-
Drug Design, Development and Therapy 2023Baiyu Decoction (BYD), a clinical prescription of traditional Chinese medicine, has been proven to be valuable for treating ulcerative colitis (UC) by enema. However,...
Integrated Network Pharmacology, Molecular Docking and Animal Experiment to Explore the Efficacy and Potential Mechanism of Baiyu Decoction Against Ulcerative Colitis by Enema.
BACKGROUND
Baiyu Decoction (BYD), a clinical prescription of traditional Chinese medicine, has been proven to be valuable for treating ulcerative colitis (UC) by enema. However, the mechanism of BYD against UC remains unclear.
PURPOSE
A combination of bioinformatics methods including network pharmacology and molecular docking and animal experiments were utilized to investigate the potential mechanism of BYD in the treatment of UC.
MATERIALS AND METHODS
Firstly, the representative compounds of each herb in BYD were detected by liquid chromatography-mass spectrometry. Subsequently, we predicted the core targets and potential pathways of BYD for treating UC through network pharmacology. And rat colitis model was established with dextran sodium sulfate. UC rats were subjected to BYD enema administration, during which we recorded body weight changes, disease activity index, and colon length to assess the effectiveness of BYD. Besides, quantitative real-time PCR, western blotting, ELISA and immunofluorescence were used to detect intestinal inflammatory factors, intestinal barrier biomarkers and TOLL-like receptor pathway in rats. Finally, the core components and targets of BYD were subjected to molecular docking so as to further validate the results of network pharmacology.
RESULTS
A total of 41 active compositions and 203 targets related to BYD-UC were subjected to screening. The results of bioinformatics analysis showed that quercetin and kaempferol may be the main compounds. Additionally, AKT1, IL-6, TP53, TNF and IL-1β were regarded as potential therapeutic targets. KEGG results explained that TOLL-like receptor pathway might play a pivotal role in BYD protecting against UC. In addition, animal experiments and molecular docking validated the network pharmacology results. BYD enema treatment can reduce body weight loss, lower disease activity index score, reverse colon shortening, relieve intestinal inflammation, protect intestinal barrier, and inhibit TOLL-like receptor pathway in UC rats. Besides, molecular docking suggested that quercetin and kaempferol docked well with TLR4, AKT1, IL-6, TP53.
CONCLUSION
Utilizing network pharmacology, animal studies, and molecular docking, enema therapy with BYD was confirmed to have anti-UC efficacy by alleviating intestinal inflammation, protecting the intestinal barrier, and inhibiting the TOLL-like receptor pathway. Researchers should focus not only on oral medications but also on the rectal administration of medications in furtherance of the cure of ulcerative colitis.
Topics: Animals; Rats; Colitis, Ulcerative; Kaempferols; Molecular Docking Simulation; Animal Experimentation; Interleukin-6; Network Pharmacology; Quercetin; Enema; Toll-Like Receptors; Inflammation; Dextran Sulfate; Drugs, Chinese Herbal; Disease Models, Animal
PubMed: 38024534
DOI: 10.2147/DDDT.S432268 -
Cancer Treatment and Research... 2024One of the cancers that affect men, prostate cancer considerably raises mortality rates for males around the world. Patients with prostate cancer can have a localized or... (Review)
Review
One of the cancers that affect men, prostate cancer considerably raises mortality rates for males around the world. Patients with prostate cancer can have a localized or advanced form of the illness. Digital rectal examinations, prostate-specific antigen analyses, and prostate biopsies are all used to identify prostate cancer. The onset, development, and spread of cancer are all correlated with mutations in specific genes. Radical prostatectomy, ablative radiation, and active surveillance are all forms of treatment for localized prostate cancer. Androgen deprivation therapy (ADT), radiation, and chemotherapy are given to men who have metastatic prostate cancer or have experienced a relapse. When compared to traditional cancer chemotherapeutic methods, the liposome-based drug delivery technology offers less toxic, biodegradable, and biocompatible nanomedicine. Liposomes offer great advantages for use in nanomedicines by improving the sensitivity, specificity, and persistence of these anti-malignant cell agents in the body. Liposomal formulations are undergoing clinical trials of variety of cancers including prostate cancer. The present narrative review describes the composition and types of liposomes, its advantages, disadvantages, and the methods of preparation, research studies, clinical applications, drug repurposing and administration.
Topics: Humans; Liposomes; Male; Prostatic Neoplasms; Antineoplastic Agents; Drug Delivery Systems; Nanomedicine
PubMed: 38367412
DOI: 10.1016/j.ctarc.2024.100792 -
Animals : An Open Access Journal From... Nov 2023Intrapartum asphyxia, fetal hypoxia, and their consequences (e.g., acidosis, hypercapnia, hypoglycemia, and hypothermia) are the main factors related to physio-metabolic...
Caffeine Administration in Piglets with Low Birthweight and Low Vitality Scores, and Its Effect on Physiological Blood Profile, Acid-Base Balance, Gas Exchange, and Infrared Thermal Response.
Intrapartum asphyxia, fetal hypoxia, and their consequences (e.g., acidosis, hypercapnia, hypoglycemia, and hypothermia) are the main factors related to physio-metabolic imbalances that increase neonatal mortality in piglets, particularly in piglets with low birthweight and low vitality scores. This study aimed to evaluate the effect of three different doses of caffeine (10, 20, and 30 mg/kg) administered orally to 480 newborn piglets with low birthweight and low vitality scores. Blood gas parameters (pH, pO, pCO, and HCO), physio-metabolic profile (Ca, glucose, and lactate), and the thermal response assessed through infrared thermography in four thermal windows (ocular, auricular, snout, and hindlimb) and rectal temperature were evaluated during the first 24 h of life. Doses of 30 mg/kg resulted in significant differences at 24 h for all evaluated parameters, suggesting that caffeine administration improved the cardiorespiratory function and metabolic activity of piglets by reducing acidosis, restoring glycemia, and increasing surface and rectal temperature. In conclusion, caffeine at 30 mg/kg could be suggested as an appropriate dose to use in piglets with low birthweight and low vitality scores. Future research might need to study the presentation of adverse effects due to higher caffeine concentrations.
PubMed: 38003109
DOI: 10.3390/ani13223491 -
BMC Microbiology Sep 2023It has become clear that the intestinal microbiota plays a role in food allergies. The objective of this study was to assess the food allergy-preventive effects of...
BACKGROUND
It has become clear that the intestinal microbiota plays a role in food allergies. The objective of this study was to assess the food allergy-preventive effects of combined intake of a short fructan (1-kestose [Kes]) and a long fructan (inulin ([Inu]) in an ovalbumin (OVA)-induced food allergy mouse model.
RESULTS
Oral administration of fructans lowered the allergenic symptom score and alleviated the decreases in rectal temperature and total IgA levels and increases in OVA-specific IgE and IgA levels induced by high-dose OVA challenge, and in particular, combined intake of Kes and Inu significantly suppressed the changes in all these parameters. The expression of the pro-inflammatory cytokine IL-4, which was increased in the allergy model group, was significantly suppressed by fructan administration, and the expression of the anti-inflammatory cytokine IL-10 was significantly increased upon Kes administration. 16 S rRNA amplicon sequencing of the gut microbiota and beta diversity analysis revealed that fructan administration may induce gut microbiota resistance to food allergy sensitization, rather than returning the gut microbiota to a non-sensitized state. The relative abundances of the genera Parabacteroides B 862,066 and Alloprevotella, which were significantly reduced by food allergy sensitization, were restored by fructan administration. In Parabacteroides, the relative abundances of Parabacteroides distasonis, Parabacteroides goldsteinii, and their fructan-degrading glycoside hydrolase family 32 gene copy numbers were increased upon Kes or Inu administration. The concentrations of short-chain fatty acids (acetate and propionate) and lactate were increased by fructan administration, especially significantly in the Kes + Inu, Kes, and Inu-fed (Inu, Kes + Inu) groups.
CONCLUSION
Combined intake of Kes and Inu suppressed allergy scores more effectively than single intake, suggesting that Kes and Inu have different allergy-preventive mechanisms. This indicates that the combined intake of these short and long fructans may have an allergy-preventive benefit.
Topics: Animals; Mice; Gastrointestinal Microbiome; Fructans; Food Hypersensitivity; Cytokines; Immunoglobulin A
PubMed: 37737162
DOI: 10.1186/s12866-023-03021-6 -
Patient Preference and Adherence 2024In the US, 3 rescue treatment options are approved for patients with seizure clusters (ie, acute repetitive seizures), which are intermittent increases of seizure... (Review)
Review
In the US, 3 rescue treatment options are approved for patients with seizure clusters (ie, acute repetitive seizures), which are intermittent increases of seizure activity. This narrative PubMed review of these 3 treatments examines newer intranasal options that are well suited for adolescent and adult patients who may desire a transition from rectal treatment. Diazepam rectal gel is indicated for patients ≥2 years, diazepam nasal spray for those ≥6 years, and midazolam nasal spray for those ≥12 years. Approvals for diazepam rectal gel and midazolam nasal spray were based on safety and efficacy comparisons with placebo. Approval for diazepam nasal spray was based on results from long-term safety and tolerability studies in addition to its comparable bioavailability to diazepam rectal gel, while also showing less interpatient variability. The safety profiles of diazepam rectal gel and nasal spray are similar, and the medications share safety, warning, and precaution labeling. Thus, patients ≥6 years could be introduced to intranasal diazepam, allowing for continuity of familiar treatment while improving access and comfort. Intranasal midazolam also has a well-characterized safety profile. A proxy for effectiveness is the number of seizure clusters that were treated with a single dose, and these differed in separate, noncomparative studies. The safety and effectiveness of diazepam nasal spray have been examined in multiple subpopulations, whereas patient/caregiver experiences with both approved intranasal formulations have been characterized. Users may prefer nasal administration because it is noninvasive and effective, and provides social advantages, comfort, ease of use, and less variability compared with rectal gel. Nasal sprays are portable and convenient for use in the community (school, work, travel), and self-administration was reported in one study, with patients as young as 11 years old self-administering diazepam nasal spray. These newer, intranasal rescue treatments for seizure clusters provide an alternative to the rectal route.
PubMed: 38344151
DOI: 10.2147/PPA.S447028 -
Cureus Feb 2024Background In pediatric dentistry, sedation aims to eliminate anxiety to facilitate the completion of dental procedures. Sedation in children is a multidimensional field...
Background In pediatric dentistry, sedation aims to eliminate anxiety to facilitate the completion of dental procedures. Sedation in children is a multidimensional field that includes the child, parents/guardians, and the health care team. The rectal route is generally painless, making it suitable for children who are afraid of needles. This route has several advantages over the oral route, including reduced patient cooperation requirements, a faster and more predictable onset, and less physical trauma than the intravenous and intramuscular routes. This case series aimed to evaluate the effectiveness and success rate of rectal sedation with ketamine and midazolam in the management of uncooperative children during dental treatment. Case presentation Ten healthy children with definitely negative behavior were enrolled in this study. Each child was given 7 mg/kg of ketamine in combination with midazolam 0.1 mg/kg by the rectal route. The mean onset sedation time was 9.5 minutes, and pulpotomy procedures were done. Behavioral response was monitored throughout treatment using the Ohio State University Behavioral Rating Scale (OSUBRS), and the depth of sedation was measured using the University of Michigan Sedation Scale (UMSS). The Houpt General Behavior Scale was used to estimate the treatment success rate based on the overall behavior rating. All 10 cases showed good anxiolysis and cooperation following rectal administration, with no side effects observed. Conclusions Rectal administration of ketamine in combination with midazolam may be considered a reliable method in the management of uncooperative children during dental treatment. No adverse effects were observed during or after the sedation procedure.
PubMed: 38529445
DOI: 10.7759/cureus.54825 -
Medicina (Kaunas, Lithuania) Dec 2023: Approximately 5-10% of all patients with metastatic colorectal cancer (mCRC) harbor a mutation. These patients exhibit distinct metastatic patterns, poor prognosis,... (Observational Study)
Observational Study
Real-World Outcomes of First-Line FOLFIRI Plus Bevacizumab with Irinotecan Dose Escalation versus FOLFOXIRI Plus Bevacizumab in -Mutant Metastatic Colorectal Cancer: The Preliminary Data from a Single-Center Observational Study.
: Approximately 5-10% of all patients with metastatic colorectal cancer (mCRC) harbor a mutation. These patients exhibit distinct metastatic patterns, poor prognosis, and heterogenous survival outcomes. The findings from the TRIBE study indicated that the administration of FOLFOXIRI plus bevacizumab as first-line treatment extended the median duration of overall survival (OS). In this study, we explored the effects of polymorphism on the outcomes of irinotecan dose escalation versus FOLFOXIRI plus bevacizumab in patients with -mutant mCRC. : We retrospectively reviewed the medical records of 25 patients who had received a diagnosis of -mutant mCRC between October 2015 and August 2022. All patients underwent genotyping before receiving bevacizumab plus FOLFIRI. The primary end point was progression-free survival (PFS), and secondary endpoints were OS and adverse events (AEs). The two treatment arms were compared in terms of 6-month PFS and 12-month OS. : Over a median follow-up duration of 15.0 (interquartile range, 10.0-30.5) months, no significant differences were noted between the treatment arms in severe AEs (SAEs), 6-month PFS, or 12-month OS (all < 0.05). Regarding AEs, the FOLFIRI plus bevacizumab regimen was associated with a lower incidence of anorexia than was the FOLFOXIRI plus bevacizumab regimen ( = 0.042). : Our findings indicate that FOLFIRI plus bevacizumab with irinotecan dose escalation is an effective first-line treatment regimen for patients with -mutant mCRC. This regimen leads to acceptable clinical outcomes with manageable AEs. However, the effects on survival and safety outcomes could only be speculated, and further studies are needed because of the sample size, the follow-up for the OS evaluation, and the non-uniformity in all the variables considered in the two groups.
Topics: Humans; Bevacizumab; Irinotecan; Proto-Oncogene Proteins B-raf; Colorectal Neoplasms; Retrospective Studies; Preliminary Data; Camptothecin; Fluorouracil; Colonic Neoplasms; Rectal Neoplasms; Antineoplastic Combined Chemotherapy Protocols
PubMed: 38138211
DOI: 10.3390/medicina59122108 -
BioRxiv : the Preprint Server For... Aug 2023Despite extensive human use of the inhalation route for ingesting opioids, models in rodents have mostly been limited to parenteral injection and oral dosing. Methods...
RATIONALE
Despite extensive human use of the inhalation route for ingesting opioids, models in rodents have mostly been limited to parenteral injection and oral dosing. Methods using electronic drug delivery systems (EDDS; "e-cigarettes") have shown efficacy in rodent models but these do not faithfully mimic the most popular human inhalation method of heating heroin to the point of vaporization.
OBJECTIVE
This study was designed to determine if direct volatilization of heroin hydrochloride delivers effective heroin doses to rodents.
METHODS
Middle aged rats were exposed to vapor created by direct heating of heroin HCl powder in a ceramic e-cigarette type atomizer. Efficacy was determined with a warm water tail withdrawal nociception assay, rectal temperature and self-administration.
RESULTS
Ten minutes of inhalation of vaporized heroin slowed response latency in a warm water tail withdrawal assay and increased rectal temperature in male rats, in a dose-dependent manner. Similar antinociceptive effects in female rats were attenuated by the opioid antagonist naloxone (1.0 mg/kg, s.c.). Female rats made operant responses for heroin vapor in 15-minute sessions, increased their response rate when the reinforcement ratio increased from FR1 to FR5, and further increased their responding when vapor delivery was omitted. Anti-nociceptive effects of self-administered volatilized heroin were of a similar magnitude as those produced by the 10-minute non-contingent exposure.
CONCLUSIONS
This study shows that "chasing the dragon" methods of inhalation of heroin can be modeled successfully in the rat. Inhalation techniques may be particularly useful for longer term studies deep into middle age of rat species.
PubMed: 37786688
DOI: 10.1101/2023.08.09.552712 -
International Journal of Colorectal... May 2024A high number of topical products are available for the treatment of hemorrhoidal symptoms. Sucralfate-based topical products constitute a new treatment alternative that... (Observational Study)
Observational Study
BACKGROUND AND AIMS
A high number of topical products are available for the treatment of hemorrhoidal symptoms. Sucralfate-based topical products constitute a new treatment alternative that act as a mechanical barrier to facilitate healing. The aim of this prospective, observational study was to determine patient- and physician-assessed effectiveness and tolerability of rectal ointment and suppositories containing sucralfate for the treatment of hemorrhoidal symptoms in routine clinical practice.
METHODS
Adult patients with diagnosed, mild-to-moderate, symptomatic non-bleeding hemorrhoids treated with rectal ointment or suppositories containing sucralfate were enrolled. Patients were administered treatment twice per day for at least 1 week until symptom resolution and/or for a maximum of 4 weeks. The primary endpoint was patient-assessed effectiveness on a modified Symptom Severity Score (mSSS, range 0 to 14). Physician-assessed effectiveness (9 symptoms, 0 to 5 Likert scale), hemorrhoid grade, and patient satisfaction were also determined.
RESULTS
Five investigators enrolled 60 patients; mean age was 48.4 ± 16.6 years and 72.4% were female. Pain or pressure sensitivity was reported as the most severe symptom by patients, and pressure sensitivity, discharge, soiling, and prolapse by physicians. Mean patient-assessed mSSS at baseline was 6.6 ± 1.9 and was significantly improved overall and in the ointment and suppository groups individually by -4.6 ± 2.0, -4.4 ± 1.8, and -4.8 ± 2.2, respectively (p < 0.0001). Investigator-assessed mean baseline symptom score was 18.1 ± 3.9 and improved by -7.1 ± 4.5, -6.9 ± 5.4, and -7.3 ± 3.5, respectively (p < 0.0001). Investigator-assessed symptoms of pressure sensitivity, swelling, and discharge were improved to the greatest extent. Hemorrhoid grade was improved in 38% of patients at the end of treatment. Compliance with treatment was 97.4% and patient satisfaction with application and onset of action was high (81.3% and 76.2%, respectively). Both the ointment and suppository were well tolerated.
CONCLUSIONS
The effectiveness of topical ointment or suppository containing sucralfate on patient- and investigator-assessed hemorrhoidal symptoms in real-life clinical practice was demonstrated. Patient satisfaction was high and treatments were well tolerated. Larger controlled trials are warranted to confirm the results.
Topics: Humans; Sucralfate; Hemorrhoids; Female; Suppositories; Male; Middle Aged; Ointments; Prospective Studies; Treatment Outcome; Patient Satisfaction; Adult; Aged; Administration, Rectal
PubMed: 38750150
DOI: 10.1007/s00384-024-04642-7