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Background: Wounds remain the most important cause of postoperative mortality and morbidity and generate considerable additional social and healthcare costs. Most wounds are caused by various coliforms, Enterococcus fecalis, Proteus sp., and multidrug resistant Staphylococcus aureus. Wound is one of the leading cause of infections in the under developed and developing countries than developed nations. Methods: A total of 43 samples associated with bacteremia and wound infection were collected. Biochemical characterization and culture characteristics of the drug resistant isolates were studied using MacConkey agar, blood agar and mannitol-salt agar. Antibiotic susceptibility analysis of the isolated strains was performed by disc diffusion method using various antibiotics. Prevalence of dug resistance among bacteria isolated from the wound was studied. The ability of Beta lactamase antibiotic producing bacterial strains were analyzed. Results: A total of 168 bacterial strains were isolated showed high resistant towards ampicillin (89%), ciprofloxacin (90.8), cefepine (90.5), piperacillin (91.8), oxacillin (92.5), and imipenem (96.5). The isolated bacterial strains showed monobacterial as well as polybacterial growth on the surface of the wound. The isolated bacterial strains revealed 89% sensitivity against norfloxacin and 94.9 sensitivity against vancomycin. About 26% of bacterial strains degraded quinolones, whereas only 14% clinical isolates showed their ability to degrade aminoglycosides. A total of 27% bacteria degraded tetracycline and 51% of isolates degraded carbapenems compounds. Interestingly, E. faecalis was resistant against antibiotics such as, Oxacillin, Nalidic acid, Ofloxacin, Erythromycin, Norfloxacin, Ciprofloxacin, Ampicillin, Tetracycline, Cefepine, Amikacin, Cefurooxime, Vancomycin, Piperacillin, Imipenem and Gentamycin. Moreover, Proteus species was resistant against certain numbers of antibiotics namely, Ampicillin, Piperacillin, Oxacillin, Nalidic acid, Tetracycline, Erythromycin, Cefurooxime, Nitrofurantoin, Vancomycin and Imipenem. Conclusions: The isolated bacterial strains were resistant against various drugs including vancomycin. Staphylococci, and E. faecalisis strains showed resistance against various classes of antibiotics.

Background: The current health concern to the entire world is the chronic respiratory disease caused by coronavirus 2 (COVID-19). A specific treatment or proper therapy is still lacking, and the investigations from across the world for proper drug/vaccine development towards disease control are in progress. The Coronavirus replication takes place by the conversion of the polypeptide into functional protein and this occurs due to the key enzyme Main protease (Mpro). Therefore, identification of natural and effective Mpro inhibitors could be a safe and promising approach for COVID-19 control. Methods: The present in silico study evaluates the effect of bioactive compounds found in Eucalyptus and Corymbia species essential oil on Mpro by docking. Molecular docking of the major seven compounds of essential oil (citronellol, alpha-terpineol, eucalyptol, d-limonene, 3-carene, o-cymene, and alpha-pinene) with Mpro was studied by AutoDock 4.2, and the properties were analysed by PreADMET and Biovia Discovery Studio visualizer. Results: The calculated parameters such as binding energy, hydrophobic interactions, and hydrogen bond interactions of 6LU7 (Mpro) with Eucalyptus and Corymbia volatile secondary metabolites represented its scope as an effective therapy option against covid-19. Among the docked compounds, eucalyptol shows the least binding energy without toxicity. Conclusions: The outcome of this study reported that the essential oil of Eucalyptus and Corymbia species, mainly eucalyptol can be utilized as a potential inhibitor against COVID-19 and also it can be used in its treatment. Hence, further analysis was required to explore its potential application in medicine.

The dysfunction of left atrial appendage (LAA) is prone to form thrombus when atrial fibrillation (AF) sustained more than 48 h. Traditional 2D-TEE (transesophageal echocardiography) can not accurate evaluate the function of LAA. The purpose of this study is to analyze the relationship of LAA function parameters and thrombus formation in patients with non-valvular atrial fibrillation (NVAF) by real-time three-dimensional transesophageal echocardiography (RT-3D-TEE). High risk patients can be identified according to the characteristics of ultrasonic index in patients with left atrial appendage thrombosis, which has important clinical value and significance in the risk assessment, guiding treatment and judging prognosis. We examined the relationship between the echocardiographic parameters of LAA function and the incidence of thrombus in 102 NVAF patients. They underwent RT-3D-TEE and left atrial appendage thrombus (LAAT)/severe spontaneous echocardiographic contrast (SSEC) was found in 67 patients (thrombus group) but absent in the remaining 35 patients (non-thrombus group). After measured by QLAB software, the LAA functional parameters were significantly associated with LAAT/SEC formation. Univariate analysis indicated that AF time, LAD, LVEF, LAA-OAmax, LAAVmax, LAAVI and LAAEF demonstrated a positive association (P

Garlic (Allium sativum L.), is a predominant spice, which is used as an herbal medicine and flavoring agent, since ancient times. It has a rich source of various secondary metabolites such as flavonoids, terpenoids and alkaloids, which have various pharmacological properties. Garlic is used in the treatment of various ailments such as cancer, diabetes and cardiovascular diseases. The present study aims to explore the plausible mechanisms of the selected phytocompounds as potential inhibitors against the known drug targets of non-small-cell lung cancer (NSCLC). The phytocompounds of garlic were identified by gas chromatography-mass spectrometry (GC–MS) technique. Subsequently, the identified phytocompounds were subjected to molecular docking to predict the binding with the drug targets, epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) and group IIa secretory phospholipase A2 (sPLA2-IIA). Molecular dynamics is used to predict the stability of the identified phytocompounds against NSCLC drug targets by refining the intermolecular interactions formed between them. Among the 12 phytocompounds of garlic, three compounds[1,4-dimethyl-7-(1-methylethyl)-2-azulenyl]phenylmethanone, 2,4-bis(1-phenylethyl)-phenol and 4,5–2 h-oxazole-5-one,4-[3,5-di-t-butyl-4-methoxyphenyl] methylene-2-phenyl were identified as potential inhibitors, which might be suitable for targeting the different clinical forms of EGFR and dual inhibition of the studied drug targets to combat NSCLC. The result of this study suggest that these identified phytocompounds from garlic would serve as promising leads for the development of lead molecules to design new multi-targeting drugs to address the different clinical forms of NSCLC.

This context was investigated to assess the in vitro antioxidant, anti-diabetic, anti-obesity, and angiotensin-converting enzyme (ACE) inhibition traits of Punica granatum fruits peel extract. Initially, among various extracts tested, aqueous and ethanolic peel extracts depicted the presence of diverse phytoconstituents. In vitro antioxidative properties of peel extracts were determined using standard methodologies. Results showed that aqueous and ethanolic extracts had IC50 values of 471.7 and 509.16 μg/mL, respectively in terms of 1,1,diphenyl 2,2,picrylhydrazyl scavenging. Likewise, IC50 values of aqueous and ethanol extract were obtained as 488.76 and 478.47 μg/mL towards the degradation of hydrogen peroxide. The ethanolic extract exhibited the highest inhibition of α-glucosidase by showing activity of 53.34 ± 2.0 to 15.18 ± 1.4 U/L in a dose dependent manner (100–1000 µg/mL). Ethanolic extract was reported as the most active inhibitor of lipase with an IC50 value of 603.50 µg/mL. Ethanolic extract showed increased inhibition of ACE in a concentration dependent manner (100–1000 µg/mL) with IC50 value of 519.45 µg/mL. Fourier transform-infrared spectrum revealed the availability of various functional groups in the ethanolic extract of peel. Gas chromatography-mass spectrometry chromatogram of peel extract illustrated 23 diversified chemical constituents including 1,2,3,4-butanetetrol, Dimethyl sulfone, 9-octadecenamide, and Pentadecanoic acid as predominant compounds. In summary, P. granatum fruits peel extract revealed promising antioxidant, anti-diabetic, anti-obesity, and anti-hypertensive properties.

The present study aimed to analyze the nephroprotective property of violacein obtained from the bacterium, Chromobacterium violaceum. The nephrotoxicity in the animal model was induced by gentamicin, potassium dichromate, mercuric chloride, and cadmium chloride-induced nephrotoxicity in the Wistar rats was analyzed by measuring the serum creatinine, uric acid, and urea level. The present investigation revealed the nephroprotective property on convoluted proximal tubule (S1 and S2 segments) and the straight proximal tubule (S3 segment). Also, violacein significantly improved the renal function by the renal protective property on S2 segment of proximal tubule from the nephrotoxicity stimulated by mercuric chloride, potassium dichromate, cadmium chloride and gentamicin in animal models. Animal model studies revealed that violacein at 20 and 40 mg/kg p.o improved the renal function and significantly reduced the increased amount of uric acid, creatinine, and blood urea compared to the control.

Helicanthes elasticus (Desv.) Danser is a common type of mistletoes of Indian origin. In Indian traditional and folklore medicines the plant is claimed to possess a range of medicinal values such as immunomodulator, anti-diabetic and anti-microbial properties. However, there is no experimental proof for its therapeutic claim. The aqueous and alcoholic extracts of H. elastica were evaluated for its immuno-modulatory effect on antibody formation against sheep red blood cells and on cell mediated immunity of immunological paw edema model. Ethanolic and aqueous extracts have shown dose dependent elevation in the antibody titer value in comparison to control group at 14th and 21st day of sensitization (**p

Cocos nucifera L is well-known for its edible and medicinal uses; multiple products from the different parts of the plant are being used by various communities in India. A less explored product is the coconut haustorium, the solid endosperm portion, which is highly nutritious. The present study first time evaluated the antioxidant, anti-inflammatory and cytoprotective properties of methanolic extract of Coconut haustorium (CHE). The cytoprotective effect of CHE was evaluated in hydrogen peroxide/malondialdehyde-induced toxicity IEC-6 (normal intestinal cell). Initially the biologically safe concentration of CHE and IC50 value of hydrogen peroxide and malondialdehyde was estimated by MTT assay. Treatment with H2O2 and MDA led to glutathione depletion and reduction in the catalase and glutathione reductase activity; which resulted in the increased oxidative stress and thereby cell death. Pretreatment with the different concentrations (10, 20 and 40 µg/mL) of CHE offered significant and dose-dependent protection against the toxicity induced by hydrogen peroxide and malondialdehyde. It is observed that the CHE pretreatment restored the antioxidant enzyme activities and GSH levels back to normal; the improvement in antioxidant status may be through the upregulation of Nrf2/HO1 pathway as observed in CHE pretreated cells. The anti-inflammatory potential was evaluated in the lipopolysaccharide (LPS-1 µg/mL) induced model in macrophages (Raw 264.7 cells). CHE pretreatment reduced the LPS- induced release of cytokines such as IL-1β, IL-6, and tumor necrosis factor-alpha (TNF-α). The results indicated the antioxidant, anti-inflammatory and cytoprotective effect of less explored haustorium from Coconut.

In this study, 104 bacteria were isolated from the gut of Penaeus indicus. The morphologically different bacterial isolates were screened for probiotic properties. The strain D5 showed potent activity against various bacteria. The isolated strain Bacillus subtilis showed 17 mm zone of inhibition against Bacillus sp., 19 mm against Pseudomonas sp., 22 mm against Vibrio sp., and 22 mm against Micrococcus sp. The bacterial growth and bacterocin production in relation with incubation time was evaluated. Bacteriocin production was found to be high at the stationary phase and reduced considerably after fifth day. Bacterial growth and bacterocin production was maximum at pH 7.0 and optimum between pH 6.0 and 8.0. Incubation temperature is one of the important factors which significantly influences on the growth and production of bacteriocin. Bacterial growth and bacterocin production (17 ± 2 mm) were maximum at 30 °C. Glucose stimulated growth and bacterocin production (21 ± 3 mm). Among the supplemented nitrogen sources, glycine positively influenced on growth and metabolite production. In this study, bacteriocin supplemented diet enhanced the growth than control shrimp Bacteriocin was administered at various doses ranged between 10 and 50 mg/100 gm level. Shrimp length was 3.3 ± 0.13 cm and shrimp weight was 9.7 ± 0.12 g in 100 mg. The present finding revealed enhanced growth at high bacteriocin concentration. At 2 × 102 CFU/100 g probiotics in feed, the juvenile shrimp attained 16.8 ± 0.11 g after 40 days. The weight gain was 16.8 ± 0.11 CFU/100 g at 10 × 102 CFU/100 g probiotic concentration. Keywords: Shrimp gut, Bacillus subtilis, Probiotics, Penaeus indicus, Feed conversion ratio

Fenvalerate is widely used insecticide that severely causes toxicological effects in various aquatic organisms especially in fish. Physiochemical factors of water influenced fenvalerate toxicity. This study investigated physiochemical content of water, the effects of fenvalerate on mortality, changes in protein profile in the gut of Zebra fish and digestive enzymatic changes after 28 days of exposure. Zebra fish was exposed to ranges of fenvalerate and LC50 value was determined. Alkaline pH of the water and high temperature critically influenced mortality. The sub lethal concentration of fenvalerate decreased total protein content in various organs and induced elevated level of free aminoacids. Fenvalerate affected major digestive enzymes activity in the gut of Zebra fish. Protease and amylase assay revealed 39 ± 2.4% protease activity loss and 24.5 ± 5.5% amylase activity loss due to fenvalerate toxicity. Fenvalerate induced disintegration of enzymes from the gut at sub lethal concentration. Fenvalerate reduce the enzyme activity of proteases and amylases significantly. The present finding suggests that accumulation of fenvalerate critically alter not only the biochemical changes in the intestine, but also the specificity of protease and amylase towards various substrates. Keywords: Freshwater, Danio rerio, Fenvalerate, Sub lethal, Mortality, Protease, Amylase

The main objective of the present study is to determine lead toxicity on various sizes of zebra fish in soft and hard water. Lead toxicity analysis was carried out in the laboratory trials for four days at various concentrations for the determination of LC50 value. Zebra fish was grouped into various sizes (G1-G4) and treated with lead for 96 h. Lead induced toxicity and induced various behavioural changes in Zebra fish. In the case of G1 (1.5 ± 0.2 cm length) fish the LC50 values ranged from 27.2 ± 1.8 mg/L to 9.7 ± 1.3 mg/L. In G2 (2.0 ± 0.2 cm length) fish, the LC50 value was 37.01 ± 2.3 mg/L and it reduced as 32.03 ± 3.4 mg/L after 48 h. In G3 group (2.5 ± 0.2 cm length fish), LC50 value was 38.78 ± 2.4 mg/L after 24 h treatment and this value decreased as 33.18 ± 1.1 mg/L after 48 h. After 72 h, LC50 value was 27.2 ± 2.1 mg/L and this value decreased considerably after 96 h (18.3 ± 2.1 mg/L) in G4 (3.0 ± 0.2 cm length) fish. Further, G4 fish was treated with lead in hard water and LC50 value was analyzed. LC50 value was observed as 28.62 ± 2.7 mg/L in hard water and the same fish group (G4) showed 18.3 ± 2.1 mg/L after 96 h. Toxicity analysis revealed that lead is less toxic in hard water than in soft water. Keywords: Lead, Toxicity, Water hardness, Zebra fish

In this study, phyto-constituents, anti-bacterial and anticancer activity of Azadirachta indica A. Juss and Melia azedarach Linn was analyzed. High Performance Liquid Chromatography (HPLC) and Thin Layer Chromatography (TLC) fingerprint profile of methanol extract of A. indica and M. azedarach was carried out. The present findings showed the presence of phytochemicals such as, steroids, alkaloids, phenols, flavonoids, saponins, tannins, anthraquinone and aminoacids in A. indica and M. azedarach extracts. HPLC profiling of methanolic extract of A. indica and M. azaderach revealed eleven and ten fractions of compounds were visualized in the form of peak. In TLC methanolic extract of A. indica was separated by eight distinct phenolic and three steroidal bands and M. azaderach showed sixteen distinct phenolic and three different steroidal bands. In antibacterial activity, Among the various extracts 50 µg/ml methanolic extracts of A. indica showed high activity against K. pneumoniae (14 mm) and M. azedarach showed high activity against S. aureus (15 mm). The results suggest that the crude methanolic extracts of A. indica and M. azedarach possess significant phytochemical properties compared to other extracts and hence the phytochemicals of M. azedarach and A. indica can be exploited for plant based anticancer and antimicrobial agents in the near future. Keywords: Medicinal plants, Azadirachta indica, Melia azedarach, Phytochemicals, Anticancer

Background: Environmental exposure to toxicants poses high risk to develop reproductive and developmental chronic toxicity in man. Toluene is one of the commonest industrial agents whose exposure is attributed with potential to induce reproductive and developmental toxicity. Since they contaminate the immediate environment of air and water to which humans are exposed, its containment is of great public health importance. Conventional treatment modalities fail owing to the difficulty to detect these highly volatile agents in environment and human body. The peril of such hazardous exposures is evident only when irreversible structural and functional damages have incurred. In such instances, prevention gains an upper hand when compared to therapeutic interventions. Several natural compounds derived from medicinal herbs possess potential to curb toxicities induced by such xenobiotic agents. Among them Boerhavia diffusa Linn. is a widely distributed and common herb attributed with antitoxic potential and capability for antioxidant defence. A study was performed on the prophylactic efficacy of aqueous extract of B. diffusa in curbing toluene induced developmental toxicity in Drosophila melanogaster. Methods: The study consisted of a preliminary phytochemical screening and HPTLC profiling of B. diffusa aqueous extract (BDAE). LC50 of toluene was assessed and a sublethal dose of 200 ppm was fixed for the study. Four doses of BDAE; 25, 50, 100 and 200 mg/ml designated as Low dose, medium dose 1, medium dose 2 and high dose was used for the study. The parameters used for the study included the determination of larval period, pupal period, percentage of egg hatching, morphometric analysis of egg, larvae, pupae and adults, fertility, fecundity, lifespan and levels of antioxidant enzymes such as catalase, glutathione-S-transferase and superoxide dismutase. Results: The phytochemical and HPTLC characters were as per the pharmacopoeial standards. LC50 of toluene was found to be 430 ppm in this study. BDAE at medium dose 2 and high dose significantly prevented the deterioration of reproductive and developmental toxicity parameters of larval period, pupal period, percentage of egg hatching, morphometric characters of larva, pupa and adult, fertility, fecundity and lifespan in drosophila. Also the drug significantly elevated the levels of antioxidant enzymes. Conclusion: Toluene exposure during lifetime is inevitable. B. diffusa, equipped with its rich active ingredients prevented toluene induced developmental and reproductive toxicity in Drosophila. This medicinal herb provides a ray of hope in preventing environmental toxin induced reproductive and developmental toxicity. Keywords: Developmental toxicity, Reproductive toxicity, Toluene, Boerhavia diffusa, Antioxidant

This study aimed to inspect the hierarchically structured spherical-like hematite (α-Fe2O3) nanoparticles synthesize by simple, low temperature solution combustion process. The uniformly distributed α-Fe2O3/carbon nanocomposite (α-Fe2O3/C nanocomposite) was prepared by incorporating carbon nanoplates into sphere-like α-Fe2O3 nanoparticles. The synthesized nanomaterials were characterized using various techniques such as XRD, FESEM, and EDS. The cytotoxicity of the material was evaluated by MTT assay and nuclear imaging based on the cell morphological changes on both human lung cancerous cell line A549 and chang liver as non cancerous cell line. The results demonstrated that the pure and composite material exhibited above 70% viability on non-cancerous cell line and around 60% inhibition on A549 lung cancer cell line indicates the α-Fe2O3/C nanocomposite is biocompatible and can be used for biological applications and anticancer therapy. Cell death induced by α-Fe2O3, carbon nanoplates and α-Fe2O3/C nanocomposites was further evidenced with DAPI. Keywords: Biocompatibility, Carbon nanoplates, Cytotoxicity, α-Fe2O3, α-Fe2O3/C nanocomposites

Extensive application of pesticide in agricultural field affects the enzymatic activity of non-target animals, including fishes. In this study, the impact of sublethal concentration of fenvalerate on marker enzymes of freshwater Zebra fish was evaluated. Pesticide-induced stress can specifically affect non target fishes, through elevated level of reactive oxygen species which is responsible for biochemical, cell metabolism and physiological activities. The oxidative stress mediated by fenvalerate at sub lethal concentrations after 28 days of exposure of Zebra fish. Following 28 days of exposure of pesticide, catalase, superoxide dismutase, aspartate amino transferases, alanine amino transferase, alkaline phosphatase and acid phosphatase were assessed. Results revealed reduction of superoxide dismutase activity after 28 days of exposure in sub lethal concentration of fenvalerate in liver and gills. In liver, catalase activity was found to be less in fenvalerate exposed fish than control fish. In liver, increase of 75.75% aspartate amino transferase and 38% increase in alanine amino transferase in gills. SGPT activity was relatively higher than SGOT suggests more contribution of phyruvalate than oxaloacetate formation. Fenvalerate induced changes in acid phosphatase and alkaline phosphatase activity in the liver and gills of Zebra fish after four weeks of exposure. Fenvalerate induced expression of various stress proteins in gill, liver, followed by muscle. Some proteins lost its intensity due to fenvalerate toxicity. Result revealed that enzyme assays and SDS-PAGE analysis for protein subunits determination is relevant tool to monitor stress in freshwater ecosystem. The findings suggest that in monitoring fenvalerate toxicity programme, enzyme activities can be potent diagnostic tool for fenvalerate induced toxicity. Keywords: Pyrethroid, Fenvalerate, Fish, Toxicity, Metabolic enzymes, Stress

Background: Inflammation and pain triggers several pathological illnesses. Synthetic drugs used for the controlling of inflammatory conditions convey significant toxic effects. Global scientific community continually attempt to improve effective, economic and harmless naturally derived remedies against inflammation and pain. The present study aimed to quantify the phytochemical constituents of the freshly cultivated Spirulina and targeted to examining the anti-inflammatory and analgesic activity of Spirulina extract (SE) derived from Arthrospira platensis. Methods: The anti-inflammatory effect of SE was evaluated in animal models including carrageenan-induced rat hind paw oedema, and cotton pellet-induced granuloma formation. Analgesic effects of SE were evaluated by acetic acid induced writhing response and hot plate test. Results: Phytochemical quantification guided to identify seven carbohydrates, thirteen amino acids, eleven fatty acids and polyphenolic compounds respectively. The results indicated that SE significantly attenuated carrageenan-induced hind paw oedema, and cotton pellet-induced granuloma. Preliminary molecular mechanistic studies established that SE decreased the productions of TNF-α, IL-1β, IL-6, PGE2 and NO, and suppressed the activities of COX-2 and iNOS. Conclusion: These results provide a strong scientific foundation for the anti-inflammatory and analgesic activities of SE against different studies in animal models. Keywords: Arthrospira platensis, Spirulina extract, Phytochemicals, Anti-inflammatory, Analgesic, Oedema

Present state-of-the-art focusing on the formulates multifunctional hollow mesoporous silica nanoparticles (HMSNs) represent a reservoir for encapsulating warhead of active entail Nimbin (NB) into the hollow core and the surface modified by PEI-PLA by electrostatic interaction. The fabricated hollow mesoporous silica (HMSN) nano drug framework is amended with polyethyleneimine (PEI)-poly lactic acid (PLA) with carboxylic group terminus used to tag liver tumour-targeting agent galactosamine (GAL). Thus, with surface modified HMSNs capable of internalization into cancer cells, the ability of NB to discharge into cancerous cells influenced by environmental pH value. The emerging active ingredient firmly suppresses the expression of the P13/Akt pathway to induce apoptosis by creating DNA fragmentation, caspase activation and reactive oxygen species (ROS). The released NB drug significantly improves cancer cell killing in vitro. As a result, the analysis revealed a drug delivery platform by NB to understand the cancer cell targeting strategy.

Background: Investigation for a naturally occurring anti-obesity drug has become the need of society all over the world. Betulinic acid (BA) is a lupane-type pentacyclic triterpene and is sourced from various organisms. This high potential biologically active molecule is reported to have anti-obesity effect. In this study, we report the molecular mechanism of action of BA that underlies anti-obesity activity and also an improved method of its isolation common teak tree. Methods: Mouse pre-adipocyte cells were used to develop hyperlipidemic conditions in vitro. Change in expression of genes associated to adipogenesis was checked using quantitative real-time PCR (qPCR). Co-factor specificity of PPAR gamma was analyzed through immune precipitation and immunoblot. Results: Betulinic acid was found to be effective in reducing the lipid content in 3T3L1 cells. Level of PPAR gamma and LXR alpha was reduced in connection to reduced adipogenesis. Change in steroid responsive co-activators (SRCs) during BA treatment proved that the compound can impart profound change in co-factor selectivity, which is crucial in determining the activity profile of PPAR gamma. BA treatment enhanced the SRC-1 interaction with PPAR gamma while reducing the levels of SRC-3. Conclusion: Present study has proved that betulinic acid, a promising candidate in anti-obesity drug development, has potential in regulating the activity of PPAR gamma through co-factor modulation. Keywords: Adipogenesis, Betulinic acid, NMR, PPAR gamma, Tectona grandis

Recent research has confirmed that Panax ginseng (P. ginseng) has effect on cultured osteoblast of the mouse. In this study we aim to validate the usefulness of tibia quantification by correlating micro-computed tomographic (microCT) images with histology analysis in the aged male rats. A total of thirty – old male WISTAR rats were used and divided into ten 8 weeks rats and ten 112 weeks aged rats with vehicle and ten 112 weeks aged rats with P. ginseng (300 mg/kg/day). Daily oral administration of P. ginseng lasted for 8 weeks. Bone histomorphometric parameters and the trabecular bone microarchitectural properties of tibia were determined by microCT scan. MicroCT analysis showed significantly lower bone mineral density (BMD) and trabecular bone number in the aged group. Ginseng prevented total BMD decrease in the tibia induced by natural aging, which was accompanied by a significant decrease in skeletal remodeling. Furthermore, the aged group with ginseng was found to have a significantly higher osteoblast. In the blood biochemistry results, serum phosphorus, calcium, osteocalcin, T3, and T4 remained unchanged. The present study indicated that P. ginseng might be a potential alternative medicine for the prevention and treatment of natural aging-induced osteoporosis in human. Keywords: Microcomputed tomography, Panax ginseng, Osteoporosis, Bone mineral density

Background: The Panax ginseng plant is used as an herbal medicine. Phytosterols of P. ginseng have inhibitory effects on inflammation-related factors in HepG2 cells. Methods: Phytosterols (e.g., stigmasterol and β-sitosterol) in the roots of P. ginseng grown under various conditions were analyzed using high-performance liquid chromatography. The P. ginseng roots analyzed in this study were collected from three cultivation areas in Korea (i.e., Geumsan, Yeongju, and Jinan) and differed by cultivation year (i.e., 4 years, 5 years, and 6 years) and production process (i.e., straight ginseng, red ginseng, and white ginseng). Results: The concentrations of stigmasterol and β-sitosterol in P. ginseng roots were 2.22–23.04 mg/g and 7.35–59.09 mg/g, respectively. The highest concentrations of stigmasterol and β-sitosterol were in the roots of 6-year-old P. ginseng cultivated in Jinan (82.14 mg/g and 53.23 mg/g, respectively). Conclusion: Six-year-old white ginseng and white ginseng cultivated in Jinan containing stigmasterol and β-sitosterol are potentially a new source of income in agriculture.

Background: Depression is one of the most commonly diagnosed neuropsychiatric diseases, but the underlying mechanism and medicine are not well-known. Although Panax ginseng has been reported to exert protective effects in various neurological studies, little information is available regarding its antidepressant effects. Methods: Here, we examined the antidepressant effect and underlying mechanism of P. ginseng extract (PGE) in a chronic restraint stress (CRS)-induced depression model in mice. Results: Oral administration of PGE for 14 d decreased immobility (depression-like behaviors) time in forced swim and tail suspended tests after CRS induction, which corresponded with attenuation of the levels of serum adrenocorticotropic hormone and corticosterone, as well as attenuated c-Fos expression in the amygdala. PGE enhanced messenger RNA expression level of brain-derived neurotrophic factor but ameliorated microglial activation and neuroinflammation (the level of messenger RNA and protein expression of cyclooxygenase-2 and inducible nitric oxide synthase) in the amygdala of mice after CRS induction. Interestingly, 14-d treatment with celecoxib, a selective cyclooxygenase-2 inhibitor, and Nω-nitro-L-arginine methyl ester hydrochloride, a selective inducible nitric oxide synthase inhibitor, attenuated depression-like behaviors after CRS induction. Additionally, PGE inhibited the upregulation of the nuclear factor erythroid 2 related factor 2 and heme oxygenase-1 pathways. Conclusion: Taken together, our findings suggest that PGE exerts antidepressant-like effect of CRS-induced depression by antineuroinflammatory and antioxidant (nuclear factor erythroid 2 related factor 2/heme oxygenase-1 activation) activities by inhibiting the hypothalamo-pituitary-adrenal axis mechanism. Further studies are needed to evaluate the potential of components of P. ginseng as an alternative treatment of depression, including clinical trial evaluation.

Azima tetracantha is a traditionally used medicinal plant in the Ayurvedic system and folk medicines. The plant has been used for various purposes including inflammatory ailments, arthritis, and various types of toxicities. There are no available reports on its anticancer activity; hence, the study aimed to evaluate its anti-proliferative potential in gastric cancer cells (AGS and KATO III). We observed a dose-dependent decrease in cell proliferation in both the gastric cancer cells; furthermore, a concomitant reduction in the cellular antioxidant status was observed. Pre-treatment with A. tetracantha methanol extract showed a significant reduction in intracellular glutathione levels, and subsequently raised thiobarbituric acid reactive substances. Together with this, a significant increase in the cytochrome c release was noted in A. tetracantha treated cells, alongwith an increase in the expression of pro-apoptotic genes such as BAX, CASP3, CASP7 and APAF1. Furthermore, RTqPCR analysis indicated an increased expression of the anti-apoptotic gene BCL2 in a dose-dependent manner. In addition, to confirm the role of reactive oxygen species in the proliferation inhibition, DCFH-DA-based analysis was carried out, where a dose-dependent increase in ROS levels was observed in these cells. Overall, the study confirms the anticancer efficacy of A. tetracantha leaf methanol extract mediated through the induction of redox imbalance and cytochrome c release.

The leaf of Aurea helianthus (A. helianthus Jinhuakui) is popularly used in China traditional medicine, however, scientific evidence on its antioxidant properties rarely studied. In this study, biological activities of A. helianthus leave’s 80% ethanol extract (AHL) were investigated. The measured total polyphenol and flavonoid content of AHL was 184.24 ± 5.01 mg GAE/g and 102.53 ± 0.98 mg NAR/g. AHL showed the highest α, α-diphenyl-β-picrylhydrazyl (DPPH) and 2,2′-azino-bis-3-ethylbenzo-thiazoline-6-sulfonic acid (ABTS) radical scavenging activities of 98.30 ± 0.18% at 1000 µg/mL. DPPH and ABTS radical scavenging activities significantly increased in a AHL concentration-dependent manner. AHL treatment significantly suppressed the generation of pro-inflammatory mediators, including nitric oxide (NO), in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. AHL demonstrated strong anti-inflammatory activity that reduced NO production in LPS-stimulated RAW 264.7 cells. To test the potential protective effect of AHL, the antioxidant capacity, on the cell growth, viability of a human hepatoma cell (HepG2) and Raw 264.7 cell were investigated. AHL also enhanced cytotoxicity on the proliferation of HepG2 cells and was capable of inhibiting 56% against LPS at 400 µg/mL. The results of this study the potential of AHL as an excellent antioxidant substance for inhibiting inflammatory mediators. Therefore, AHL may be used as a therapeutic approach to various inflammatory diseases.

The present study was carried out to analyze the potential of fungi isolated from the rhizosphere of soybean, brinjal, tomato, and potato plants. The density of fungi varied in the pot soil and rhizosphere after Paecilomyces formosus MD12 treatment. The P. formosus MD12 population was 6.3 ± 0.13 × 104 CFU g−1 in the pot planted with brinjal, and the population increased in the rhizosphere (6.72 ± 0.41 × 104 CFU g−1). P. formosus MD12 was cultured in the production medium, and the supernatant was used for egg inhibition studies on a root-knot nematode parasite, Meloidogyne incognita. It was revealed that maximum egg inhibition (94.7 ± 6.2%) was obtained at 100% concentration of extract. The culture supernatant from P. formosus MD12 affected the development of M. incognita juvenile, and the mortality rate was maximum after 96 h (95 ± 6%). Mortality was reduced when treated with 25%, 50%, and 75% supernatant. At 1 × 107 mL−1 of spore suspension, we found reductions of 71.6 ± 3.3% nematode populations in the soil, 60.7 ± 2.2% from the root, and 63.6 ± 2.4% egg mass compared with the control in the pot experiment. The culture supernatant applied at the 10% level showed a maximum mean reduction of the nematode population in roots (72.4 ± 2.2%), soil (77.9 ± 2.5%), and egg masses (73.2 ± 1.5%), respectively. The presence of P. formosus MD12 in a soil environment could antagonize nematode parasites and improve soil amendment. The P. formosus MD12 strain showed good biocontrol ability against the root-knot nematode, M. incognita, under in vitro and green house experimental condition.

Background: Panax ginseng has been used as Korean medicine for various diseases. It has antioxidant, hypotensive, sedative, analgesic, and endocrine activities. Dammarane-type triterpenes from the plant have various beneficial effects. Methods: A dammarane-type triterpene saponin was isolated from P. ginseng root through chromatography such as repeated column chromatography and medium pressure liquid chromatography. Results and conclusion: New dammarane-type triterpene saponin was isolated for the first time from nature. The structure was elucidated as ginsenoside Rg12 (1) based on spectral data. There may be good materials from P. ginseng for the development of industrial applications such as nutraceutical, pharmaceutical, and cosmeceutical purposes.

Fer1L5 is a dysferlin and myoferlin related protein, which has been predicted to have a role in vesicle trafficking and muscle membrane fusion events. Mutations in dysferlin and otoferlin genes cause heredity diseases: muscular dystrophy and deafness in humans, respectively. Dysferlin is implicated in membrane repair. Myoferlin has a role in myogenesis. In this study, we investigated the role of the Fer1L5 protein during myoblast fusion and membrane repair. To study the functions of Fer1L5 we used confocal microscopy, biochemical fractionation, Western blot analysis and multiphoton laser wounding assay. By immunolabelling, Fer1L5 was detected in vesicular structures. By biochemical fractionation Fer1L5 was observed in low density vesicles. Our studies show that the membranes of Fer1L5 vesicles are non-resistant to non-ionic detergent. Partial co-staining of Fer1L5 with other two ferlin vesicles, respectively, was observed. Fer1L5 expression was highly detected at the fusion sites of two apposed C2C12 myoblast membranes and its expression level gradually increased at D2 and reached a maximum at day 4 before decreasing during further differentiation. Our studies showed that Fer1L5 has fusion defects during myoblast fusion and impaired membrane repair when the C2C12 cultures were incubated with inhibitory Fer1L5 antibodies. In C2C12 cells Fer1L5 vesicles are involved in two stages, the fusion of myoblasts and the formation of large myotubes. Fer1L5 also plays a role in membrane repair.

Abstract Background Adaptive therapy has been enormously improved based on the art of generating adaptive computed tomography (ACT) from planning CT (PCT) and the on-board image used for the patient setup. Exploiting the ACT, this study evaluated the dose delivered to patients with non-small-cell lung cancer (NSCLC) patients treated with stereotactic ablative radiotherapy (SABR) and derived relationship between the delivered dose and the parameters obtained through the evaluation procedure. Methods SABR treatment records of 72 patients with NSCLC who were prescribed a dose of 60 Gy (Dprescribed) to the 95% volume of the planning target volume (PTV) in four fractions were analysed in this retrospective study; 288 ACTs were generated by rigid and deformable registration of a PCT to a cone-beam computed tomography (CBCT) per fraction. Each ACT was sent to the treatment planning system (TPS) and treated as an individual PCT to calculate the dose. Delivered dose to a patient was estimated by averaging four doses calculated from four ACTs per treatment. Through the process, each ACT provided the geometric parameters, such as mean displacement of the deformed PTV voxels (Warpmean) and Dice similarity coefficient (DSC) from deformation vector field, and dosimetric parameters, e.g. difference of homogeneity index (ΔHI, HI defined as (D2%-D98%)/Dprescribed*100) and mean delivered dose to the PTV (Dmean), obtained from the dose statistics in the TPS. Those parameters were analyzed using multiple linear regression and one-way-ANOVA of SPSS® (version 27). Results The prescribed dose was confirmed to be fully delivered to internal target volume (ITV) within maximum difference of 1%, and the difference between the planned and delivered doses to the PTV was agreed within 6% for more than 95% of the ACT cases. Volume changes of the ITV during the treatment course were observed to be minor in comparison of their standard deviations. Multiple linear regression analysis between the obtained parameters and the dose delivered to 95% volume of the PTV (D95%) revealed four PTV parameters [Warpmean, DSC, ΔHI between the PCT and ACT, Dmean] and the PTV D95% to be significantly related with P-values

In recent years, studies have focused on the therapeutic properties of probiotics to eliminate pathogenic microorganisms associated with various diseases. Lactobacilli are important probiotics groups that have been found to possess many health-promoting activities. This study was carried out to isolate LactobacillusreuteriLR12 and L. lactisLL10 from pineapple puree. The invitro analysis to evaluate probiotic characteristics of the isolated bacteria included survival in bile and acid tolerance. The cell-free supernatant of L. reuteri LR12 was effective against various pathogenic bacteria and fungi compared with L. lactisLL10. These two bacterial strains have strong anti-biofilm activity (100%) against Enterococcus faecalis, Staphylococcus aureus, and Bacillus cereus. The bacterial strains exhibited adhesion properties to HT-29 cells (human colorectal adenocarcinoma). These bacteria showed DPPH- (2,2-diphenyl-1-picryl-hydrazyl-hydrate) free radical scavenging activity, scavenging of hydroxyl radical activity, superoxide radical scavenging activity, and reducing power activity in the range of 72% ± 3%to 89.3% ± 1.7%, 64% ± 2.7%to 66.8% ± 1.5%, 59.8% ± 4.1% to 63.8% ± 2.1%, and 60.4% ± 1.8%to 66.1% ± 3.3%, respectively. Pineapple puree was used as the starter culture with milk for 2 days for yogurt preparation. Pineapple puree increased flavor and showed the physicochemical properties of yogurt. The finding of the sensory evaluation revealed no significant change compared with the control, except the appearance of yogurt. These findings show that Lactobacilli and pineapple puree have potential use in various probiotic preparations for the fermentation industry.

The preventive and therapeutic mechanisms in multiple sclerosis are not clearly understood. We investigated whether Hyungbangpaedok-san (HBPDS), a traditional herbal medicine, has a beneficial effect in experimental autoimmune encephalomyelitis (EAE) mice immunized with myelin oligodendrocyte glycoprotein peptide (MOG 35-55). Onset-treatment with 4 types of HBPDS (extracted using distilled water and 30%/70%/100% ethanol as the solvent) alleviated neurological signs, and HBPDS extracted within 30% ethanol (henceforth called HBPDS) was more effective. Onset-treatment with HBPDS reduced demyelination and the recruitment/infiltration and activation of microglia/macrophages in the spinal cord of EAE mice, which corresponded to the reduced mRNA expression of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β), iNOS, and chemokines (MCP-1, MIP-1α, and RANTES) in the spinal cord. Onset-treatment with HBPDS inhibited changes in the components of the blood-brain barrier such as astrocytes, adhesion molecules (ICAM-1 and VCAM-1), and junctional molecules (claudin-3, claudin-5, and zona occludens-1) in the spinal cord of EAE mice. Onset-treatment with HBPDS reduced the elevated population of CD4+, CD4+/IFN-γ+, and CD4+/IL-17+ T cells in the spinal cord of EAE mice but it further increased the elevated population of CD4+/CD25+/Foxp3+ and CD4+/Foxp3+/Helios+ T cells. Pre-, onset-, post-, but not peak-treatment, with HBPDS had a beneficial effect on behavioral impairment in EAE mice. Taken together, HBPDS could alleviate the development/progression of EAE by regulating the recruitment/infiltration and activation of microglia and peripheral immune cells (macrophages, Th1, Th17, and Treg cells) in the spinal cord. These findings could help to develop protective strategies using HBPDS in the treatment of autoimmune disorders including multiple sclerosis.

Abstract Background Thymic epithelial tumors (TET) are rare malignancies and lack well‐defined biomarkers for neoadjuvant therapy. This study aimed to evaluate the clinical utility of artificial intelligence (AI)‐powered tumor‐infiltrating lymphocyte (TIL) analysis in TET. Methods Patients initially diagnosed with unresectable thymoma or thymic carcinoma who underwent neoadjuvant therapy between January 2004 and December 2021 formed our study population. Hematoxylin and eosin‐stained sections from the initial biopsy and surgery were analyzed using an AI‐powered spatial TIL analyzer. Intratumoral TIL (iTIL) and stromal TIL (sTIL) were quantified and their immune phenotype (IP) was identified. Results Thirty‐five patients were included in this study. The proportion of patients with partial response to neoadjuvant therapy was higher in the group with nondesert IP in preneoadjuvant biopsy (63.6% vs. 17.6%, p = 0.038). A significant increase in both iTIL (median 22.18/mm2 vs. 340.69/mm2, p 147/mm2) exhibited longer disease‐free survival (median, 29 months vs. 12 months, p = 0.009) and overall survival (OS) (median, 62 months vs. 45 months, p = 0.002). Patients with higher sTIL (>232.1/mm2) exhibited longer OS (median 62 months vs. 30 months, p = 0.021). Conclusions Nondesert IP in initial biopsy was associated with a better response to neoadjuvant therapy. Increased infiltration of both iTIL and sTIL in surgical specimens were associated with longer OS in patients with TET who underwent resection followed by neoadjuvant therapy.

Abstract Purpose The aim of this study was to evaluate the treatment outcomes and potential dose-response relationship of stereotactic body radiation therapy (SBRT) for pulmonary metastasis of sarcoma. Materials and methods A retrospective review of 39 patients and 71 lesions treated with SBRT from two institutions was performed. The patients had oligometastatic or oligoprogressive disease, or were receiving palliation. Doses of 20–60 Gy were delivered in 1–5 fractions. The local control per tumor (LCpT) was evaluated according to the biologically effective dose with an α/β ratio of 10 (BED10) of the prescribed dose (BED10 ≥ 100 Gy vs. BED10

Background: Noninvasive cardiac radioablation is reported to be effective and safe for the treatment of ventricular tachycardia (VT). Objective: This study aimed to analyze the acute and long-term effects of VT radioablation. Methods: Patients with intractable VT or premature ventricular contraction (PVC)–induced cardiomyopathy were included in this study and treated using a single-fraction 25-Gy dose of cardiac radioablation. To quantitatively analyze the acute response after treatment, continuous electrocardiography monitoring was performed from 24 hours before to 48 hours after irradiation and at the 1-month follow-up. Long-term clinical safety and efficacy were assessed 1-year follow-up. Results: From 2019 to 2020, 6 patients were treated with radioablation for ischemic VT (n = 3), nonischemic VT (n = 2), or PVC-induced cardiomyopathy (n = 1). In the short-term assessment, the total burden of ventricular beats decreased by 49% within 24 hours after radioablation and further decreased by 70% at 1 month. The VT component decreased earlier and more dramatically than the PVC component (decreased by 91% and 57% at 1 month, respectively). In the long-term assessment, 5 patients showed complete (n = 3) or partial (n = 2) remission of ventricular arrhythmias. One patient showed recurrence at 10 months, which was successfully suppressed with medical treatment. The posttreatment PVC coupling interval was prolonged (+38 ms at 1 month). Ischemic VT burden decreased more markedly than nonischemic VT burden after radioablation. Conclusion: In this small case series of 6 patients, without a comparison group, cardiac radioablation appeared to decrease the intractable VT burden. A therapeutic effect was apparent within 1–2 days after treatment but was variable by etiology of cardiomyopathy.

Introduction Low-dose radiation therapy (LDRT) for osteoarthritis (OA) has been performed for several decades. However, supporting evidence from randomised studies using modern methodologies is lacking, and a recently published randomised study failed to show the significant benefit of LDRT. The presented trial aims to evaluate the efficacy and safety of LDRT for patients with knee OA.Methods and analysis This prospective, multicentre, randomised trial will be conducted in the Republic of Korea. A total of 114 participants will be randomly assigned (1:1:1) to receive sham irradiation, 0.3 Gy/6 fractions of LDRT or 3 Gy/6 fractions of LDRT. Key inclusion criteria are primary knee OA with Kellgren-Lawrence grade 2–3 and visual analogue scale 50–90 when walking at the baseline. The primary endpoint is the rate of responders at 4 months after LDRT according to the OARSI-OMERACT criteria. Concomitant use of analgesics is prohibited until the primary efficacy evaluation is scheduled.Ethics and dissemination Currently, approval from the Ministry of Food and Drug Safety of the Republic of Korea and the institutional review board of each participating hospital has been obtained. Patient enrolment began in October 2022 and is ongoing at three participating sites. The results will be disseminated to academic audiences and the public via publication in an international peer-reviewed journal and presentation at conferences. This trial will provide valuable information on the safety and efficacy of LDRT for patients with knee OA.Trial registration number NCT05562271.

IntroductionThe dosimetric factors of radiotherapy have an acute impact on the host immune system during chemoradiotherapy (CRT) in locally advanced non-small cell lung cancer (NSCLC). However, even after CRT, a substantial number of patients remain immunosuppressed with delayed lymphopenia. Therefore, we aimed to evaluate clinical and dose-volumetric predictors of delayed lymphopenia after CRT in locally advanced NSCLC.Materials and methodsWe retrospectively reviewed 272 patients with locally advanced NSCLC who received definitive CRT from January 2012 to August 2020. Differential blood count data, including serum albumin values, were obtained at baseline, during and at first follow up after CRT. Acute and delayed lymphopenia events were defined as grade III/IV lymphopenia developed during or 4-12 weeks after CRT completion, which accounted for 84% and 10% of cases, respectively. Dose-volume histogram parameters for planned target volume, whole body, heart, lung, great vessels, spleen, esophagus and thoracic vertebral bodies were evaluated.ResultsMultivariate analysis revealed that patients with delayed lymphopenia were associated with inferior overall survival (HR 2.53, P = 0.001) and progression-free survival (HR 1.98, P = 0.006). However, there was no significant survival difference between groups stratified by acute lymphopenia. On multivariable logistic regression models, lung V5, baseline ALC, during-CRT ALC, and albumin nadir were significant predictors for delayed lymphopenia. Furthermore, the nomogram for delayed lymphopenia based on these variables had good discrimination (area under the curve, 0.905).ConclusionsIn this study, we investigated the prognostic significance of delayed lymphopenia and identified clinico-dosimetric parameters to predict delayed lymphopenia.

Although Fanconi anemia patients accompany a high risk of multiple cancers, radiation therapy on these patients has been carried out only in limited cases due to the concern for radiation toxicity that stems from their susceptibility to radiation. We report a case of a 28-year-old female patient diagnosed as synchronous esophageal and tongue cancer, and underwent two cycles of radiation therapy, inevitably in the condition of coronavirus disease 2019 infection. She received radiation therapy of 30 Gy to esophageal mass with neoadjuvant aim in her first-round radiation therapy, and later received 27 Gy to tongue cancer surgical bed with adjuvant aim in her second-round radiation therapy. With no further treatment, she has been maintaining no evidence of disease state for 7 months. Managing Fanconi anemia patients with multiple cancers using radiation therapy is feasible, in which cases a dose de-escalation may be important considering the radiation toxicity and possible future re-treatment. [ABSTRACT FROM AUTHOR]

Purpose: Pulmonary sarcomatoid carcinoma (PSC) is recognized for its aggressiveness and poor prognosis. The role of radical radiotherapy in PSC remains uncertain due to its scarcity and limited data. In the absence of an effective systemic agent, this study aims to explore the possibility of cure and to investigate potential prognostic factors and treatment outcomes. Materials and Methods: From January 2005 to December 2021, 149 PSC patients were identified. Among 62 patients who received radiotherapy for lung lesions, 25 who underwent palliative radiotherapy and 16 who underwent surgery were excluded. Results: The median patient age was 71 years. The majority were male, and 17 patients (81.0%) were diagnosed at an advanced stage. After radical radiotherapy, distant metastasis (47.6%) was the most common site of failure, while the local recurrence rate was quite low (9.5%). Eventually, five patients (26.3%) demonstrated either a partial response or complete remission, including three complete remissions with durable responses. The median progression-free survival (PFS) and overall survival were 4.6 months and 7.9 months, respectively. Univariate and multivariate analyses revealed that a tumor size >5 cm was associated with a worse prognosis (p = 0.045), while a radiation dose >58 GyEQD2 was significantly associated with better PFS (p = 0.038). Conclusion: This study demonstrates clinical outcomes after radical radiotherapy in managing PSC, suggesting tumor size and radiation dose could be a predictor of a systemic response. Given the known bad prognosis but complete remission could be achieved in certain subgroups, future research should explore the potential strategies using radical radiotherapy for this challenging patient population. [ABSTRACT FROM AUTHOR]

Despite conventionally applied postoperative radiotherapy (PORT) in pathological N2 (pN2) stage non-small cell lung cancer (NSCLC) considering high locoregional recurrence, its survival benefit has been a continuous topic of debate. Although several randomized clinical trials have been conducted, many of them have been withdrawn or analyzed without statistical significance due to slow accrual, making it difficult to determine the efficacy of PORT. Recently, the results of large-scale randomized clinical trials have been published, which showed some improvement in disease-free survival with PORT, but finally had no impact on overall survival. Based on these results, it was expected that the debate over PORT in pN2 patients with NSCLC would come to an end. However, since pN2 patients have different clinicopathologic features, it has become more important to carefully select the patient population who will benefit from PORT. In addition, given the development of systemic treatments such as molecular-targeted therapy and immunotherapy, it is crucial to evaluate whether there is any benefit to PORT in the midst of these recent changes. Therefore, determining the optimal treatment approach for NSCLC pN2 patients remains a complex issue that requires further research and evaluation. [ABSTRACT FROM AUTHOR]