycosyl flavone were assayed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). Cell cycle was analyzed by flow cytometry. Docking studies were performed to predict possible targets. Levels of cyclin-dependent kinase 1 (CDK1) and CDK6, Bcl2 and BAX and cytochrome c were quantified by specific ELISA. Mitochondrial membrane potential was determined using JC-1 dye. Apoptosis was quantified by Annexin V ELISA method. RESULTS: : Flow cytometry analysis demonstrated G0/G1 arrest. In silico docking studies predicted CDK1 and CDK6 as a possible target of C-glycosyl flavone. In vitro study confirmed CDK6 as the main target in C-glycosyl flavone-treated cancer cell lines. C-glycosyl flavone treatment also induced membrane blebbing, chromatin fragmentation and nucleosome formation. C-glycosyl flavone treatment caused marked loss of mitochondrial membrane potential, decrease in Bcl2/BAX ratio and activation of caspase-3 and release of caspase-9 and cytochrome c. In addition, C-glycosyl flavone inhibited the tumour-induced angiogenesis and reduced the vascular endothelial growth factor levels. Similarly, CDK6 inhibitor significantly inhibited proliferation and angiogenesis and induced apoptosis in tested cell lines. INTERPRETATION & CONCLUSIONS: The results indicate that C-glycosyl flavone may exert induction of apoptosis, cell cycle arrest and inhibition of angiogenesis via CDK6. Thus, targeting CDK6 using C-glycosyl flavone may serve as a novel therapeutic approach for the treatment of breast, hepatic and colon cancers.

Insecticidal effect of plant extracts on Phlebotomus argentipes (Diptera: Psychodidae) in Bihar, India.

BACKGROUND & OBJECTIVES: Phlebotomus argentipes (Diptera: Psychodidae), the established vector for kala-azar is presently being controlled by indoor residual spray of DDT in kala-azar endemic areas in India. Search for non-hazardous and non-toxic biodegradable active molecules from botanicals may provide cost-effective and eco-friendly alternatives to synthetic insecticides. The present study was aimed at evaluating various plant extracts from endemic and non-endemic areas of Bihar for their insecticidal activity against sandfly to identify the most effective plant extract. METHODS: Bio-assay test was conducted with larvae and adult of P. argentipes with different plant extracts collected in distilled water, hexane, ethyl acetate, acetone and methanol. Thin layer chromatography (TLC), column chromatography and high performance liquid chromatography (HPLC) were conducted for detection of active molecules. RESULTS: Adults and larvae of sandflies exposed to the aqueous extract of Nicotiana tabacum resulted in 100 per cent mortality. The hexane extract of Clerodendrum infortunatum was found to kill 77 per cent adults but was ineffective against larvae. Bio-assay test of the ninth fraction (hexane extract-methanol phase) separated by column chromatography was found to be 63 per cent effective. The purple spot on the TLC of this fraction indicated the presence of a diterpenoid. HPLC of this fraction detected nine compounds with two peaks covering 20.44 and 56.52 per cent areas with retention time of 2.439 and 5.182 min, respectively supporting the TLC results. INTERPRETATION & CONCLUSIONS: The column separated 9 [th] fraction of C. infortunatum extract was found to be effective in killing 63 per cent of adult P. argentipes. Compounds of this fraction need to be evaluated further for identification and characterization of the active molecule by conducting individual bio-assay tests followed by further fractionation and HPLC. Once the structure of the active molecule is identified and validated, it may be synthesized and formulated as a product.

The potentiality of botanicals and their products as an alternative to chemical insecticides to sandflies (Diptera: Psychodidae): a review.

Use of chemical pesticides is the current method for controlling sandflies. However, resistance is being developed in sandflies against the insecticide of choice that is DDT (dichlorodiphenyl trichloroethane). Botanicals have potential to act as an alternative to chemical insecticides as the crude extracts and active molecules of some plants show insecticidal effect to sandflies. This will lead to safe, easy and environment friendly method for control of sandflies. Therefore, information regarding botanicals acting as alternative to chemical insecticide against sandflies assumes importance in the context of development of resistance to insecticides as well as to prevent environment from contamination. This review deals with some plants and their products having repellent and insecticidal effect to sandflies in India and abroad. Different methods of extraction and their bioassay on sandflies have been emphasized in the text. Various extracts of some plants like Ricinus communis (Euphorbiaceae), Solanum jasminoides (Solanaceae), Bougainvillea glabra (Nyctaginaceae), Capparis spinosa (Capparidaceae), Acalypha fruticosa (Euphorbiaceae) and Tagetes minuta (Asteraceae) had shown repellent/insecticidal effect on sandflies. This review will be useful in conducting the research work to find out botanicals of Indian context having insecticidal effect on sandflies.

Treatment patterns and long-term survival outcomes for patients with stage III non-small cell lung cancer: A retrospective study.

AIM: Lung cancer is the leading cause of cancer-related deaths in Australia with poor long-term survival outcomes. Stage III non-small cell lung cancer (NSCLC) is a highly heterogenous group with diverse tumor characteristics and multiple, possible treatment options. We present retrospective data on patient characteristics, treatment patterns, and long-term outcomes in stage III NSCLC patients treated at a single cancer center in New South Wales, Australia. METHODS: Stage III NSCLC patients were identified from the 'Nepean Cancer Research Biobank'. Patient demographics, cancer-related information, and long-term follow-up data were collected and analyzed. RESULTS: A total of 88 patients were eligible for analysis with 61% of them diagnosed as stage IIIA, 35% IIIB, and 4% IIIC. Induction chemotherapy was administered in 20% of the patients. Overall, 48% of the study population underwent surgery, and 38% underwent concurrent chemoradiotherapy (CCRT). Both median progression-free survival and overall survival (OS) were superior in stage IIIA patients in comparison to stage IIIB (and IIIC) patients (22 vs. 11 months, p = .018; and 58 vs. 19 months, p = .048, respectively). Patients who were younger (<65 years old), good Eastern Cooperative Oncology Group performance status (ECOG PS <2), and females had better prognosis on univariate analysis. There was a nonstatistically significant trend toward better median OS with CCRT in comparison to surgery (58 vs. 37 months, p = .87). CONCLUSIONS: Long-term outcomes remain poor, and hence better treatment strategies are urgently needed in stage III NSCLC. Equally, more robust, prospective studies would help delineate the optimal treatment modality in these patients.

Small molecular inhibitors: Therapeutic strategies for pancreatic cancer.

Pancreatic cancer (PC), a disease with high heterogeneity and a dense stromal microenvironment, presents significant challenges and a bleak prognosis. Recent breakthroughs have illuminated the crucial interplay among RAS, epidermal growth factor receptor (EGFR), and hedgehog pathways in PC progression. Small molecular inhibitors have emerged as a potential solution with their advantages of oral administration and the ability to target intracellular and extracellular sites effectively. However, despite the US FDA approving over 100 small-molecule targeted antitumor drugs, challenges such as low response rates and drug resistance persist. This review delves into the possibility of using small molecules to treat persistent or spreading PC, highlighting the challenges and the urgent need for a diverse selection of inhibitors to develop more effective treatment strategies.

Antimicrobial and Antibiofilm Potential of Green-Synthesized Graphene-Silver Nanocomposite against Multidrug-Resistant Nosocomial Pathogens.

Hospital-acquired infections (HAIs) pose a significant risk to global health, impacting millions of individuals globally. These infections have increased rates of morbidity and mortality due to the prevalence of widespread antimicrobial resistance (AMR). Graphene-based nanoparticles (GBNs) are known to possess extensive antimicrobial properties by inflicting damage to the cell membrane, suppressing virulence, and inhibiting microbial biofilms. Developing alternative therapies for HAIs and addressing AMR can be made easier and more affordable by combining nanoparticles with medicinal plants harboring antimicrobial properties. Hence, this study was undertaken to develop a novel graphene-silver nanocomposite via green synthesis using Trillium govanianum plant extract as a reducing agent. The resulting nanocomposite comprised silver nanoparticles embedded in graphene sheets. The antibacterial and antifungal properties of graphene-silver nanocomposites were investigated against several nosocomial pathogens, namely, Candida auris, Candida glabrata, Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, and Pseudomonas aeruginosa. The nanocomposite displayed broad-range antimicrobial potential against the test pathogens, with minimum inhibitory concentrations (MICs) ranging between 31.25 and 125.0 µg/mL, and biofilm inhibition up to 80-96%. Moreover, nanocomposite-functionalized urinary catheters demonstrated hemocompatibility towards sheep erythrocytes and imparted anti-fouling activity to the biomaterial, while also displaying biocompatibility towards HEK 293 cells. Collectively, this investigation highlights the possible application of green-synthesized GBNs as an effective alternative to conventional antibiotics for combating multidrug-resistant pathogens.

Removal of organic and inorganic effluents from wastewater by using degradation and adsorption properties of transition metal-doped nickel ferrite.

Removal of water pollutants (methylene blue dye and heavy metals) was achieved by zinc/manganese-doped nickel ferrites (Ni1 - xMxFe2O4, where x = 0.00, 0.025, 0.10). Degradation of dye was achieved under natural solar light illumination. Degradation studies of dye were conducted under different parameters such as contact time-80 min, dye's concentration-5 mg/L, pH-7, and dosage of ferrites-15 mg. The adsorption of dye was studied using non-linear kinetics models (pseudo-first-order and pseudo-second-order) and isotherm models (Langmuir and Freundlich). The adsorption of dye followed pseudo-first-order kinetics (R2 = 0.99377) than second-order kinetics (R2 = 0.98063) and Langmuir isotherm model (R2 = 0.96095) than Freundlich model (R2 = 0.95962) with maximum adsorption efficiency of 29.62 mg/g. Doping of nickel ferrites caused an increase in the removal percentage of methylene blue dye (80 to 90%) and inorganic effluents (75 to 95% for lead and 47 to 82% for cadmium). In addition to this, band gap energy (2.43 to 3.26 eV) (UV-Vis spectroscopy), pore radius (65.2 to 74.8 A°), and specific surface area (16.45 to 27.95 m2/g) (BET analysis) were also increased. Generally, the results of the study revealed that synthesized nanoparticles can act as potential candidate for the removal of effluents from wastewater under optimum parameters along with recyclability, reusability, and separation under the influence of a magnetic field.

An experimental study to decipher the implications of antigenic sharing between Proteus mirabilis and mouse spermatozoa in eliciting an antisperm immune response: A potential culprit in immune infertility.

The present study aims to investigate the antigenic cross reactivity between the receptor from Proteus mirabilis and spermatozoa against a common sperm immobilization factor, SIF, by calorimetric and competitive inhibition studies, and the immunogenicity of this receptor to evoke the formation of antisperm antibodies and their subsequent role in fertility outcome. The sperm binding receptor from Proteus mirabilis (PM-SBR) was extracted from ultrasonicated cell debris by treating it for 12 h at 37°C with 1 M NaCl. After being purified by gel permeation chromatography, its molecular weight as determined by SDS-PAGE was observed to be ≈ 47 kDa. The detrimental impacts of Sperm immobilizing factor (SIF) on spermatozoa viz. motility, viability, and morphology were mitigated when SIF was preincubated with various concentrations of PM-SBR. Using isothermal titration calorimetry, the entropy of the SIF-PM-SBR interaction was found to be -18.31 kJ/mol, whereas the free energy was 28.4 J/mol K. FTIR analysis was used to evaluate the binding interactions between PM-SBR and SIF. In addition, mice that were administered antibodies against PM-SBR were unable to conceive, in contrast to mice that were administered Phosphate buffer saline (PBS) or pre-immunization serum as controls. In light of this, we may conclude that anti-PM-SBR antibodies act as anti-sperm antibodies. Our work found that molecular mimicry between Proteus mirabilis and spermatozoa may cause antisperm immune reactivity. As a result of an immunological response to PM-SBR, infected individuals may produce antibodies against an epitope similar to one found on spermatozoa which helps in developing new strategies for managing autoimmune responses and infertility.

Enhancing wheat crop production with eco-friendly chitosan encapsulated nickel oxide nanocomposites: A safe and sustainable solution for higher yield.

In this work, we looked at using nickel oxide (NiO) nanocomposites with chitosan encapsulation as a nano-primer to improve wheat crop output. A straightforward green precipitation procedure was used to create the nanocomposites, and they were then characterized using several methods. According to the findings, the chitosan-encapsulated NiO nanocomposites possessed a large surface area and were resilient to changes in pH. Following this, wheat seeds were primed with the nanocomposites, and under greenhouse circumstances, the impact on crop growth was assessed. The findings demonstrated that, in comparison to the control group, nanocomposites priming considerably enhanced wheat growth and germination rate up to 99 %. In comparison to untreated plants, the wheat plants treated with the nanocomposites primer had greater plant height i.e. shoot length (11.4 cm) and root length (10.3 cm), leaf area, and biomass accumulation. Further research into the mechanism underlying the priming effect of nanocomposites on wheat growth revealed that the nanocomposites enhanced nutrient absorption, photosynthesis, and stress tolerance in wheat plants. In conclusion, our research shows that chitosan-encapsulated NiO nanocomposites have the potential to improve wheat crop productivity in an environmentally benign and long-term manner, offering a viable strategy for sustainable farming.

Levofloxacin loaded clove oil nanoscale emulgel promotes wound healing in Pseudomonas aeruginosa biofilm infected burn wound in mice.

Owing to their tolerance to antibiotics, bacterial biofilms continue to pose a threat to mankind and are leading cause for non-healing of burn wounds. Within the biofilm matrix, antibiotics become functionally inactive due to restricted penetration and enzymatic degradation leading to rise of antimicrobial resistance. The objective of present investigation was to develop and characterize levofloxacin (LFX) loaded clove oil nanoscale emulgel (LFX-NE gel) and evaluate its in vivo therapeutic efficacy in Pseudomonas aeruginosa biofilm infected burn wound in mice. The optimized emulgel was found to possess good texture profile and showed shear thinning behavior. In vitro release study demonstrated complete drug release in 8 h and emulgel was found to be stable for 3 months at 25 °C and 40 °C. In vivo study revealed biofilm dispersal, complete wound closure, re-epithelialization and collagen deposition by LFX-NE gel in comparison to various control groups. LFX-NE gel was able to clear the infection within 7 days of treatment and promote wound healing as well. Therefore, administration of LFX-incorporated NE gel could be a beneficial treatment strategy for P. aeruginosa biofilm-infected burn wounds.

Microbiome Assisted Tumor Microenvironment: Emerging Target of Breast Cancer.

The microbiome assisted tumor microenvironment (TME) supports the tumors by modulating multiple mechanisms. Recent studies reported that microbiome dysbiosis is the main culprit of immune suppressive phenotypes of TME. Further, it has been documented that immune suppressive stimulate metastatic phenotype in TME via modulating signaling pathways, cell differentiation, and innate immune response. This review aims at providing comprehensive developments in microbiome and breast TME interface. The combination of microbiome and breast cancer, breast TME and microbiome or microbial dysbiosis, microbiome and risk of breast cancer, microbiome and phytochemicals or anticancer drugs were as used keywords to retrieve literature from PubMed, Google scholar, Scopus, Web of Science from 2015 onwards. Based on the literature, we presented the impact of TME assisted microbiome dysbiosis and estrobolome in breast cancer risk, drug resistance, and antitumor immunity. We have discussed the influence of antibiotics on the breast microbiome. we also presented the possible dietary phytochemicals that target microbiome dysbiosis to restore the tumor suppression immune environment in breast TME. We presented the microbiome as a possible marker for breast cancer diagnosis. This study will help in the identification of microbiome as a novel target and diagnostic markers and phytochemicals and microbiome metabolites for breast cancer treatment.