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1.
Article | IMSEAR | ID: sea-234399

ABSTRACT

Cardiovascular diseases (CVDs) pose a significant global health challenge, with India bearing a disproportionate burden of CVD-related morbidity and mortality. Hypertension (HTN) is a major risk factor for CVDs, affecting nearly 30% of the Indian population. Achieving target blood pressure (BP) levels is crucial for reducing cardiovascular risk, necessitating aggressive antihypertensive therapy. Combination therapy has emerged as a cornerstone in HTN management, especially in high-risk patients. This review delves into the literature and perspectives of Indian cardiologists on combination therapy for HTN management. Despite the efficacy of contemporary antihypertensive medications, a substantial proportion of patients fail to reach target BP levels with monotherapy. Combination therapy offers synergistic effects, addressing multiple pathways involved in HTN pathogenesis. Recent guidelines recommend initiating treatment with two-drug combinations, transitioning to three-drug combinations in resistant cases. Combination therapy not only enhances BP control but also reduces the risk of cardiovascular events and mortality compared to monotherapy. Optimal management of HTN requires personalized approaches, considering individual patient profiles and comorbidities such as coronary artery disease (CAD), diabetes mellitus (DM), dyslipidemia, and heart failure (HF). In such cases, combination therapy plays a pivotal role in mitigating cardiovascular risks. ARB/CCB combination therapy, particularly telmisartan/amlodipine, demonstrates significant efficacy and tolerability across various patient populations, including those with metabolic risk factors and renal impairment. Expert recommendations highlight the importance of individualized therapy, patient education, early diagnosis, and initiation with dual therapy in India. Strategies to improve medication adherence and compliance, such as single-pill double or triple combinations, are emphasized. Moreover, awareness of newer treatment options and contactless diagnostic instruments is crucial for optimizing HTN management. In conclusion, combination therapy stands as a cornerstone in HTN management, offering enhanced efficacy, tolerability, and cardiovascular protection. Tailored approaches guided by expert recommendations are essential to address the growing burden of HTN and reduce the socioeconomic impact of CVDs in India.

2.
Article | IMSEAR | ID: sea-231647

ABSTRACT

The purpose of the trial was to determine whether combination medication for type 2 diabetes mellitus offers better glycemic control than monotherapy. Subjects whose ages were more than 18 years and with glycated hemoglobin levels higher than 7.5% were enrolled. Among the 664 patients enrolled, 332 received monotherapy, while 332 were treated with combination therapy. The treatment groups received either vildagliptin + metformin combination therapy or metformin monotherapy. Vildagliptin, as an adjunct to metformin treatment, was to be evaluated for its safety and efficacy in reducing HbA1c levels from baseline. The study included individuals with a history of T2DM for 3 to 4 years who had been treated with either combination therapy or monotherapy for at least three months. Statistical analysis was done using SPSS software. As per the findings, it indicated that combination therapy led to a considerably greater reduction in glycated hemoglobin levels compared to monotherapy. Adverse events were also observed to vary significantly between the two treatment cohorts. Outcomes suggest that combination medication should be started earlier than monotherapy for superior glycemic control. Additionally, it was thought that the combo therapy had a positive safety profile.

3.
Article in Chinese | WPRIM | ID: wpr-1030019

ABSTRACT

Objective:To investigate the clinical efficacy of a 1 064 nm picosecond laser combined with intense pulsed light in the treatment of melasma.Methods:From May to August 2022, ninety-two female patients with melasma were admitted to the Medical Cosmetology Center, Xi′an International Medical Center Hospital, aged 25-50 years, with an average age of (35.0±3.5) years. The were divided by random number table method. Forty-six cases were divided into laser combined group, which were treated with precise intense pulsed light combined with a 1 064 nm picosecond laser. Forty-six cases in the laser group were treated with a 1 064 nm picosecond laser. The area and severity score of melasma (MASI), VISIA score and clinical efficacy were evaluated.Results:The MASI scores of laser combined group were 12.58 (11.04, 13.99) before treatment, and the MASI scores of laser group were 13.16 (11.47, 14.14) before treatment. The MASI scores of laser combined group were 5.75 (3.79, 7.19), and the MASI scores of laser group were 7.15 (5.42, 5.85) after treatment. The MASI scores of the two groups were decreased compared with those before treatment, and the MASI score of the laser combined group was lower than that of the laser group. The difference was statistically significant ( Z=-4.05, P<0.01). The median VISIA scores of the laser combined group were (173.72±43.77), and the median VISIA scores of the laser group were (175.65±34.9) before treatment. The median VISIA scores of the laser combined group were (135.46±41.63), and the median VISIA scores ofthe laser group were (145.26±33.33) after treatment. The VISIA scores of the two groups were decreased compared with those before treatment. The scores of the laser combined group were lower than those of the laser group. The difference was statistically significant ( t=-2.52, P<0.05). The effective rate of the laser combined group (80.43%, 37/46) was higher than that of the laser group (69.56%, 22/46, P<0.05). Conclusions:The curative effect of 1 064 nm picosecond laser combined with precise intense pulsed light in the treatment of melasma is better than that of a 1 064 nm picosecond laser alone.

4.
Article in Chinese | WPRIM | ID: wpr-1003791

ABSTRACT

A sesquiterpene natural substance called artemisinin was discovered in Artemisia annua. One of its derivatives, artesunate (ART), has the properties of economy, immediate effect, low toxicity, and good tolerance. Since it has a quick and powerful killing effect on plasmodium in the erythrocyte phase and can quickly handle clinical seizure and symptoms, it is currently mostly utilized to treat cerebral malaria and other severe instances of malaria. In addition, it has antitumor, antivirus, anti-hepatic fibrosis, anti-inflammatory, antibacterial, hepatocyte protection, immunological modulation, and other pharmacological properties and can inhibit cell proliferation, induce cell apoptosis, and reduce the incidence of sepsis. In many countries, artemisinin-based combination therapies (ACTs), such as artemether-benflumetol, artesunate-amodiaquine, and artemether-lumefantrine, are the first-line treatments for malaria. Recent research on artesunate by Chinese and international scholars has revealed that compared with monotherapy, artesunate combination therapy offers more benefits in terms of improving pharmacological effects, shortening the duration of medicine, and minimizing adverse effects. Through systematic retrieval of Web of Science Core Collection and integration through CiteSpace (6.2.1) software, this article reviewed the mechanism of artesunate combined with other medications with regard to antimalarial, antitumor, antibacterial, and antiviral features in the previous five years, so as to provide some theoretical basis for rational development and utilization of ART and new drug research and development.

5.
Acta Pharmaceutica Sinica B ; (6): 335-349, 2024.
Article in English | WPRIM | ID: wpr-1011248

ABSTRACT

Targeting multiple immune mechanisms may overcome therapy resistance and further improve cancer immunotherapy for humans. Here, we describe the application of virus-like vesicles (VLV) for delivery of three immunomodulators alone and in combination, as a promising approach for cancer immunotherapy. VLV vectors were designed to deliver single chain interleukin (IL)-12, short-hairpin RNA (shRNA) targeting programmed death ligand 1 (PD-L1), and a dominant-negative form of IL-17 receptor A (dn-IL17RA) as a single payload or as a combination payload. Intralesional delivery of the VLV vector expressing IL-12 alone, as well as the trivalent vector (designated CARG-2020) eradicated large established tumors. However, only CARG-2020 prevented tumor recurrence and provided long-term survival benefit to the tumor-bearing mice, indicating a benefit of the combined immunomodulation. The abscopal effects of CARG-2020 on the non-injected contralateral tumors, as well as protection from the tumor cell re-challenge, suggest immune-mediated mechanism of protection and establishment of immunological memory. Mechanistically, CARG-2020 potently activates Th1 immune mechanisms and inhibits expression of genes related to T cell exhaustion and cancer-promoting inflammation. The ability of CARG-2020 to prevent tumor recurrence and to provide survival benefit makes it a promising candidate for its development for human cancer immunotherapy.

6.
Article in Chinese | WPRIM | ID: wpr-1017743

ABSTRACT

Spinal muscular atrophy(SMA),an autosomal recessive genetic disease characterized by progressive weakness and atrophy of the proximal limbs caused by degeneration of motor neurons in the anterior horn of the spinal cord,can affect multiple systems such as respiratory,digestive,and skeletal systems. Untreated children with severe type 1 SMA usually die within 2 years of age. In recent years,the treatment of SMA has developed rapidly,and a variety of drugs have been approved to benefit patients. However,none of the existing therapeutic drugs or regimens can achieve a complete cure. Therefore,the combination of different therapeutic drugs and the research and development of new drugs may be the way forward for the treatment of SMA. The latest progress of therapeutic drugs and combination therapy in SMA are summarized in this review,which may be helpful for guiding the treatment of SMA.

7.
Journal of Clinical Surgery ; (12): 92-95, 2024.
Article in Chinese | WPRIM | ID: wpr-1019301

ABSTRACT

In recent years,there have been significant advancements in tumor immunotherapy.Immune checkpoint inhibitors have emerged as a pivotal approach for treating advanced malignant tumors.The use of immunotherapy has been widely recommended and applied in clinical treatment both domestically and internationally.However,its clinical treatment efficacy still falls short of expectations.Improving the efficacy of immunotherapy for patients with advanced malignant tumors is currently a prominent research focus.Studies indicate that the combined use of immune enhancers and immune checkpoint inhibitors in various advanced malignant tumors significantly enhances the outcomes of immunotherapy.This article primarily highlights the combined application of immune enhancers and immune checkpoint inhibitors in cancer therapy,offering insights into their potential in the field of oncology treatment.

8.
Article in Chinese | WPRIM | ID: wpr-1021241

ABSTRACT

BACKGROUND:In recent years,a variety of lasers have been widely used in various diseases related to stomatology,including the prevention and treatment of dental caries. OBJECTIVE:To investigate the effect of neodymium-doped:yttrium aluminum perovskite(Nd:YAP)laser combined with two remineralizers on early enamel caries in vitro. METHODS:Early enamel caries models in vitro were artificially established by 60 enamel blocks and randomly divided into 6 groups(n=10).Group A did not undergo any treatment but underwent extracorporeal pH circulation.Group B underwent remineralization of dentin(the main component of casein phosphopeptide-amorphous calcium phosphate composite)and extracorporeal pH circulation.Group C underwent remineralization treatment of Sensodyne toothpaste(the main component of bioactive glass)and then underwent extracorporeal pH circulation.Group D received Nd:YAP laser irradiation and extracorporeal pH circulation.Group E was treated with Nd:YAP laser irradiation,with remineralization of dentin,and then with extracorporeal pH circulation.In group F,Nd:YAP laser irradiation was performed,and then Sensodyne toothpaste was used for remineralization,and the extracorporeal pH circulation was performed;the remineralization treatment was conducted twice a day,and the experimental period was 20 days.Group G was a normal control group,without caries or remineralization,but only underwent extracorporeal pH circulation.After the experiment,the microhardness,morphology and Ca/P ratio of the dental enamel surface were measured in each group. RESULTS AND CONCLUSION:(1)The surface microhardness value of dental enamel in groups B,C and D was higher than that in group A(P<0.000 1);the surface microhardness value of dental enamel in groups E and F was significantly higher than that in groups B,C and D(P<0.000 1),and the surface microhardness value of dental enamel in group F was significantly higher than that in group E(P<0.000 1).(2)Scanning electron microscopy showed that there were a lot of demineralized pores on the enamel surface of group A.There were mineral deposits on the enamel surface of group B,which were uneven and loose.In group C,there were a lot of mineral deposits on the enamel surface,and demineralized pores were found between the calcified masses.The enamel surface of group D was relatively flat;the demineralized pores were significantly smaller than that of group A,and the enamel column interstitium was damaged.In group E,the mineral deposits on the enamel surface were thicker and the demineralized pores were significantly reduced.The mineralized substances deposited on the enamel surface of group F were most dense and uniform and the demineralized pores were small.(3)The Ca/P ratio on the enamel surface of groups B and C was significantly higher than that of group A(P<0.000 1);the Ca/P ratio on the enamel surface of group E was significantly higher than that of groups B,C and D(P<0.000 1),and the Ca/P ratio on the enamel surface of group F was higher than that of group E(P<0.001).(4)These findings indicate that bioactive glass,casein phosphopeptide-amorphous calcium phosphate composite,and Nd:YAP laser after enamel demineralization can promote the remineralization of early enamel caries.Nd:YAP laser combined with bioactive glass or casein phosphopeptide-amorphous calcium phosphate composite can further strengthen the remineralization of dental enamel caries,and the combination of Nd:YAP laser and bioactive glass has the best effect.

9.
Article in Chinese | WPRIM | ID: wpr-1021661

ABSTRACT

BACKGROUND:Spinal cord injury not only causes serious physical and psychological injuries to patients but also brings a heavy economic burden to society.Spinal cord injury is initially triggered by mechanical trauma,followed by secondary injuries,and as the disease progresses,a glial scar develops. OBJECTIVE:To summarize the pathological process of spinal cord injury and strategies for stem cell transplantation to repair spinal cord injury,aiming to provide the best protocol for treating spinal cord injury. METHODS:Computer search was used to search PubMed and CNKI databases.Chinese search terms were"stem cell transplantation,spinal cord injury".English search terms were"stem cell,spinal cord injury,spinal cord,mesenchymal stem cells,neural stem cells,pathophysiology,clinical trial,primary injury,secondary injury".The literature was screened according to the inclusion and exclusion criteria.Finally,91 articles were included for review analysis. RESULTS AND CONCLUSION:(1)The strategies for repairing spinal cord injury through stem cell transplantation can be divided into exogenous stem cell transplantation and endogenous stem cell transplantation.The exogenous stem cell transplantation strategy for the treatment of spinal cord injury is divided into four kinds:injecting stem cells into the site of injury;transplantation of biomaterials loaded with stem cells;fetal tissue transplantation;transplantation of engineered neural network tissue or spinal cord-like tissue.(2)Compared with a single treatment method,combination therapy can more effectively promote nerve regeneration and spinal cord function recovery.(3)Microenvironment regulating the injury site,magnetic stimulation,electrical stimulation,epidural oscillating electric field stimulation,transcription factor overexpression and rehabilitation therapy can be combined with stem cell transplantation for combination therapy,thereby promoting the recovery of spinal cord function.

10.
Clinics ; Clinics;79: 100476, 2024. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1574737

ABSTRACT

Abstract Objective: This study investigated the effects of N-Acetylcysteine (NAC) combined with Ambroxol Hydrochloride (AH) on clinical symptoms, C-Reactive Protein (CRP), and Procalcitonin (PCT) levels in children with pneumonia. Methods: A total of 98 children with pneumonia were assigned to the control group and observation group by random number table method. NAC was administered to the observation group and AH was given to the control group. The therapeutic effect was observed, the disappearance time of clinical symptoms and levels of inflammatory factors, lung function parameters, blood gas analysis parameters, and immunoglobulin were measured. The incidence of adverse reactions was statistically analyzed. Results: A higher effective rate was observed in the observation group than in the control group (p < 0.05). Antipyretic time, cough disappearance time, and lung rale disappearance time in the observation group were shorter than those in the control group (p < 0.05). After treatment, CRP and PCT were lower (p < 0.05), FVC, FEV1, and FEV1/FVC were higher, PaCO2 was lower, PaO2 and SaO2 were higher, and IgA, IgG, IgM, and C3 were higher in the observation group than those in the control group (p < 0.05). The incidence of adverse reactions between the two groups was not significantly different (p > 0.05). Conclusion: NAC combined with AH is effective in the treatment of pediatric pneumonia by effectively alleviating clinical symptoms, reducing inflammatory factors, and improving lung function and immune function.

11.
Indian Pediatr ; 2023 Jun; 60(6): 447-452
Article | IMSEAR | ID: sea-225424

ABSTRACT

Objective: To compare the efficacy of desmopressin plus tolterodine (D+T) with desmopressin plus indomethacin (D+I) for treating enuresis in children. Design: Open-label randomized controlled trial. Setting: Bandar Abbas Children’s Hospital, a tertiary care children’s hospital in Iran, from March 21, 2018, to March 21, 2019. Participants: 40 children older than five years with monosymptomatic and non-monosymptomatic primary enuresis resistant to desmopressin monotherapy. Intervention: Patients were randomized to receive either D+T (60 µg sublingual desmopressin and 2 mg tolterodine) or D+I (60 µg sublingual desmopressin and 50 mg indomethacin) every night before bedtime for five months. Outcome: Reduction in the frequency of enuresis was evaluated at one, three, and five months, and response to treatment at five months. Drug reactions and complications were also noted. Results: After adjustment for age, consistent incontinence from toilet training, and non-monosymptomatic enuresis, D+T was significantly more efficacious than D+I; mean (SD) percent in nocturnal enuresis reduction at 1 [58.86 (7.27)% vs 31.18 (3.85) %; P<0.001], 3 [69.78 (5.99)% vs 38.56 (3.31)%; P<0.000], and 5 [84.84(6.21)% vs 39.14 (3.63)%; P<0.001] months showing a large effect. At 5 months, complete response to treatment was only observed with D+T, while treatment failure was significantly higher with D+I (50% vs 20%; P=0.047). None of the patients in either group developed cutaneous drug reactions or central nervous system symptoms. Conclusion: Desmopressin plus tolterodine appears to be superior to desmopressin plus indomethacin for treating pediatric enuresis resistant to desmopressin.

12.
Indian J Biochem Biophys ; 2023 Apr; 60(4): 331-338
Article | IMSEAR | ID: sea-221643

ABSTRACT

The aggregation of erythrocytes is an important mechanism for blood flow through the cardiovascular system. In malaria, this is complicated by infection caused by P. falciparum and is further complicated by the severity of parasitemia. Hence analysis of this micro-mechanism is essential to know the changes in blood not only in diseased conditions but also after artemisinin combination therapy (ASAQ) to alleviate suffering. For analysis purposes, aggregation of erythrocytes was determined by LED laser aggregometer, represented in terms of various parameters related to the changes in laser transmitted intensity. Formed aggregates are further analyzed by imaging and image-processing methods. For this study blood samples from young adults (18 – 40 years old) infected with P. falciparum (n= 80), without any other serious illness, were performed. These samples were selected based on the severity of parasitemia, and were divided into low (LP), medium1 (MP1), medium 2 (MP2), and high (HP) parasitemia. For three days, the selected individuals were treated with artemisinin-based combination therapy ASAQ (Artesunate 4 mg/kg and amodiaquine 10 mg base/ kg once a day). Healthy subjects (n=20) without any history of the disease were selected as a control group. The results, as obtained by various parameters, show a significant elevation of aggregation of erythrocytes (P< 0.05) in P. falciparum malaria with the increase of parasitemia level. There was a decrease in the aggregation after treatment on day four tending towards normal. Thus the current study shows the potential beneficial role of ASAQ on erythrocytes aggregation, which may contribute to reducing the harmful effects on various organs in P. falciparum-infected blood.

13.
Rev. cuba. med ; 62(1)mar. 2023.
Article in Spanish | LILACS, CUMED | ID: biblio-1450003

ABSTRACT

Introducción: El hipotiroidismo es una entidad de visita frecuente al endocrinólogo, establecer el mejor tratamiento es un desafío, a pesar del manejo adecuado y de un control hormonal óptimo, en ocasiones los pacientes continúan con los síntomas que afectan su calidad de vida, por lo que el tratamiento debe ser individualizado, basado en la mejor evidencia. Objetivo: Establecer las mejores opciones terapéuticas en las diferentes formas de presentación del hipotiroidismo. Métodos: Se realizó una búsqueda bibliográfica no sistemática en las bases de datos de PubMed, Medline, LILACS, EMBASE, Redalyc y guías internacionales. Los criterios de inclusión fueron publicaciones en inglés y español, en las que el título, palabras clave o resumen incluyen información pertinente al objetivo de estudio, periodicidad no mayor a los 5 años a excepción de las guías que son las últimas revisiones. En la búsqueda se obtuvieron 30 artículos de los cuales fueron 14 seleccionados. Conclusiones: Se establecieron las opciones terapéuticas con el fin de obtener un mejor tratamiento para el paciente hipotiroideo que debe ser individualizado y basado en la mejor evidencia, para alcanzar un control adecuado de su enfermedad, mejorar la calidad de vida y evitar complicaciones relacionadas con esta patología(AU)


Introduction: Hypothyroidism is an entity that is frequently seen at the endocrinologist´s. establishing the best treatment is a challenge, despite proper management and optimal hormonal control, sometimes patients continue with symptoms which affect their quality of life, therefore that treatment should be individualized, based on the best evidence. Objective: To establish the best therapeutic options in hypothyroidism different forms of presentation. Methods: A non-systematic bibliographic search was carried out in PubMed, Medline, LILACS, EMBASE, Redalyc databases and in the international guidelines. The inclusion criteria were publications in English and Spanish, in which the title, keywords or abstract include relevant information to the objective of the study, with a periodicity of no more than 5 years, except for the guidelines that the latest revisions were used. In the search, 30 articles were retrieved, 14 which were selected. Conclusions: The therapeutic options were established in order to find better treatment for hypothyroid patients, which must be individualized and based on the best evidence, to achieve adequate control of the disease, to improve the quality of life and to avoid related complications(AU)


Subject(s)
Humans , Male , Female , Thyroxine/therapeutic use , Combined Modality Therapy/methods , Hypothyroidism/drug therapy , Hypothyroidism/epidemiology
14.
Article | IMSEAR | ID: sea-232913

ABSTRACT

Background: Pulmonary arterial hypertension (PAH) is a severe condition marked by a progressive rise in pulmonary vascular resistance (PVR), which leads to right heart failure, and mortality. Combining medications is an appealing approach for treating PAH patients. The current study sought to compare the outcomes of monotherapy, and combination therapy after a short period of follow-up. The study aimed to compare the short-term outcome of monotherapy and combination therapy in the treatment of pulmonary hypertension. Methods: This randomized control trial study was conducted at the department of pediatric cardiology, Bangabandhu Sheikh Mujib medical university, national institute of cardiovascular disease, and national heart foundation, Dhaka, Bangladesh, from January 2018 to December 2018. During this period, a total of 70 participants were selected for the study following the inclusion, and exclusion criteria. The selected participants were then divided into two groups of 35 each through random selection. Result: There were no significant differences between the two groups in terms of mean age, and sex. The 34.3% in Group A, and 28.6% in group B had ventricular septal defects (VSD, followed by AVSD at 20.0% in group A and 25.7% in Group B. After 3 and 6 months of follow-up SpO2 per exercise, 6MWD, SpO2 post-exercise, and alanine aminotransferase showed statistically significant differences between single and combined groups. There was no statistically significant difference regarding adverse effects between the two groups. PASP was significantly decreased in the combined group than monotherapy group. Conclusions: Combination therapy is more successful than monotherapy in PAH with CHD. Combining bosentan with oral sildenafil medication in patients with CHD-related PAH is safe, and well tolerated at follow-ups.

15.
Article | IMSEAR | ID: sea-232900

ABSTRACT

Background: Pulmonary arterial hypertension (PAH) is a serious condition characterized by an increase in pulmonary vascular resistance (PVR) that leads to right heart failure and death. The study aimed to compare the side effects of monotherapy and combination therapy in the treatment of pulmonary hypertension Methods: This randomized control trial study was conducted at the department of pediatric cardiology, Bangabandhu Sheikh Mujib medical university, national institute of cardiovascular disease, and national heart foundation, Dhaka, Bangladesh. The study duration was 1 year, from January 2018 to December 2018. During this period, a total of 70 participants were selected for the study following the inclusion, and exclusion criteria from those diagnosed case of pulmonary hypertension with congenital heart disease admitted to the pediatric cardiology department, Bangabandhu Sheikh Mujib medical university, NICVD, NHF. Result: Maximum patients had ventricular septal defects (VSD) (34.3% in group A, and 28.6% in group B). Followed by AVSD. 20.0% in group A and 25.7% in group B. Atrial septal defect (ASD) were 14.3% in group A, and 17.1% in group B. After three, and 6 months of follow-up SpO2 per exercise, 6MWD, SpO2 post-exercise, and alanine aminotransferase showed statistically significant differences between single and combined groups. There was no statistically significant difference regarding adverse effects between the 2 groups, but group B patients had slightly higher incidence of some side effects. PASP was significantly decreased in combined group than monotherapy group. Conclusions: This study concludes that combination therapy is more successful than monotherapy in PAH with coronary heart disease (CHD). Our findings demonstrate that combining Bosentan with oral Sildenafil medication in patients with CHD-related PAH is safe, and well tolerated at 3-, and 6-month follow-ups, resulting in a significant improvement in clinical status, effort SpO2, exercise tolerance, hemodynamics, and PASP.

16.
Acta Pharmaceutica Sinica B ; (6): 542-558, 2023.
Article in English | WPRIM | ID: wpr-971723

ABSTRACT

Nonalcoholic fatty liver disease (NAFLD), especially nonalcoholic steatohepatitis (NASH), is a common hepatic manifestation of metabolic syndrome. However, there are no effective therapy to treat this devastating disease. Accumulating evidence suggests that the generation of elastin-derived peptides (EDPs) and the inhibition of adiponectin receptors (AdipoR)1/2 plays essential roles in hepatic lipid metabolism and liver fibrosis. We recently reported that the AdipoR1/2 dual agonist JT003 significantly degraded the extracellular matrix (ECM) and ameliorated liver fibrosis. However, the degradation of the ECM lead to the generation of EDPs, which could further alter liver homeostasis negatively. Thus, in this study, we successfully combined AdipoR1/2 agonist JT003 with V14, which acted as an inhibitor of EDPs-EBP interaction to overcome the defect of ECM degradation. We found that combination of JT003 and V14 possessed excellent synergistic benefits on ameliorating NASH and liver fibrosis than either alone since they compensate the shortage of each other. These effects are induced by the enhancement of the mitochondrial antioxidant capacity, mitophagy, and mitochondrial biogenesis via AMPK pathway. Furthermore, specific suppression of AMPK could block the effects of the combination of JT003 and V14 on reduced oxidative stress, increased mitophagy and mitochondrial biogenesis. These positive results suggested that this administration of combination of AdipoR1/2 dual agonist and inhibitor of EDPs-EBP interaction can be recommended alternatively for an effective and promising therapeutic strategy for the treatment of NAFLD and NASH related fibrosis.

17.
Acta Pharmaceutica Sinica B ; (6): 967-981, 2023.
Article in English | WPRIM | ID: wpr-971749

ABSTRACT

Platinum-based chemotherapy resistance is a key factor of poor prognosis and recurrence in hepatocellular carcinoma (HCC). Herein, RNAseq analysis revealed that elevated tubulin folding cofactor E (TBCE) expression is associated with platinum-based chemotherapy resistance. High expression of TBCE contributes to worse prognoses and earlier recurrence among liver cancer patients. Mechanistically, TBCE silencing significantly affects cytoskeleton rearrangement, which in turn increases cisplatin-induced cycle arrest and apoptosis. To develop these findings into potential therapeutic drugs, endosomal pH-responsive nanoparticles (NPs) were developed to simultaneously encapsulate TBCE siRNA and cisplatin (DDP) to reverse this phenomena. NPs (siTBCE + DDP) concurrently silenced TBCE expression, increased cell sensitivity to platinum treatment, and subsequently resulted in superior anti-tumor effects both in vitro and in vivo in orthotopic and patient-derived xenograft (PDX) models. Taken together, NP-mediated delivery and the co-treatment of siTBCE + DDP proved to be effective in reversing chemotherapy resistance of DDP in multiple tumor models.

18.
Article in Chinese | WPRIM | ID: wpr-965537

ABSTRACT

Alveolar echinococcosis, caused by Echinococcus multilocularis infection, is a highly deadly zoonotic parasitic disease. As a benzimidazole compound, albendazole has a strong and broad-spectrum anti-parasitic action. For alveolar echinococcosis patients that are unwilling to receive surgical treatment, lose the timing for surgery, or are intolerant to surgery due to poor physical status, administration of albendazole may delay disease progression. Recently, a large number of advances have been achieved in experimental studies on alveolar echinococcosis. In order to increase the understanding of the therapeutic efficacy of albendazole for alveolar echinococcosis, this review summarizes the advances in albendazole treatment for alveolar echinococcosis, so as to provide insights into the clinical treatment of alveolar echinococcosis with albendazole.

19.
Yao Xue Xue Bao ; (12): 274-284, 2023.
Article in Chinese | WPRIM | ID: wpr-965709

ABSTRACT

Photothermal therapy (PTT) has attracted significant attention due to minimal side effects and high treatment specificity. However, it often requires very high temperature to achieve complete tumor ablation under a single PTT. Such high temperature brings obvious thermal damage and inflammatory response to the body, affecting the therapeutic effect. In recent years, nitric oxide (NO) has been used to significantly inhibit tumor growth and enhance the sensitivity of tumor cells of temperature and drugs, thus enhancing the therapeutic effect. However, compounds as NO donors often have some disadvantages such as poor biocompatibility and untargeted delivery, etc., therefore, this medical application based on NO therapy is limited. In conclusion, the organic combination of NO donors and photothermal agents (PTAs) is expected to overcome the shortcomings of single therapy and achieve the antitumor effect of "1 + 1 > 2". In view of the rapid development of NO combining with PTT in tumor therapy, this review firstly introduces the antitumor mechanisms of different types of NO donors. Then the treatment strategy based on NO combined with PTT is discussed. Finally, the prospects and challenges of this combination therapy strategy in the clinical treatment of cancer are discussed.

20.
Zhonghua zhong liu za zhi ; (12): 259-264, 2023.
Article in Chinese | WPRIM | ID: wpr-969832

ABSTRACT

Objective: To investigate the clinical characteristics of abnormal liver function in patients with advanced esophageal squamous carcinoma treated with programmed death-1 (PD-1) antibody SHR-1210 alone or in combination with apatinib and chemotherapy. Methods: Clinical data of 73 patients with esophageal squamous carcinoma from 2 prospective clinical studies conducted at the Cancer Hospital Chinese Academy of Medical Sciences from May 11, 2016, to November 19, 2019, were analyzed, and logistic regression analysis was used for the analysis of influencing factors. Results: Of the 73 patients, 35 had abnormal liver function. 13 of the 43 patients treated with PD-1 antibody monotherapy (PD-1 monotherapy group) had abnormal liver function, and the median time to first abnormal liver function was 55 days. Of the 30 patients treated with PD-1 antibody in combination with apatinib and chemotherapy (PD-1 combination group), 22 had abnormal liver function, and the median time to first abnormal liver function was 41 days. Of the 35 patients with abnormal liver function, 2 had clinical symptoms, including malaise and loss of appetite, and 1 had jaundice. 28 of the 35 patients with abnormal liver function returned to normal and 7 improved to grade 1, and none of the patients had serious life-threatening or fatal liver function abnormalities. Combination therapy was a risk factor for patients to develop abnormal liver function (P=0.007). Conclusions: Most of the liver function abnormalities that occur during treatment with PD-1 antibody SHR-1210 alone or in combination with apatinib and chemotherapy are mild, and liver function can return to normal or improve with symptomatic treatment. For patients who receive PD-1 antibody in combination with targeted therapy and chemotherapy and have a history of long-term previous smoking, alcohol consumption and hepatitis B virus infection, liver function should be monitored and actively managed in a timely manner.


Subject(s)
Humans , Esophageal Squamous Cell Carcinoma/drug therapy , Esophageal Neoplasms/pathology , Prospective Studies , Programmed Cell Death 1 Receptor/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Liver Diseases/etiology
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