1.Isoliquiritigenin Induces Apoptosis via ROS-Mediated Inhibition of p38/mTOR/STAT3 Pathway in Human Melanoma Cells
Mi Jeong KWON ; Pawan Kumar RAUT ; Jeong-Hoon JANG ; Kyung-Soo CHUN
Biomolecules & Therapeutics 2025;33(2):378-387
Isoliquiritigenin (ISL), a phenolic compound derived from licorice, exhibits various biological activities, including anti-inflammatory, anti-viral, anti-tumor, and antioxidant effects. However, the molecular mechanisms underlying its anti-cancer effects are not well understood in SK-MEL-28 melanoma cells. Melanoma, a highly aggressive and treatment-resistant cancer, remains a significant health challenge. This study investigates the anti-cancer effects of ISL, focusing on identifying reactive oxygen species (ROS)-mediated apoptosis mechanisms on SK-MEL-28 melanoma cells. Our results show that ISL treatment induces apoptosis in SK-MEL-28 cells, as evidenced by the cleavage of caspase-9, -7, -3, and PARP. ISL increased Bax expression, decreased Bcl-2 expression, and promoted cytochrome C release into the cytosol. ISL also reduced the expression of cell cycle markers, including cyclin D1, D3, and survivin. Notably, ISL treatment markedly increased intracellular ROS levels and pretreatment with N-acetyl cysteine, a ROS scavenger, abrogated the ISL-induced inhibition of the p38/mTOR/STAT3 pathway and prevented apoptosis.Moreover, ISL significantly diminished the constitutive phosphorylation of mTOR and STAT3 in SK-MEL-28 cells by blocking the phosphorylation of p38 MAPK, an upstream kinase of mTOR. Pharmacological inhibition of mTOR attenuated the STAT3 signaling, indicating that mTOR acts as an upstream kinase of STAT3 in these cells. Collectively, these findings demonstrate that ISL inhibits SK-MEL-28 cell growth by downregulating cell survival proteins and inducing apoptosis through ROS generation.
2.Isoliquiritigenin Induces Apoptosis via ROS-Mediated Inhibition of p38/mTOR/STAT3 Pathway in Human Melanoma Cells
Mi Jeong KWON ; Pawan Kumar RAUT ; Jeong-Hoon JANG ; Kyung-Soo CHUN
Biomolecules & Therapeutics 2025;33(2):378-387
Isoliquiritigenin (ISL), a phenolic compound derived from licorice, exhibits various biological activities, including anti-inflammatory, anti-viral, anti-tumor, and antioxidant effects. However, the molecular mechanisms underlying its anti-cancer effects are not well understood in SK-MEL-28 melanoma cells. Melanoma, a highly aggressive and treatment-resistant cancer, remains a significant health challenge. This study investigates the anti-cancer effects of ISL, focusing on identifying reactive oxygen species (ROS)-mediated apoptosis mechanisms on SK-MEL-28 melanoma cells. Our results show that ISL treatment induces apoptosis in SK-MEL-28 cells, as evidenced by the cleavage of caspase-9, -7, -3, and PARP. ISL increased Bax expression, decreased Bcl-2 expression, and promoted cytochrome C release into the cytosol. ISL also reduced the expression of cell cycle markers, including cyclin D1, D3, and survivin. Notably, ISL treatment markedly increased intracellular ROS levels and pretreatment with N-acetyl cysteine, a ROS scavenger, abrogated the ISL-induced inhibition of the p38/mTOR/STAT3 pathway and prevented apoptosis.Moreover, ISL significantly diminished the constitutive phosphorylation of mTOR and STAT3 in SK-MEL-28 cells by blocking the phosphorylation of p38 MAPK, an upstream kinase of mTOR. Pharmacological inhibition of mTOR attenuated the STAT3 signaling, indicating that mTOR acts as an upstream kinase of STAT3 in these cells. Collectively, these findings demonstrate that ISL inhibits SK-MEL-28 cell growth by downregulating cell survival proteins and inducing apoptosis through ROS generation.
3.Isoliquiritigenin Induces Apoptosis via ROS-Mediated Inhibition of p38/mTOR/STAT3 Pathway in Human Melanoma Cells
Mi Jeong KWON ; Pawan Kumar RAUT ; Jeong-Hoon JANG ; Kyung-Soo CHUN
Biomolecules & Therapeutics 2025;33(2):378-387
Isoliquiritigenin (ISL), a phenolic compound derived from licorice, exhibits various biological activities, including anti-inflammatory, anti-viral, anti-tumor, and antioxidant effects. However, the molecular mechanisms underlying its anti-cancer effects are not well understood in SK-MEL-28 melanoma cells. Melanoma, a highly aggressive and treatment-resistant cancer, remains a significant health challenge. This study investigates the anti-cancer effects of ISL, focusing on identifying reactive oxygen species (ROS)-mediated apoptosis mechanisms on SK-MEL-28 melanoma cells. Our results show that ISL treatment induces apoptosis in SK-MEL-28 cells, as evidenced by the cleavage of caspase-9, -7, -3, and PARP. ISL increased Bax expression, decreased Bcl-2 expression, and promoted cytochrome C release into the cytosol. ISL also reduced the expression of cell cycle markers, including cyclin D1, D3, and survivin. Notably, ISL treatment markedly increased intracellular ROS levels and pretreatment with N-acetyl cysteine, a ROS scavenger, abrogated the ISL-induced inhibition of the p38/mTOR/STAT3 pathway and prevented apoptosis.Moreover, ISL significantly diminished the constitutive phosphorylation of mTOR and STAT3 in SK-MEL-28 cells by blocking the phosphorylation of p38 MAPK, an upstream kinase of mTOR. Pharmacological inhibition of mTOR attenuated the STAT3 signaling, indicating that mTOR acts as an upstream kinase of STAT3 in these cells. Collectively, these findings demonstrate that ISL inhibits SK-MEL-28 cell growth by downregulating cell survival proteins and inducing apoptosis through ROS generation.
4.Laparoscopic subtotal cholecystectomy in difficult gallbladder: Our experience in a tertiary care center
Kulbhushan HALDENIYA ; Krishna S. R. ; Annagiri RAGHAVENDRA ; Pawan Kumar SINGH
Annals of Hepato-Biliary-Pancreatic Surgery 2024;28(2):214-219
Background:
s/Aims: Open cholecystectomy is becoming obsolete and laparoscopic cholecystectomy has become the treatment of choice in gallstone diseases. Difficult gallbladders are encountered whenever there is a frozen calot’s triangle, obliterated cystic plate, or both. Rather than converting to open procedure, there has been a growing preference for laparoscopic subtotal cholecystectomy (LSC) during difficult gallbladders. This study aimed to assess the advantages, indications, and viability of LSC in difficult gallbladders.
Methods:
The study included patients undergoing laparoscopic cholecystectomy in NIMS Hospital, Jaipur, from January 2021 to January 2023. Data of the patients who underwent LSC for difficult gallbladders included demographics, comorbidities, operative time, conversion to open cholecystectomy, length of hospital stay, and complications. LSC was classified into three types depending on the part of the gallbladder remnant.
Results:
A total of 728 patients underwent laparoscopic cholecystectomy. Among them, 41 patients (5.6%) were attempted for LSC.However, one patient was converted to an open procedure and the rest 40 underwent LSC. LSC was divided into 3 types, 4 patients underwent LSC type I, 34 patients underwent type II, and 2 patients type III. The average operating time and postoperative length of hospital stay were 86.2 minutes and 2.1 days, respectively. Two patients had surgical site infection. No patient had a bile leak and none required intensive care unit care.
Conclusions
LSC is a safe and feasible option for use in difficult gallbladders.
5.Efficacy of Bacillus Calmette-Guérin in Cancer Prevention and Its Putative Mechanisms
Sakshi GUPTA ; Saurabh YADAV ; Pawan KUMAR
Journal of Cancer Prevention 2024;29(1):6-15
Bacillus Calmette-Guérin (BCG) is an attenuated strain of Mycobacterium bovis. Although it was developed as a prophylactic vaccine against tuberculosis (TB), researchers have also evaluated it for preventing cancer development or progression. These studies were inspired by the available data regarding the protective effects of microbial infection against cancers and an inverse relationship between TB and cancer mortality. Initial studies demonstrated the efficacy of BCG in preventing leukemia, melanoma and a few other cancers. However, mixed results were observed in later studies. Importantly, these studies have led to the successful use of BCG in the tertiary prevention of non-muscle invasive bladder cancer, wherein BCG therapy has been found to be more effective than chemotherapy. Moreover, in a recently published 60-year follow-up study, childhood BCG vaccination has been found to significantly prevent lung cancer development. In the present manuscript, we reviewed the studies evaluating the efficacy of BCG in cancer prevention and discussed its putative mechanisms. Also, we sought to explain the mixed results of BCG efficacy in preventing different cancers.
7.Aedes aegypti container preference for oviposition and its possible implications for dengue vector surveillance in Delhi, India
Pooja PRASAD ; Suman LATA ; Sanjeev Kumar GUPTA ; Pawan KUMAR ; Rekha SAXENA ; Deepak Kumar ARYA ; Himmat SINGH
Epidemiology and Health 2023;45(1):e2023073-
OBJECTIVES:
Dengue is a mosquito-borne viral disease globally transmitted by Aedes aegypti. The most effective method to prevent the transmission of the disease is proficient vector control. Understanding the breeding behaviour of the responsible vectors is very pertinent in this regard; therefore, the present study was conducted to understand Ae. aegypti behaviour regarding the selection of containers for oviposition in the megacity of Delhi.
METHODS:
A household survey in different localities within Delhi was carried out during 2018-2019. All available containers were inspected for the presence of immature Ae. aegypti. In entomological surveillance, the ovipositional preference of Aedes was computed using the breeding preference ratio, container index in the field, and laboratory settings, and associations of dengue cases with monthly variation in environmental factors and container type were also calculated.
RESULTS:
The household larval survey in 40 localities showed that 40% of 27,776 water-holding containers in 3,400 houses were plastic, followed by overhead tanks (26.2%), and coolers (12.1%). The most preferred breeding habitat was clay pots (9.3%), followed by metallic containers (8.5%) and solid waste (7.1%). A laboratory-based study showed that Aedes preferred clay containers (81.8%) over 4 other types of containers (plastic, paper, metal, and glass).
CONCLUSIONS
The present study provides a rationale for using clay containers as a possible surveillance tool (ovitraps) or as a vector control tool. This information might aid researchers in developing novel traps and targeting preferred containers for larval control activities during transmission and non-transmission seasons.
8.Evaluation of early versus delayed laparoscopic cholecystectomy in acute calculous cholecystitis: a prospective, randomized study
Gaurav GUPTA ; Ajay SHAHBAJ ; Dharmendra Kumar PIPAL ; Pawan SAINI ; Vijay VERMA ; Sangeeta GUPTA ; Vibha RANI ; Seema YADAV
Journal of Minimally Invasive Surgery 2022;25(4):139-144
Purpose:
Uncertainty exists about whether early laparoscopic cholecystectomy (LC) is an appropriate surgical treatment for acute calculous cholecystitis. This study aimed to compare early vs. late LC for acute calculous cholecystitis regarding intraoperative difficulty and postoperative outcomes.
Methods:
This was a prospective randomized study carried out between December 2015 and June 2017; 60 patients with acute calculous cholecystitis were divided into two groups (early and delayed groups), each comprising 30 patients. Thirty patients treated with LC within 3 to 5 days of arrival at the hospital were assigned to the early group. The other 30 patients were placed in the delayed group, first treated conservatively, and followed by LC 3 to 6 weeks later.
Results:
The conversion rates in both groups were 6.7% and 0%, respectively (p = 0.143). The operating time was 56.67 ± 11.70 minutes in the early group and 75.67 ± 20.52 minutes in the delayed group (p = 0.001), and both groups observed equal levels of postoperative complications. Early LC patients, on the other hand, required much fewer postoperative hospital stay (3.40 ± 1.99 vs. 6.27 ± 2.90 days, p = 0.006).
Conclusion
Considering shorter operative time and hospital stay without significant increase of open conversion rates, early LC might have benefits over late LC.
9.Delayed Spontaneous Thrombosis of Neglected Direct Carotid-Cavernous Fistula: A Case Report
Sarbesh TIWARI ; Pawan Kumar GARG ; Pushpinder Singh KHERA ; Santosh Babu K.B ; Taruna YADAV ; Binit SUREKA
Neurointervention 2020;15(2):96-100
Direct carotid-cavernous fistula (CCF) refers to direct communication between the cavernous portion of the internal carotid artery (ICA) and the cavernous sinus due to rent in the ICA, most commonly secondary to trauma. These are generally high-flow fistula and rarely resolve spontaneously. We report a case of a young male who developed features of direct CCF after trauma, was denied any treatment for 4 years, and then presented with spontaneous thrombosis of the fistula and a residual large pseudoaneurysm of the cavernous segment of the right ICA, which was subsequently managed with parent vessel occlusion.
10.Finger pulp reconstruction with thenar flap: Aesthetic and functional outcome
Kumar Ranjit SAHU ; Chandra Prakash KALA ; Kumar Pawan DIXIT ; Shankar Sourabh CHAKRABORTY ; Suresh K ; Deepti KATROLIA
Chinese Journal of Traumatology 2020;23(5):307-310
Purpose::Fingertip injuries are common in industrial production activities as well as in domestic work. Loss of pulp hampers daily life activities. Functional and aesthetic aspects are important in fingertip reconstruction. The bone is usually exposed along with soft tissue loss. Therefore to reconstruct the pulp flap with adequate bulk is required.Methods::We reported a case series of 12 patients with the injury over the volar aspect of distal phalanx of the index or middle finger. In all cases, laterally based thenar flap was chosen. The flap donor site was closed primarily in most of cases, while 4 patients required skin graft. The flap was detached between 2-3 weeks. Functional assessment was done using static and dynamic 2-point discrimination and range of motion at each joint. The aesthetic outcome was assessed through questionnaire. The results were analyzed using the unpaired t-test (SPSS version 21). Results::Partial necrosis occurred in 2 cases while rest of flaps survived successfully. Static 2-point discrimination ranged from 6-10 mm, mean 8.6 mm; and dynamic 2-point discrimination ranged from 8-10 mm, mean 8.9 mm. The mean satisfaction score was (4.0 ± 0.55).Conclusion::Thenar flap is a good choice for reconstruction of the finger pulp as it provides the bulk with good functional and aesthetic outcome.

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