Oral squamous cell carcinoma (OSCC) progresses from preneoplastic precursors via genetic and epigenetic alterations. Previous studies have focused on the treatment of terminally developed OSCC. However, the role of epigenetic regulators as therapeutic targets during the transition from preneoplastic precursors to OSCC has not been well studied. Our study identified lysine-specific demethylase 1 (LSD1) as a crucial promoter of OSCC, demonstrating that its knockout or pharmacological inhibition in mice reversed OSCC preneoplasia. LSD1 inhibition by SP2509 disrupted cell cycle, reduced immunosuppression, and enhanced CD4+ and CD8+ T-cell infiltration. In a feline model of spontaneous OSCC, a clinical LSD1 inhibitor (Seclidemstat or SP2577) was found to be safe and effectively inhibit the STAT3 network. Mechanistic studies revealed that LSD1 drives OSCC progression through STAT3 signaling, which is regulated by phosphorylation of the cell cycle mediator CDK7 and immunosuppressive CTLA4. Notably, LSD1 inhibition reduced the phosphorylation of CDK7 at Tyr170 and eIF4B at Ser422, offering insights into a novel mechanism by which LSD1 regulates the preneoplastic-to-OSCC transition. This study provides a deeper understanding of OSCC progression and highlights LSD1 as a potential therapeutic target for controlling OSCC progression from preneoplastic lesions.
STAT3 Transcription Factor/metabolism* ; Animals ; Histone Demethylases/genetics* ; Phosphorylation ; Mouth Neoplasms/immunology* ; Mice ; Carcinoma, Squamous Cell/immunology* ; Disease Progression ; Cyclin-Dependent Kinase-Activating Kinase ; Precancerous Conditions/metabolism* ; Humans ; Cyclin-Dependent Kinases/metabolism* ; Disease Models, Animal

OBJECTIVE: In Pakistan, traditional medicines are an important component of the medical system, with numerous varieties and great demands. However, due to the scattered resources and the lack of systematic collection and collation, adulteration of traditional Pakistani medicine (TPM) is common, which severely affects the safety of their medicinal use and the import and export trades. Therefore, it is urgent to systematically organize and unify the management of TPM and establish a set of standards and operable methods for the identification of TPM. METHODS: We collected and organized the information on 128 TPMs with regard to their medicinal parts, efficacy, usage, and genetic material, based on Pakistan Hamdard Pharmacopoeia of Eastern Medicine: Pharmaceutical Codex. The genetic information of TPM is summarized from national center for biotechnology information (NCBI) and global pharmacopoeia genome database (GPGD). Furthermore, we utilized bioinformatics technology to supplement the chloroplast genome (cp-genome) data of 12 TPMs. To build the web server, we used the Linux + Apache + MySQL + PHP (LAMP) system and constructed the webpage on a PHP: Hypertext Preprocessor (PHP) model view controller (MVC) framework. RESULTS: We constructed a new genomic database, the traditional Pakistani medicine genomic database (TPMGD). This database comprises five entries, namely homepage, medicinal species, species identification, basic local alignment search tool (BLAST), and download. Currently, TPMGD contains basic profiles of 128 TPMs and genetic information of 102 TPMs, including 140 cytochrome c oxidase subunit I (COI) sequences and 119 mitochondrial genome sequences from Bombyx mori, 1 396 internal transcribed spacer 2 (ITS2) sequences and 1 074 intergenic region (psbA-trnH) sequences specific to 92 and 83 plant species, respectively. Additionally, TPMGD includes 199 cp-genome sequences of 82 TPMs. CONCLUSION TPMGD is a multifunctional database that integrates species description, functional information inquiry, genetic information storage, molecular identification of TPM, etc. The database not only provides convenience for TPM information queries but also establishes the scientific basis for the medication safety, species identification, and resource protection of TPM.

Purpose: This study aimed to determine the effect of tumor resection on dysbiosis of the intestinal microbiota in patients with right-sided colon cancer. Methods: This study utilized a longitudinal design to explore the outcomes of patients diagnosed with right-sided colon cancer who underwent surgical resection at Dr. M. Djamil General Hospital from July to December 2023. We excluded patients with a documented history of comorbidities, specifically those affecting the digestive system. To compare the microbiota (genus and phylum) between patients with right-sided colon cancer and the control group, we conducted bivariate analyses using the independent t-test or Mann-Whitney test. Furthermore, we employed the dependent t-test or Wilcoxon test to assess changes in the dysbiosis of the microbiota (genus and phylum) before and after resection. A P-value of <0.05 was considered statistically significant. Results: This study included a total of 21 patients diagnosed with right-sided colon cancer. In the control group, Bacteroidetes constituted the highest proportion of intestinal microbiota, accounting for 56.34%. Prior to tumor resection, the intestinal microbiota of patients exhibited Proteobacteria as the predominant phylum, representing 52.97%. Following tumor resection, Bacteroidetes remained the most prevalent, comprising 50.9% of the intestinal microbiota. Significant variations in the levels of Proteobacteria, Verrucomicrobia, and Cyanobacteria/Chloroplast were observed in the intestinal microbiota of patients with right-sided colorectal cancer before and after tumor excision (all P=0.001). Conclusion The microbiome of patients with right-sided colorectal cancer differed significantly from that of the control group. However, following tumor resection, the microbiome composition of these patients became more similar to that observed in the control group.

Purpose: This study aimed to determine the effect of tumor resection on dysbiosis of the intestinal microbiota in patients with right-sided colon cancer. Methods: This study utilized a longitudinal design to explore the outcomes of patients diagnosed with right-sided colon cancer who underwent surgical resection at Dr. M. Djamil General Hospital from July to December 2023. We excluded patients with a documented history of comorbidities, specifically those affecting the digestive system. To compare the microbiota (genus and phylum) between patients with right-sided colon cancer and the control group, we conducted bivariate analyses using the independent t-test or Mann-Whitney test. Furthermore, we employed the dependent t-test or Wilcoxon test to assess changes in the dysbiosis of the microbiota (genus and phylum) before and after resection. A P-value of <0.05 was considered statistically significant. Results: This study included a total of 21 patients diagnosed with right-sided colon cancer. In the control group, Bacteroidetes constituted the highest proportion of intestinal microbiota, accounting for 56.34%. Prior to tumor resection, the intestinal microbiota of patients exhibited Proteobacteria as the predominant phylum, representing 52.97%. Following tumor resection, Bacteroidetes remained the most prevalent, comprising 50.9% of the intestinal microbiota. Significant variations in the levels of Proteobacteria, Verrucomicrobia, and Cyanobacteria/Chloroplast were observed in the intestinal microbiota of patients with right-sided colorectal cancer before and after tumor excision (all P=0.001). Conclusion The microbiome of patients with right-sided colorectal cancer differed significantly from that of the control group. However, following tumor resection, the microbiome composition of these patients became more similar to that observed in the control group.

The pharmaceutical research sector is highly interested in oral gastro-retentive dose formulations. The significance of gastro-retentive drug delivery systems (GRDDS) has grown as these systems enhance patient compliance and improve the therapeutic indices of medications. Various technical advancements in the design and production of gastro-retentive dosage forms can overcome physiological limitations, such as short gastric retention time and fluctuations in stomach emptying. Medications with shorter half-lives, instability or poor solubility at alkaline pH, or inadequate absorption in the lower gastrointestinal tract can greatly benefit from GRDDS. To achieve the desired retention period and release pattern, these systems can be developed using a range of innovative methods, including magnetic, bioadhesive, expandable, and floating systems. The use of GRDDS for oral drug administration has significantly increased in recent years, with innovative design strategies—such as the widely used floating drug delivery system—playing a major role. GRDDS offer several advantages, including the ability to provide drugs with a narrow absorption window, improved pharmacological effects, reduced dosing frequency, enhanced bioavailability, and prolonged drug residence in the stomach for local effects such as the treatment of peptic ulcer disease. This study provides a brief introduction to gastro-retentive drug delivery, covering its necessity, advantages, disadvantages, influencing factors, approaches, and applications.

Background/Aims: Amitriptyline is prescribed off-label for irritable bowel syndrome (IBS). We conducted a meta-analysis to assess its efficacy. Methods: A systematic literature review was conducted until November 10, 2023, using MEDLINE, Embase, Cochrane Library, and Web of Science to study the efficacy of amitriptyline in patients with IBS. We included all randomized controlled trials that compared amitriptyline to placebo. Revised Cochrane risk-of-bias tool was used to assess the quality of studies. Meta-analyses were performed using a bivariate random-effects model. Statistical analyses were performed using R Software 4.2.3 and heterogeneity was assessed with I 2 statistics. Results: Seven trials were included with 796 patients (61% female). Amitriptyline was associated with better treatment response (OR, 5.30; 95% CI, 2.47 to 11.39; P < 0.001), reduced Irritable Bowel Syndrome Symptom Severity Scores (MD, –50.72; 95% CI, –94.23 to –7.20; P = 0.020) and improved diarrhea (OR, 10.55; 95% CI, 2.90 to 38.41; P < 0.001). No significant difference between the 2 groups regarding the adverse effects was observed. Three trials showed an overall low risk of bias, 2 trials showed an overall high risk of bias due to randomization and missing data, and 2 trials had some concerns regarding missing data. Conclusions Amitriptyline was found to be well-tolerated and effective in treating IBS compared to placebo. These findings support the use of amitriptyline for the management of IBS, particularly among patients with the IBS diarrhea subtype. Future research should focus on the dose-dependent effects of amitriptyline in IBS to better guide clinicians in personalized titration regimens.

Purpose: This study aimed to determine the effect of tumor resection on dysbiosis of the intestinal microbiota in patients with right-sided colon cancer. Methods: This study utilized a longitudinal design to explore the outcomes of patients diagnosed with right-sided colon cancer who underwent surgical resection at Dr. M. Djamil General Hospital from July to December 2023. We excluded patients with a documented history of comorbidities, specifically those affecting the digestive system. To compare the microbiota (genus and phylum) between patients with right-sided colon cancer and the control group, we conducted bivariate analyses using the independent t-test or Mann-Whitney test. Furthermore, we employed the dependent t-test or Wilcoxon test to assess changes in the dysbiosis of the microbiota (genus and phylum) before and after resection. A P-value of <0.05 was considered statistically significant. Results: This study included a total of 21 patients diagnosed with right-sided colon cancer. In the control group, Bacteroidetes constituted the highest proportion of intestinal microbiota, accounting for 56.34%. Prior to tumor resection, the intestinal microbiota of patients exhibited Proteobacteria as the predominant phylum, representing 52.97%. Following tumor resection, Bacteroidetes remained the most prevalent, comprising 50.9% of the intestinal microbiota. Significant variations in the levels of Proteobacteria, Verrucomicrobia, and Cyanobacteria/Chloroplast were observed in the intestinal microbiota of patients with right-sided colorectal cancer before and after tumor excision (all P=0.001). Conclusion The microbiome of patients with right-sided colorectal cancer differed significantly from that of the control group. However, following tumor resection, the microbiome composition of these patients became more similar to that observed in the control group.

Background/Aims: Amitriptyline is prescribed off-label for irritable bowel syndrome (IBS). We conducted a meta-analysis to assess its efficacy. Methods: A systematic literature review was conducted until November 10, 2023, using MEDLINE, Embase, Cochrane Library, and Web of Science to study the efficacy of amitriptyline in patients with IBS. We included all randomized controlled trials that compared amitriptyline to placebo. Revised Cochrane risk-of-bias tool was used to assess the quality of studies. Meta-analyses were performed using a bivariate random-effects model. Statistical analyses were performed using R Software 4.2.3 and heterogeneity was assessed with I 2 statistics. Results: Seven trials were included with 796 patients (61% female). Amitriptyline was associated with better treatment response (OR, 5.30; 95% CI, 2.47 to 11.39; P < 0.001), reduced Irritable Bowel Syndrome Symptom Severity Scores (MD, –50.72; 95% CI, –94.23 to –7.20; P = 0.020) and improved diarrhea (OR, 10.55; 95% CI, 2.90 to 38.41; P < 0.001). No significant difference between the 2 groups regarding the adverse effects was observed. Three trials showed an overall low risk of bias, 2 trials showed an overall high risk of bias due to randomization and missing data, and 2 trials had some concerns regarding missing data. Conclusions Amitriptyline was found to be well-tolerated and effective in treating IBS compared to placebo. These findings support the use of amitriptyline for the management of IBS, particularly among patients with the IBS diarrhea subtype. Future research should focus on the dose-dependent effects of amitriptyline in IBS to better guide clinicians in personalized titration regimens.

The pharmaceutical research sector is highly interested in oral gastro-retentive dose formulations. The significance of gastro-retentive drug delivery systems (GRDDS) has grown as these systems enhance patient compliance and improve the therapeutic indices of medications. Various technical advancements in the design and production of gastro-retentive dosage forms can overcome physiological limitations, such as short gastric retention time and fluctuations in stomach emptying. Medications with shorter half-lives, instability or poor solubility at alkaline pH, or inadequate absorption in the lower gastrointestinal tract can greatly benefit from GRDDS. To achieve the desired retention period and release pattern, these systems can be developed using a range of innovative methods, including magnetic, bioadhesive, expandable, and floating systems. The use of GRDDS for oral drug administration has significantly increased in recent years, with innovative design strategies—such as the widely used floating drug delivery system—playing a major role. GRDDS offer several advantages, including the ability to provide drugs with a narrow absorption window, improved pharmacological effects, reduced dosing frequency, enhanced bioavailability, and prolonged drug residence in the stomach for local effects such as the treatment of peptic ulcer disease. This study provides a brief introduction to gastro-retentive drug delivery, covering its necessity, advantages, disadvantages, influencing factors, approaches, and applications.

Purpose: This study aimed to determine the effect of tumor resection on dysbiosis of the intestinal microbiota in patients with right-sided colon cancer. Methods: This study utilized a longitudinal design to explore the outcomes of patients diagnosed with right-sided colon cancer who underwent surgical resection at Dr. M. Djamil General Hospital from July to December 2023. We excluded patients with a documented history of comorbidities, specifically those affecting the digestive system. To compare the microbiota (genus and phylum) between patients with right-sided colon cancer and the control group, we conducted bivariate analyses using the independent t-test or Mann-Whitney test. Furthermore, we employed the dependent t-test or Wilcoxon test to assess changes in the dysbiosis of the microbiota (genus and phylum) before and after resection. A P-value of <0.05 was considered statistically significant. Results: This study included a total of 21 patients diagnosed with right-sided colon cancer. In the control group, Bacteroidetes constituted the highest proportion of intestinal microbiota, accounting for 56.34%. Prior to tumor resection, the intestinal microbiota of patients exhibited Proteobacteria as the predominant phylum, representing 52.97%. Following tumor resection, Bacteroidetes remained the most prevalent, comprising 50.9% of the intestinal microbiota. Significant variations in the levels of Proteobacteria, Verrucomicrobia, and Cyanobacteria/Chloroplast were observed in the intestinal microbiota of patients with right-sided colorectal cancer before and after tumor excision (all P=0.001). Conclusion The microbiome of patients with right-sided colorectal cancer differed significantly from that of the control group. However, following tumor resection, the microbiome composition of these patients became more similar to that observed in the control group.