Identification of novel biomarkers and potential molecular targets for uterine cancer using network-based approach.

A better understanding of incidences at the cellular level in uterine cancer is necessary for its effective treatment and favourable prognosis. Till date, it lacks appropriate molecular target-based treatment because of unknown molecular mechanisms that proceed to cancer and no drug has shown the required results of treatment with less severe side effects. Uterine Cancer is one of the top five cancer diagnoses and among the ten most common death-causing cancer in the United States of America. There is no FDA-approved drug for it yet. Therefore, it became necessary to identify the molecular targets for molecular targeted therapy of this widely prevalent cancer type. For this study, we used a network-based approach to the list of the deregulated (both up and down-regulated) genes taking adjacent p-Value ≤ 0.05 as significance cut off for the mRNA data of uterine cancer. We constructed the protein-protein interaction (PPI) network and analyzed the degree, closeness, and betweenness centrality-like topological properties of the PPI network. Then we traced the top 30 genes listed from each topological property to find the key regulators involved in the endometrial cancer (ECa) network. We then detected the communities and sub-communities from the PPI network using the Cytoscape network analyzer and Louvain modularity optimization method. A set of 26 (TOP2A, CENPE, RAD51, BUB1, BUB1B, KIF2C, KIF23, KIF11, KIF20A, ASPM, AURKA, AURKB, PLK1, CDC20, CDKN2A, EZH2, CCNA2, CCNB1, CDK1, FGF2, PRKCA, PGR, CAMK2A, HPGDS, and CDCA8) genes were found to be key genes of ECa regulatory network altered in disease state and might be playing the regulatory role in complex ECa network. Our study suggests that among these genes, KIF11 and H PGDS appeared to be novel key genes identified in our research. We also identified these key genes interactions with miRNAs.

Concurrent chemoradiation with low-dose and long-duration weekly infusion of gemcitabine in unresectable squamous cell carcinoma of head and neck (SCCHN).

BACKGROUND: Concurrent chemoradiotherapy now represents the standard of care in locally advanced unresectable squamous cell carcinoma of the head and neck, and the administration of cisplatin in triweekly or weekly schedules is the most commonly used chemotherapeutic agent. However, the chemotherapeutic agent and its scheduling with radiation is still an area of investigation with safer toxicity profile and better response rates. Gemcitabine is a potent radiosensitizer, and non-cytotoxic concentration results in decreased systemic toxicity while maintaining radiosensitization properties. Furthermore, data are emerging for low-dose and long-duration infusion where this strategy is found to be effective and a safe alternative to standard brief infusion. Based on these two strategies, that is, non-cytotoxic concentration with long duration, we have explored the unique possibility of further lowering the toxicity profile without compromising the efficacy. METHOD: Eligible patients of locally advanced unresectable squamous cell carcinoma of the head and neck underwent radiation treatment with concurrent gemcitabine. A total dose of 70 Gy in 35 fractions over a period of seven weeks with conventional fractionation schedule was delivered with cord off after 44 Gy. Concurrent gemcitabine was administered intravenously for over two hours once a week, 1-2 h before radiation and for seven consecutive weeks at 50 mg/m2. RESULT: Fifty-two patients was enrolled in this study, out of which 41 completed the treatment. Fifty-nine percent completed treatment within seven weeks. Sixty-four percent were found to have received more than five cycles. Mean follow-up of patients was found to be 4.9 months. Sixty-eight percent had complete response. Stage III patients achieved more complete response compared to stage IV. There was no site-wise difference in achieving complete response. Patients who have received less than five chemo cycles or completed the treatment in more than seven weeks had less complete response. Sixty-one percent had severe mucositis while 39% developed mild/moderate mucositis. Considering skin toxicity, 80% were found to have mild/moderate skin toxicity, while only 20% suffered from severe grades of skin toxicity. CONCLUSION: Gemcitabine in low-dose and long-duration infusion is a potent radiosensitizer with safer hematological toxicity and manageable local toxicities.

New opportunities for antioxidants in amelioration of neurodegenerative diseases.

This comprehensive review elucidates the critical role of antioxidants to mitigate oxidative stress, a common denominator in an array of neurodegenerative disorders. Oxidative stress-induced damage has been linked to the development of diseases such as Alzheimer's, Parkinson's, Huntington's disease and amyotrophic lateral sclerosis. This article examines a wide range of scientific literature and methodically delineates the several methods by which antioxidants exercise their neuroprotective benefits. It also explores into the complex relationship between oxidative stress and neuroinflammation, focusing on how antioxidants can alter signaling pathways and transcription factors to slow neurodegenerative processes. Key antioxidants, such as vitamins C and E, glutathione, and polyphenolic compounds, are tested for their ability to combat reactive oxygen and nitrogen species. The dual character of antioxidants, which operate as both direct free radical scavengers and regulators of cellular redox homeostasis, is investigated in terms of therapeutic potential. Furthermore, the study focuses on new antioxidant-based therapy techniques and their mechanisms including Nrf-2, PCG1α, Thioredoxin etc., which range from dietary interventions to targeted antioxidant molecules. Insights into ongoing clinical studies evaluating antioxidant therapies in neurodegenerative illnesses offer an insight into the translational potential of antioxidant research. Finally, this review summarizes our present understanding of antioxidant processes in neurodegenerative illnesses, providing important possibilities for future study and treatment development.

Comparative study on efficiency of surface enhanced coal fly ash and raw coal fly ash for the removal of hazardous dyes in wastewater: optimization through response surface methodology.

Crystal violet (CV) dye, because of its non-biodegradability and harmful effects, poses a significant challenge for wastewater treatment. This study addresses the efficiency of easily accessible coal fly ash (CFA)-based adsorbents such as raw coal fly ash (RCFA) and surface enhanced coal fly ash (SECFA), in removing CV dye from waste effluents. Various analytical techniques such as FTIR, XRD, SEM, TEM, BET, zeta sizer and zeta potential were employed for the characterization of the adsorbents and dye-loaded samples. BET revealed that RCFA possesses a surface area of 19.370 m2 g-1 and SECFA of 27.391 m2 g-1, exhibiting pore volumes of 0.1365 cm3 g-1 and 0.1919 cm3 g-1 respectively. Zeta-sizer and potential analysis showed the static charges of RCFA as -27.3 mV and SECFA as -28.2 mV, with average particle sizes of 346.6 and 315.3 nm, respectively. Langmuir and Freundlich adsorption isotherms were also employed for adsorption studies. Employing central composite design (CCD) of response surface methodology (RSM), the maximum CV removal was 81.52% for RCFA and 97.52% for SECFA, providing one minute contact time, 0.0125 g adsorbent dose and 10 ppm dye concentration. From the thermodynamic studies, all the negative values of ΔG° showed that all the adsorption processes of both adsorbents were spontaneous in nature.

Termiticidal Effects and Morpho-Histological Alterations in the Subterranean Termite (Odontotermes formosanus) Induced by Biosynthesized Zinc Oxide, Titanium Dioxide, and Chitosan Nanoparticles.

Recently, nanoparticles have been widely used in agricultural pest control as a secure substitute for pesticides. However, the effect of nanoparticles on controlling the subterranean termite Odontotermes formosanus (O. formosanus) has not been studied yet. Consequently, this study aimed to evaluate the effectiveness of some nanomaterials in controlling O. formosanus. The results showed that zinc oxide nanoparticles (ZnONPs), titanium dioxide nanoparticles (TiO2NPs), and chitosan nanoparticles (CsNPs) biosynthesized using the culture filtrate of Scedosporium apiospermum (S. apiospermum) had an effective role in controlling O. formosanus. Moreover, the mortality rate of O. formosanus after 48 h of treatment with ZnONPs, TiO2NPs, and CsNPs at a 1000 µg/mL concentration was 100%, 100%, and 97.67%, respectively. Furthermore, using ZnONPs, TiO2NPs, and CsNPs on O. formosanus resulted in morpho-histological variations in the normal structure, leading to its death. X-ray diffraction, UV-vis spectroscopy, Fourier transform infrared spectroscopy, scanning electron microscopy, dynamic light scattering, energy dispersive spectroscopy, and the Zeta potential were used to characterize the biosynthesis of ZnONPs, TiO2NPs, and CsNPs with strong activity against O. formosanus termites. Overall, the results of this investigation suggest that biosynthesized ZnONPs, TiO2NPs, and CsNPs have enormous potential for use as innovative, ecologically safe pesticides for O. formosanus control.

Assessing the climate adaptive potential of imported Chili in comparison with local cultivars through germination performance analysis.

BACKGROUND: The study offers insightful information about the adaptability of local and imported Chili cultivars. This experiment examines how three different chili cultivars Tanjung, Unpad, and Osaka perform in the germination and early growth phases while considering a wide range of environmental conditions. Research conducted in Jatinangor, Sumedang Regency, Indonesia, highlights the differences between cultivars and the varied possibilities for adaptability each variation possesses. RESULTS: Among them, Tanjung stands out as the most promising cultivar; its robust performance is demonstrated by its high germination index 91.7. Notable features of Osaka include the highest biomass output (1.429 g), the best water usage efficiency (WUE) at 0.015 g/liter, and the best distribution uniformity (91.2%) and application efficiency (73.6%) under different irrigation conditions. Tanjung's competitiveness is further evidenced by the fact that it trails Osaka closely on several metrics. Lower performance across criteria for Unpad suggests possible issues with flexibility. CONCLUSION: The value of this information becomes apparent when it comes to well-informed breeding programs and cultivation techniques, especially considering uncertain climate patterns and global climate change. This research contributes significantly to the body of knowledge, enabling well-informed choices for environmentally dynamic, sustainable chili farming.

Ulnar Bowing and Distal Radioulnar Joint Anatomy: A Three-Dimensional, In Situ Clinical Assessment.

Purpose: Distal radioulnar joint (DRUJ) injuries can be devastating and challenging to manage. The multiplanar curvature exhibited by the ulna impacts the morphology of the DRUJ, making it difficult to assess through two-dimensional radiographs alone. We used full-length, three-dimensional (3D) computed tomography angiography scans to assess the relationship between ulnar bowing, DRUJ ulnar variance (UV), and sigmoid notch angle. The goal of this study was to establish normal anatomic ranges for these landmarks to improve treatment for forearm traumas and DRUJ pathologies. Methods: Eighty-two intact upper extremity computed tomography angiography scans were examined and reconstructed into 3D models. We characterized ulnar bowing and DRUJ metrics using computer-aided design software. Measures of central tendency and Pearson correlation coefficients were calculated for comparative analysis. Results: The study yielded an average ulnar length of 272.3 mm. We identified the proximal ulnar bow at 36.7% of the bone's total length, possessing a depth of 10.3 mm, a proximal angle of 6.6°, and a distal angle of 3.9°. The distal ulnar bow appeared at 75.3% of the bone's length, characterized by a depth of 4.2 mm, a proximal angle of 2°, and a distal angle of 4.3°. In the coronal plane, the proximal angle of the proximal ulnar bow correlated positively with UV (r = 0.39, P < .001), whereas the distal angle of the distal ulnar bow correlated negatively (r = -0.48, P < .001). We also found significant correlations between the depths of both proximal and distal bows with UV (r = 0.38, P < .001; r = -0.34, P < .001, respectively). Moreover, UV within the DRUJ strongly correlated with the sigmoid notch angle (r = -0.77, P = .01). In contrast, the sagittal plane metrics did not show meaningful correlations with UV. Conclusion: Sagittal alignment and translation at the DRUJ articulation are directly related to ulna bowing at the distal ulna. A nuanced understanding of these 3D relationships can enhance preoperative planning when correcting ulnar-side pathology. Type of study/level of evidence: Therapeutic IV.

Biomembrane camouflaged nanoparticles: A paradigm shifts in targeted drug delivery system.

Targeted drug delivery has emerged as a pivotal approach within precision medicine, aiming to optimize therapeutic efficacy while minimizing systemic side effects. Advanced biomimetic membrane-coated formulations have garnered significant interest from researchers as a promising strategy for targeted drug delivery, site-specific accumulation and heightened therapeutic outcomes. Biomimetic nanotechnology is able to retain the biological properties of the parent cell thus are able to exhibit superior targeting compared to conventional formulations. In this review, we have described different types of cell membrane camouflaged NPs. Mechanism of isolation and coating of the membranes along with the applications of each type of membrane and their mechanism to reach the desired site. Furthermore, a fusion of different membranes in order to prepare hybrid membrane biomimetic NPs which could possess better efficacy is discussed in detail in the review. Later, applications of the hybrid membrane-cloaked NPs along with current development were discussed in detail along with the challenges associated with it. Although membrane-cloaked NPs are currently in the preliminary stage of development, there is a huge potential to explore this biodegradable and biocompatible delivery system.

Biomedical Applications of Green Synthesized Zinc Oxide and Magnesium-Doped Zinc Oxide Nanoparticles Using Aqueous Extract of Ziziphus Oxyphylla Leaves.

Zinc oxide (ZnO) and magnesium-doped zinc oxide (Mg-doped ZnO) nanoparticles (NPs) were synthesized using Ziziphus oxyphylla 's aqueous leaf extract as reducing agent. UV-Vis absorption peaks at 324 nm and 335 nm were indicative of ZnO and Mg-doped ZnO, respectively. FTIR absorption bands observed at 3238, 1043, 1400, 1401, 2186 and 2320 cm -1 suggested the presence of phenols, alcohols, saturated hydrocarbons, and possibly alkynes. X-ray diffraction (XRD), scanning electron microscopy (SEM) and energy dispersive X-ray (EDX) spectroscopy revealed pure, spherical and agglomerated NPs with average size of 35.9 nm (ZnO) and 56.8 nm (Mg-doped ZnO). Both NPs remained active against all bacterial strains with the highest inhibition zones observed against Proteus vulgaris (21.16±1.25 mm for ZnO and 24.1±0.76 mm for Mg-doped ZnO. EtBr fluorescence (cartwheel assay) indicated efflux pump blockage, suggesting its facilitation in the bacterial growth inhibition. Antioxidant potential, determined via DPPH radical scavenging assay, revealed stronger antioxidant potential for Mg-doped ZnO (IC [Formula: see text]/mL) than pure ZnO (IC [Formula: see text]/mL). Furthermore, both NPs showed antileishmanial activity against Leishmania tropica promastigotes (IC [Formula: see text]/mL for Mg-doped ZnO and 64.34±6.56 for ZnO), while neither NP exhibited significant hemolysis, indicating biocompatibility and further assessment for their drugability.

Effective Risk Assessment for Distal Radius Fractures: A Rigorous Multivariable Regression Analysis, Using a Novel 8-Item Modified Frailty Index.

Introduction Distal radius fractures (DRFs) are among the most common orthopaedic injuries. The prevalence of DRFs is increasing across all age groups but remains the second most common fracture in the elderly. The modified frailty index (MFI) often predicts morbidity and mortality in orthopaedic injuries. This study aims to determine the predictive value of MFI on complication rates following DRF and the patient length of stay and discharge outcomes. Methods We utilized our MFI to perform a retrospective analysis of the American College of Surgeons National Surgical Quality Improvement Program database. Results In a total of 22,313 patients, the average age was 46 ± 16. An increase in MFI led to an increase in the odds ratio of readmission and reoperation ( p < 0.001). MFI predicted complications, doubling the rate as the score increased from 1 to 2 ( p < 0.001). An MFI of 2 also led to a delayed hospital stay of 5 days ( p < 0.001), as well as an increase in the odds of patients not being sent home at discharge ( p < 0.001). Finally, life-threatening complications were also predicted with an increased MFI, the odds of a life-threatening complication increasing 488.20 times at an MFI of 3 ( p < 0.001). Discussion and Conclusion While surgical decision-making for frail patients with DRFs remains contentious, this novel 8-item MFI score was significantly associated with the probability of hospital readmission/reoperation, postoperative complications, and delayed hospital length of stay. Three new parameters were incorporated into our 8-item score compared with the conventional 5; hypoalbuminemia status (< 3.5 mg/dL), previous diagnosis of osteoporosis, and severe obesity (body mass index > 35) enhancing its sensitivity. Future studies are warranted for its prospective utility in ruling out postsurgical comorbidity.

QbD-Assisted Development and Optimization of Doxycycline Hyclate- and Hydroxyapatite-Loaded Nanoparticles for Periodontal Delivery.

The current research aims to develop a carrier system for the delivery of a matrix metalloproteinase (MMP) inhibitor along with a bioceramic agent to the periodontal pocket. It is proposed that the present system, if given along with a systemic antibiotic, would be a fruitful approach for periodontitis amelioration. To fulfill the aforementioned objective, a doxycycline hyclate- and hydroxyapatite-adsorbed composite was prepared by a physical adsorption method and successfully loaded inside sodium alginate-chitosan nanoparticles and optimized based on particle size and drug content. Optimized formulation was then subjected to different evaluation parameters like encapsulation efficiency, hydroxyapatite content, ζ potential, surface morphology, in vitro drug release, cell line studies, and stability studies. For the optimized formulation, particle size, polydispersity index (PDI), entrapment efficiency, ζ potential, and drug content were found to be 336.50 nm, 0.23, 41.77%, -13.85 mV, and 14.00%, respectively. The surface morphology of the placebo and adsorbed composite-loaded nanoparticles as observed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) revealed the spherical shape and rough surface of the particles. In gingival crevicular fluid (GCF) 7.6, a sustained drug release profile was obtained up to 36 h. In vitro % viability studies performed on murine fibroblast cells (NIH3T3) and human periodontal ligament (hPDL) cell lines confirmed the proliferative nature of the formulation. Also, when subjected to stability studies for 4 weeks, particle size, PDI, and drug content did not vary considerably, thereby ensuring the stable nature of nanoparticles. Henceforth, sodium alginate-chitosan nanoparticles appeared to be a good carrier system for doxycycline hyclate and hydroxyapatite for periodontal therapy. If given along with a system antibiotic, the system will serve as a fruitful tool for infection-mediated periodontal regeneration and healing.

The Impact of Military Tobacco Control Policy: A Systematic Review.

INTRODUCTION: Tobacco use is synonymous with the military. Despite that military personnel are trained to follow commands, opportunities exist to implement various tobacco control strategies. We conducted a systematic review to evaluate the impact of tobacco control policy employed in military settings. MATERIALS AND METHODS: We searched for published English articles in Medline, Web of Science, Scopus, and Google Scholar databases using relevant subject headings without year restriction. We included randomized controlled trials, nonrandomized controlled trials, case-control, cohort, controlled before and after, and uncontrolled before and after studies evaluating the impact of tobacco control policy in the military population. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, three independent reviewers independently screened initially identified articles, reviewed the full text, and extracted the data and any disagreements resolved by consensus after data recheck. Five reviewers used a validated tool to assess the quality of the included studies. The primary outcome was the reduction of any tobacco or nicotine-contained products (TNCPs) use among the troops. The impacts of the tobacco control policy were synthesized and analyzed qualitatively. This study is registered with the International Prospective Register of Systematic Review (CRD42022314117). RESULTS: Fourteen studies were included in the analysis from 5372 studies screened. Most of the studies were from the USA, and fractions were from Thailand, France, and Taiwan. These studies were methodologically heterogeneous. Most studies employed a total ban policy on TNCP use during basic military training or operational deployment as the primary strategy. Other methods utilized were the brief tobacco intervention, targeted treatment, support, and counseling provided through telephone or mailing systems, the adjunctive behavioral intervention, providing free nicotine gum, the "Pharsai clinic", active and regular smoking restriction, and interventions aimed at intrapersonal, interpersonal, and organizational levels. There is a moderate quality of evidence that the tobacco control policies effectively reduced the prevalence of TNCP use, increased the cessation rate, reduced the intake, and lowered the dependency. The adjunctive interventions provided after the total ban on TNCP use may increase its effectiveness. However, findings from this review need to be carefully considered as the definition of TNCP use status was not universal between studies and lacked a biochemical validation procedure. CONCLUSIONS: There is reasonable evidence to support that the tobacco control policy employed in the military population has multiple positive impacts in reducing the prevalence of TNCP use, increasing the cessation rates, reducing the intake, and lowering dependency. Other evidence-based strategies need to be fully utilized to materialize the tobacco endgame.

Opening Wedge Osteotomy for the Treatment of Pediatric Radial Neck Malunion and Anterior Radiocapitellar Dislocation: A Case Report.

Radial neck fractures are common injuries of the elbow in the pediatric patient. Surgical intervention is recommended for significant angulation and displacement or mechanical blocks to motion. Radial neck malunion is a rare complication and may result in altered joint mechanics and, if severe, joint incongruency. Dislocation of the radial head has yet to be reported in this population after radial neck malunion. Treatment for radial neck malunions with dislocation varies and can include radial head excision or radial neck osteotomy. Outcomes after radial neck osteotomy is limited to case reports and small cases series. We present a case report of pediatric patient with radial neck malunion and anterior radiocapitellar dislocation treated with joint realignment via opening wedge osteotomy. To our knowledge, this is the first report of a pediatric case with radial head dislocation secondary to neck malunion and the first described report using this technique.

Utilization of Quince (Cydonia oblonga) Peel and Exploration of Its Metabolite Profiling and Cardioprotective Potential Against Doxorubicin-Induced Cardiotoxicity in Wistar Rats.

Quince (Cydonia oblonga Mill.) is a pomaceous fruit that is typically processed into jams, jellies, and marmalade. The byproduct, i.e., the quince peel emanated from the processing industry, can be upcycled, ensuring zero waste policy and resulting in a sustainable food system. In our study, the quince peel was explored for in vitro phytochemical analysis and in vivo cardioprotective potential. Two diverse extractions (ultrasonication and reflux) and four different solvents (aqueous, ethanolic, hydroethanolic, and methanolic) were used for the extraction of quince peel and assessed for the phytochemical and antioxidant study. Among all the evaluated extracts, hydroethanolic quince extract extracted through the reflux extraction method showed the maximum phenolic (27.23 ± 0.85 mg GAE/g DW) and flavonoid (16.5 ± 1.02 mg RE/g DW) content. The maximum antioxidant potential (DPPH) with an IC50 value of 204.8 ± 2.24 µg/mL was noted for the hydroethanolic extract. This best active extract was then subjected to HPTLC, UPLC-MS, mineral, and FTIR analysis to study the metabolic profiling and inorganic composition and to confirm the presence of bioactives. Additionally, the in vivo study was done in rats using doxorubicin (DOX)-induced cardiotoxicity. The rats were given extracts orally at 160 and 320 mg/kg bw for 30 days. ECG analysis was done at the termination of the experiment. Besides this, the lipid profile, blood serum parameters (CK-MB, LDH, AST), and tissue parameters (MDA, SOD, GSH, CAT) were analyzed. The DOX-treated group unveiled a substantial variance (p < 0.001) in all the parameters in contrast to the normal control group and extract control groups. However, the pretreated groups substantially alleviated the DOX-induced changes in all the parameters. Additionally, recuperation in histopathological alterations of the cardiac tissue in contrast to the DOX-induced toxicity was also seen in the pretreated groups. Thus, it could be said that the cardioprotective activity of the quince peel extract attributed to the presence of phytoconstituents counteracted the DOX-induced cardiotoxicity and assisted in the restoration of the cardiac injury in rats.

Inpatient or outpatient total elbow arthroplasty: a comparison of patient populations and 30-day surgical outcomes from the American College of Surgeons National Surgical Quality Improvement Program.

BACKGROUND: Total elbow arthroplasty (TEA) is uncommon, but growing in incidence. Traditionally an inpatient operation, a growing number are performed outpatient, consistent with general trends in orthopedic surgery. The aim of this study was to compare TEA outcomes between inpatient and outpatient surgical settings. Secondarily, we sought to identify patient characteristics that predict the operative setting. METHODS: Patient data were collected from the American College of Surgeons National Quality Improvement Program. Preoperative variables, including patient demographics and comorbidities, were recorded, and baseline differences were assessed via multivariate regression to predict operative setting. Multivariate regression was also used to compare postoperative complications within 30 days. RESULTS: A total of 468 patients, 303 inpatient and 165 outpatient procedures, were identified for inclusion. Hypoalbuminemia (odds ratio [OR], 2.5; P=0.029), history of chronic obstructive pulmonary disorder or pneumonia (OR, 2.4; P=0.029), and diabetes mellitus (OR, 2.5; P=0.001) were significantly associated with inpatient TEA, as were greater odds of any complication (OR, 4.1; P<0.001) or adverse discharge (OR, 4.5; P<0.001) and decreased odds of reoperation (OR, 0.4; P=0.037). CONCLUSIONS: Patients undergoing inpatient TEA are generally more comorbid, and inpatient surgery is associated with greater odds of complications and adverse discharge. However, we found higher rates of reoperation in outpatient TEA. Our findings suggest outpatient TEA is safe, although patients with a higher comorbidity burden may require inpatient surgery. Level of evidence: III.

Development of Bedaquiline-Loaded SNEDDS Using Quality by Design (QbD) Approach to Improve Biopharmaceutical Attributes for the Management of Multidrug-Resistant Tuberculosis (MDR-TB).

Background: The ever-growing emergence of antibiotic resistance associated with tuberculosis (TB) has become a global challenge. In 2012, the USFDA gave expedited approval to bedaquiline (BDQ) as a new treatment for drug-resistant TB in adults when no other viable options are available. BDQ is a diarylquinoline derivative and exhibits targeted action on mycobacterium tuberculosis, but due to poor solubility, the desired therapeutic action is not achieved. Objective: To develop a QbD-based self-nanoemulsifying drug delivery system of bedaquiline using various oils, surfactants, and co-surfactants. Methods: The quality target product profile (QTPP) and critical quality attributes (CQAs) were identified with a patient-centric approach, which facilitated the selection of critical material attributes (CMAs) during pre-formulation studies and initial risk assessment. Caprylic acid as a lipid, propylene glycol as a surfactant, and Transcutol-P as a co-surfactant were selected as CMAs for the formulation of bedaquiline fumarate SNEDDS. Pseudo-ternary phase diagrams were constructed to determine the optimal ratio of oil and Smix. To optimize the formulation, a Box-Benkhen design (BBD) was used. The optimized formulation (BDQ-F-SNEDSS) was further evaluated for parameters such as droplet size, polydispersity index (PDI), percentage transmittance, dilution studies, stability studies, and cell toxicity through the A549 cell. Results: Optimized BDQ-F-SNEDDS showed well-formed droplets of 98.88 ± 2.1 nm with a zeta potential of 21.16 mV. In vitro studies showed enhanced drug release with a high degree of stability at 25 ± 2 °C, 60 ± 5% and 40 ± 2 °C, 75 ± 5%. Furthermore, BDQ-F-SNEDDS showed promising cell viability in A549 cells, indicating BDQ-F-SNEDDS as a safer formulation for oral delivery. Conclusion: Finally, it was concluded that the utilization of a QbD approach in the development of BDQ-F-loaded SNEDDS offers a promising strategy to improve the biopharmaceutical properties of the drug, resulting in potential cost and time savings.

It Is All about Probiotics to Control Cervical Cancer.

Cervical cancer (CC) is the fourth most common malignancy in female patients. "Human papillomavirus" (HPV) contamination is a leading cause of all forms of cervical cancer, accounting for an expected 570,000 reported incidents in 2018. Two HPV strains (16 and 18) are responsible for 70% of CC and pre-cancerous cervical abnormalities. CC is one of the foremost reasons for the malignancy death rate in India among women ranging from 30 to 69 years of age in India, responsible for 17% of all cancer deaths. Currently approved cervical cancer treatments are associated with adverse reactions that might harm the lives of women affected by this disease. Consequently, probiotics can play a vital role in the treatment of CC. It is reflected from various studies regarding the role of probiotics in the diagnosis, prevention or treatment of cancer. In this review article, we have discussed the rationale of probiotics for treatment of CC, the role of probiotics as effective adjuvants in anti-cancer therapy and the combined effect of the anti-cancer drug along with probiotics to minimize the side effects due to chemotherapy.

Skin cancer: understanding the journey of transformation from conventional to advanced treatment approaches.

Skin cancer is a global threat to the healthcare system and is estimated to incline tremendously in the next 20 years, if not diagnosed at an early stage. Even though it is curable at an early stage, novel drug identification, clinical success, and drug resistance is another major challenge. To bridge the gap and bring effective treatment, it is important to understand the etiology of skin carcinoma, the mechanism of cell proliferation, factors affecting cell growth, and the mechanism of drug resistance. The current article focusses on understanding the structural diversity of skin cancers, treatments available till date including phytocompounds, chemotherapy, radiotherapy, photothermal therapy, surgery, combination therapy, molecular targets associated with cancer growth and metastasis, and special emphasis on nanotechnology-based approaches for downregulating the deleterious disease. A detailed analysis with respect to types of nanoparticles and their scope in overcoming multidrug resistance as well as associated clinical trials has been discussed.

Advanced targeted drug delivery by bioengineered white blood cell-membrane camouflaged nanoparticulate delivery nanostructures.

Targeted drug delivery has emerged as a pivotal approach within precision medicine, aiming to optimize therapeutic efficacy while minimizing systemic side effects. Leukocyte membrane coated nanoparticles (NPs) have attracted a lot of interest as an effective approach for delivering targeted drugs, capitalizing on the natural attributes of leukocytes to achieve site-specific accumulation, and heightened therapeutic outcomes. An overview of the present state of the targeted medication delivery research is given in this review. Notably, Leukocyte membrane-coated NPs offer inherent advantages such as immune evasion, extended circulation half-life, and precise homing to inflamed or diseased tissues through specific interactions with adhesion molecules. leukocyte membrane-coated NPs hold significant promise in advancing targeted drug delivery for precision medicine. As research progresses, they are anticipated to contribute to improved therapeutic outcomes, enabling personalized and effective treatments for a wide range of diseases and conditions. The review covers the method of preparation, characterization, and biological applications of leucocytic membrane coated NPs. Further, patents related factors, gap of translation from laboratory to clinic, and future prospective were discussed in detail. Overall, the review covers extensive literature to establish leucocytic membrane NPs for targeted drug delivery.