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PloS One 2023Considering the pharmacological treatment options for endometriosis-associated pain are confined to hormonal therapy and analgesics, we studied the analgesic effect of... (Randomized Controlled Trial)
Randomized Controlled Trial
Considering the pharmacological treatment options for endometriosis-associated pain are confined to hormonal therapy and analgesics, we studied the analgesic effect of 20 mg melatonin as an adjuvant therapy in women with endometriosis-associated pain. This randomized double-blinded, placebo-controlled trial was conducted at the Research Center for Womens' Health at Södersjukhuset, a university hospital in Stockholm, Sweden. Forty women from 18 to 50 years of age with endometriosis and severe dysmenorrhea with or without chronic pelvic pain were given 20 mg Melatonin or placebo orally daily for two consecutive menstrual cycles or months. The level of pain was recorded daily on the 11-point numeric rating scale, a difference of 1.3 units was considered clinically significant. Clincaltrials.gov nr NCT03782740. Sixteen participants completed the study in the placebo group and 18 in the melatonin group. The difference in endometriosis-associated pain between the groups showed to be non-significant statistically as well as clinically, 2.9 (SD 1.9) in the melatonin group and 3.3 (SD 2.0) in the placebo group, p = 0.45. This randomized, double-blinded, placebo-controlled trial could not show that 20 mg of melatonin given orally at bedtime had better analgesic effect on endometriosis-associated pain compared with placebo. No adverse effects were observed.
Topics: Female; Humans; Infant; Endometriosis; Melatonin; Pain Management; Pelvic Pain; Analgesics; Adjuvants, Pharmaceutic; Double-Blind Method; Dysmenorrhea; Treatment Outcome
PubMed: 37267394
DOI: 10.1371/journal.pone.0286182 -
Vaccine Nov 2021Adjuvants are essential for ensuring the efficacy of modern vaccines. Considering frequent local and systemic adverse reactions, research into the development of safer... (Review)
Review
Adjuvants are essential for ensuring the efficacy of modern vaccines. Considering frequent local and systemic adverse reactions, research into the development of safer and more effective adjuvants is being actively conducted. In recent years, the novel concept of laser vaccine adjuvants, which use the physical energy of light, has been developed. For long, light has been known to affect the physiological functions in living organisms. Since the development of lasers as stable light sources, laser adjuvants have evolved explosively in multiple ways over recent decades. Future laser adjuvants would have the potential not only to enhance the efficacy of conventional vaccine preparations but also to salvage candidate vaccines abandoned during development because of insufficient immunogenicity or owing to their inability to be combined with conventional adjuvants. Furthermore, the safety and efficacy of non-invasive laser adjuvants make them advantageous for vaccine dose sparing, which would be favorable for the timely and equitable global distribution of vaccines. In this review, we first describe the basics of light-tissue interactions, and then summarize the classification of lasers, the history of laser adjuvants, and the mechanisms by which different lasers elicit an immune response.
Topics: Adjuvants, Immunologic; Adjuvants, Vaccine; Immunity; Lasers; Vaccines
PubMed: 34666921
DOI: 10.1016/j.vaccine.2021.09.042 -
Scientific Reports Sep 2023Ewing sarcoma (EWS) is a malignant tumor arising in bone or soft tissue that occurs in adolescent and young adult patients as well as adults later in life. Although...
Ewing sarcoma (EWS) is a malignant tumor arising in bone or soft tissue that occurs in adolescent and young adult patients as well as adults later in life. Although non-metastatic EWS is typically responsive to treatment when newly diagnosed, relapsed cases have an unmet need for which no standard treatment approach exists. Recent phase III clinical trials for EWS comparing 7 vs 5 chemotherapy drugs have failed to improve survival. To extend the durability of remission for EWS, we investigated 3 non-chemotherapy adjuvant therapy drug candidates to be combined with chemotherapy. The efficacy of these adjuvant drugs was investigated via anchorage-dependent growth assays, anchorage-independent soft-agar colony formation assays and EWS xenograft mouse models. Enoxacin and entinostat were the most effective adjuvant drug in both long-term in vitro and in vivo adjuvant studies. In the context that enoxacin is an FDA-approved antibiotic, and that entinostat is an investigational agent not yet FDA-approved, we propose enoxacin as an adjuvant drug for further preclinical and clinical investigation in EWS patients.
Topics: Humans; Animals; Mice; Sarcoma, Ewing; Enoxacin; Neuroectodermal Tumors, Primitive, Peripheral; Benzamides; Adjuvants, Immunologic; Adjuvants, Pharmaceutic; Disease Models, Animal; Tumor Suppressor Protein p53
PubMed: 37658148
DOI: 10.1038/s41598-023-40751-z -
Frontiers in Immunology 2023Respiratory infections are a major public health concern caused by pathogens that colonize and invade the respiratory mucosal surface. Nasal vaccines have the advantage... (Review)
Review
Respiratory infections are a major public health concern caused by pathogens that colonize and invade the respiratory mucosal surface. Nasal vaccines have the advantage of providing protection at the primary site of pathogen infection, as they induce higher levels of mucosal secretory IgA antibodies and antigen-specific T and B cell responses. Adjuvants are crucial components of vaccine formulation that enhance the immunogenicity of the antigen to confer long-term and effective protection. Saponins, natural glycosides derived from plants, shown potential as vaccine adjuvants, as they can activate the mammalian immune system. Several licensed human vaccines containing saponins-based adjuvants administrated through intramuscular injection have demonstrated good efficacy and safety. Increasing evidence suggests that saponins can also be used as adjuvants for nasal vaccines, owing to their safety profile and potential to augment immune response. In this review, we will discuss the structure-activity-relationship of saponins, their important role in nasal vaccines, and future prospects for improving their efficacy and application in nasal vaccine for respiratory infection.
Topics: Humans; Adjuvants, Vaccine; Respiratory Tract Infections; Saponins; Vaccination; Vaccines
PubMed: 37020548
DOI: 10.3389/fimmu.2023.1153042 -
Journal of Ethnopharmacology Dec 2023Compound Kushen (Sophora flavescens Aiton) Injection (CKI) is a Chinese herbal injection made from extracts of Kushen and Baituling (Heterosmilax japonica Kunth),... (Review)
Review
ETHNOPHARMACOLOGICAL RELEVANCE
Compound Kushen (Sophora flavescens Aiton) Injection (CKI) is a Chinese herbal injection made from extracts of Kushen and Baituling (Heterosmilax japonica Kunth), containing matrine (MAT), oxymatrine (OMT) and other alkaloids with significant anti-tumor activity, and is widely used as an adjuvant treatment for cancer in China.
AIM OF THE STUDY
The existing systematic reviews/meta-analyses (SRs/MAs) were re-evaluated to provide a reference for the clinical application of CKI.
MATERIALS AND METHODS
SRs/MAs of CKI adjuvant therapy for cancer-related diseases were searched in four English language databases: PubMed, Embase, Web of Science, and Cochrane Library, all from the time of database construction to October 2022. 5 researchers independently conducted literature search and identification according to the inclusion criteria, and the data of the final literature were independently extracted, and finally the AMSTAR 2 tool, PRISMA statement and GRADE classification were used to evaluate the methodological quality of the included SRs/MAs, the degree of completeness of reporting and the quality of evidence for outcome indicators. Database registration: PROSPERO ID:CRD42022361349.
RESULTS
Eighteen SRs/MAs were finally included, with studies covering non-small cell lung cancer, primary liver cancer, gastric cancer, colorectal cancer, breast cancer, head and neck tumors, and cancer-related bone pain. The evaluation showed that the methodological quality of the included literature was extremely low, but most of the literature reported relatively complete entries; nine clinical effectiveness indicators for non-small cell lung cancer and digestive system tumors were rated as moderate in the GRADE quality of evidence, and the quality of other outcomes was low to very low.
CONCLUSION
CKI is a potentially effective drug for the adjuvant treatment of neoplastic diseases and may be more convincing for the adjuvant treatment of non-small cell lung cancer and digestive system tumors; however, due to the low methodological and evidentiary quality of the current SRs, their effectiveness needs to be confirmed by more high-quality evidence-based medical evidence.
Topics: Humans; Adjuvants, Immunologic; Adjuvants, Pharmaceutic; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Drugs, Chinese Herbal; Lung Neoplasms; Systematic Reviews as Topic
PubMed: 37328082
DOI: 10.1016/j.jep.2023.116778 -
Biomaterials Science Jul 2022Vaccination is a proven way to protect individuals against many infectious diseases, as currently highlighted in the global COVID-19 pandemic. Peptides- or small... (Review)
Review
Vaccination is a proven way to protect individuals against many infectious diseases, as currently highlighted in the global COVID-19 pandemic. Peptides- or small molecule antigen-based vaccination offer advantages over the classical vaccine approaches. However, peptides or small molecules by themselves are generally not sufficiently immunogenic, and thus require an adjuvant to boost an immune response. Several conjugated systems have been developed in recent years to overcome this obstacle. This review summarises different moieties which, when conjugated to peptide antigens, facilitate a specific immune response. Different classes of self-adjuvant moieties are reviewed, including self-assembly peptides, lipids, glycolipids, and polymers.
Topics: Adjuvants, Immunologic; Adjuvants, Pharmaceutic; Antigens; COVID-19; Humans; Pandemics; Peptides; Vaccine Development
PubMed: 35708540
DOI: 10.1039/d2bm00061j -
Frontiers in Immunology 2023Bacterial vaginosis (BV) is a common infection of the lower genital tract with a vaginal microbiome dysbiosis caused by decreasing of lactobacilli. Previous studies... (Randomized Controlled Trial)
Randomized Controlled Trial
UNLABELLED
Bacterial vaginosis (BV) is a common infection of the lower genital tract with a vaginal microbiome dysbiosis caused by decreasing of lactobacilli. Previous studies suggested that supplementation with live may benefit the recovery of BV, however, the outcomes vary in people from different regions. Herein, we aim to evaluate the effectiveness of oral Chinese-origin with adjuvant metronidazole (MET) on treating Chinese BV patients. In total, 67 Chinese women with BV were enrolled in this parallel controlled trial and randomly assigned to two study groups: a control group treated with MET vaginal suppositories for 7 days and a probiotic group treated with oral TM13 and LG55 as an adjuvant to MET for 30 days. By comparing the participants with Nugent Scores ≥ 7 and < 7 on days 14, 30, and 90, we found that oral administration of probiotics did not improve BV cure rates (72.73% and 84.00% at day 14, 57.14% and 60.00% at day 30, 32.14% and 48.39% at day 90 for probiotic and control group respectively). However, the probiotics were effective in restoring vaginal health after cure by showing higher proportion of participants with Nugent Scores < 4 in the probiotic group compared to the control group (87.50% and 71.43% on day 14, 93.75% and 88.89% on day 30, and 77.78% and 66.67% on day 90). The relative abundance of the probiotic strains was significantly increased in the intestinal microbiome of the probiotic group compared to the control group at day 14, but no significance was detected after 30 and 90 days. Also, the probiotics were not detected in vaginal microbiome, suggesting that TM13 and LG55 mainly acted through the intestine. A higher abundance of at baseline was significantly associated with long-term cure failure of BV and greatly contributed to the enrichment of the lipid IVA synthesis pathway, which could aggravate inflammation response. To sum up, TM13 and LG55 can restore the vaginal health of patients recovering from BV, and individualized intervention mode should be developed to restore the vaginal health of patients recovering from BV.
CLINICAL TRIAL REGISTRATION
https://classic.clinicaltrials.gov/ct2/show/, identifier NCT04771728.
Topics: Female; Humans; Adjuvants, Immunologic; Adjuvants, Pharmaceutic; Lactobacillus; Lactobacillus crispatus; Lactobacillus gasseri; Metronidazole; Treatment Outcome; Vagina; Vaginosis, Bacterial
PubMed: 37575226
DOI: 10.3389/fimmu.2023.1125239 -
Scientific Reports Sep 2023Upregulation of neuroplasticity might help maximize stroke recovery. One intervention that appears worthy of investigation is aerobic exercise. This study aimed to... (Randomized Controlled Trial)
Randomized Controlled Trial
Upregulation of neuroplasticity might help maximize stroke recovery. One intervention that appears worthy of investigation is aerobic exercise. This study aimed to determine whether a single bout of moderate intensity aerobic exercise can enhance neuroplasticity in people with stroke. Participants were randomly assigned (1:1) to a 20-min moderate intensity exercise intervention or remained sedentary (control). Transcranial magnetic stimulation measured corticospinal excitability of the contralesional hemisphere by recording motor evoked potentials (MEPs). Intermittent Theta Burst Stimulation (iTBS) was used to repetitively activate synapses in the contralesional primary motor cortex, initiating the early stages of neuroplasticity and increasing excitability. It was surmised that if exercise increased neuroplasticity, there would be a greater facilitation of MEPs following iTBS. Thirty-three people with stroke participated in this study (aged 63.87 ± 10.30 years, 20 male, 6.13 ± 4.33 years since stroke). There was an interaction between Time*Group on MEP amplitudes (P = 0.009). Participants allocated to aerobic exercise had a stronger increase in MEP amplitude following iTBS. A non-significant trend indicated time since stroke might moderate this interaction (P = 0.055). Exploratory analysis suggested participants who were 2-7.5 years post stroke had a strong MEP facilitation following iTBS (P < 0.001). There was no effect of age, sex, resting motor threshold, self-reported physical activity levels, lesion volume or weighted lesion load (all P > 0.208). Moderate intensity cycling may enhance neuroplasticity in people with stroke. This therapy adjuvant could provide opportunities to maximize stroke recovery.
Topics: Humans; Male; Animals; Adjuvants, Immunologic; Adjuvants, Pharmaceutic; Bicycling; Exercise; Gastropoda; Neuronal Plasticity; Stroke
PubMed: 37660093
DOI: 10.1038/s41598-023-40902-2 -
Journal of the American Geriatrics... Apr 2020The adjuvant analgesics are a large and diverse group of drugs that were developed for primary indications other than pain and are potentially useful analgesics for one... (Review)
Review
The adjuvant analgesics are a large and diverse group of drugs that were developed for primary indications other than pain and are potentially useful analgesics for one or more painful conditions. The "adjuvant" designation reflects their early use as opioid co-analgesics for cancer pain. During the past 3 decades, their role in pain management has changed with the advent of many new entities, emerging data from numerous analgesic trials, and growing clinical experience. Many of these drugs are now used as primary analgesics for specific types of chronic pain. With proper patient selection and cautious administration, they can potentially contribute meaningfully to the management of chronic pain in older adults. A practical approach categorizes the many adjuvant analgesics by broad indications: multipurpose drugs and drugs that target neuropathic pain, musculoskeletal pain, and cancer pain, respectively. This article reviews the status of the evidence supporting the analgesic potential of the adjuvant analgesics and discusses best practices in terms of drug selection and dosing. J Am Geriatr Soc 68:691-698, 2020.
Topics: Adjuvants, Pharmaceutic; Aged; Analgesics; Cancer Pain; Chronic Pain; Humans; Musculoskeletal Pain; Neuralgia; Pain Management
PubMed: 32216151
DOI: 10.1111/jgs.16340 -
Theranostics 2023Glioblastoma multiforme (GBM) is the most common and lethal type of adult brain cancer. Current GBM standard of care, including radiotherapy, often ends up with cancer...
Glioblastoma multiforme (GBM) is the most common and lethal type of adult brain cancer. Current GBM standard of care, including radiotherapy, often ends up with cancer recurrence, resulting in limited long-term survival benefits for GBM patients. Immunotherapy, such as immune checkpoint blockade (ICB), has thus far shown limited clinical benefit for GBM patients. Therapeutic vaccines hold great potential to elicit anti-cancer adaptive immunity, which can be synergistically combined with ICB and radiotherapy. Peptide vaccines are attractive for their ease of manufacturing and stability, but their therapeutic efficacy has been limited due to poor vaccine co-delivery and the limited ability of monovalent antigen vaccines to prevent tumor immune evasion. To address these challenges, here, we report GBM radioimmunotherapy that combines radiotherapy, ICB, and multivalent lymph-node-targeting adjuvant/antigen-codelivering albumin-binding vaccines (AAco-AlbiVax). Specifically, to codeliver peptide neoantigens and adjuvant CpG to lymph nodes (LNs), we developed AAco-AlbiVax based on a Y-shaped DNA scaffold that was site-specifically conjugated with CpG, peptide neoantigens, and albumin-binding maleimide-modified Evans blue derivative (MEB). As a result, these vaccines elicited antitumor immunity including neoantigen-specific CD8 T cell responses in mice. In orthotopic GBM mice, the combination of AAco-AlbiVax, ICB, and fractionated radiation enhanced GBM therapeutic efficacy. However, radioimmunotherapy only trended more efficacious over radiotherapy alone. Taken together, these studies underscore the great potential of radioimmunotherapy for GBM, and future optimization of treatment dosing and scheduling would improve the therapeutic efficacy.
Topics: Animals; Mice; Glioblastoma; Radioimmunotherapy; Neoplasm Recurrence, Local; Adjuvants, Immunologic; Adjuvants, Pharmaceutic; Vaccines; Albumins; Lymph Nodes
PubMed: 37649594
DOI: 10.7150/thno.84443