-
Current Pharmaceutical Biotechnology Jan 2024Ischemia-reperfusion injury (IRI) is a well-known ailment that can disturb organ function.
BACKGROUND
Ischemia-reperfusion injury (IRI) is a well-known ailment that can disturb organ function.
OBJECTIVES
This systematic review study investigated fisetin's effects and possible mechanisms in attenuating myocardial, cerebral, renal, and hepatic IRIs.
METHODS
This systematic review included studies earlier than Sep 2023 by following the PRISMA statement 2020. After determining inclusion and exclusion criteria and related keywords, bibliographic databases, such as Cochrane Library, PubMed, Web of Science, Embase, and Scopus databases, were used to search the relevant studies. Studies were imported in End- Note X8, and the primary information was recorded in Excel.
RESULTS
Fisetin reduced reactive oxygen species (ROS) generation and upregulated antioxidant enzymes, such as superoxide dismutase (SOD), glutathione (GSH), catalase (CAT), and glutathione peroxidase (GPx), in ischemic tissues. Moreover, fisetin can attenuate oxidative stress by activating phosphoinositide-3-kinase-protein kinase B/Akt (PI3K/Akt) and nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathways. Fisetin has been indicated to prevent the activation of several pro-inflammatory signaling pathways, including NF-κB (Nuclear factor kappa-light-chain-enhancer of activated B cells) and MAPKs (Mitogen-activated protein kinases). It also inhibits the production of pro-inflammatory cytokines and enzymes like tumor necrosis factor-a (TNF-α), inducible-NO synthase (iNOS), cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), interleukin-1β (IL-1β), IL-1, and IL-6. Fisetin attenuates IRI by improving mitochondrial function, anti-apoptotic effects, promoting autophagy, and preserving tissues from histological changes induced by IRIs.
CONCLUSION
Fisetin, by antioxidant, anti-inflammatory, mitochondrial protection, promoting autophagy, and anti-apoptotic properties, can reduce cell injury due to myocardial, cerebral renal, and hepatic IRIs without any significant side effects.
PubMed: 38310454
DOI: 10.2174/0113892010281821240102105415 -
Journal of Cancer Research and Clinical... Jan 2024Human papilloma virus (HPV)-positive head and neck squamous cell carcinoma (HNSCC) displays distinct epidemiological, clinical, and molecular characteristics compared to... (Review)
Review
PURPOSE
Human papilloma virus (HPV)-positive head and neck squamous cell carcinoma (HNSCC) displays distinct epidemiological, clinical, and molecular characteristics compared to the negative counterpart. Alterations in autophagy play an important role in cancer, and emerging evidence indicates an interplay of autophagy in HNSCC carcinogenesis and tumor promotion. However, the influence of HPV infection on autophagy in HNSCC has received less attention and has not been previously reviewed. Therefore, we here aimed to systematically review the role of autophagy explicitly in HPV HNSCC.
METHODS
Studies accessible in PubMed, Embase, Scopus, and Web of Science investigating HNSCC, highlighting the molecular biological differences between HPV and HPV HNSCC and its influences on autophagy in HNSCC were analyzed according to the PRISMA statement. A total of 10 articles were identified, included, and summarized.
RESULTS
The HPV16 E7 oncoprotein was reported to be involved in the degradation of AMBRA1 and STING, and to enhance chemotherapy-induced cell death via lethal mitophagy in HNSCC cells. Autophagy-associated gene signatures correlated with HPV-subtype and overall survival. Additionally, immunohistochemical (IHC) analyses indicate that high LC3B expression correlates with poor overall survival in oropharyngeal HNSCC patients.
CONCLUSION
HPV may dampen general bulk autophagic flux via degradation of AMBRA1 but may promote selective autophagic degradation of STING and mitochondria. Interpretations of correlations between autophagy-associated gene expressions or IHC analyses of autophagy-related (ATG) proteins in paraffin embedded tissue with clinicopathological features without biological validation need to be taken with caution.
Topics: Humans; Squamous Cell Carcinoma of Head and Neck; Papillomavirus Infections; Head and Neck Neoplasms; Carcinoma, Squamous Cell; Autophagy; Adaptor Proteins, Signal Transducing
PubMed: 38291202
DOI: 10.1007/s00432-023-05514-3 -
International Journal of Molecular... Jan 2024The social burden of dementia is remarkable since it affects some 57.4 million people all over the world. Impairment of autophagy in age-related diseases, such as... (Review)
Review
The social burden of dementia is remarkable since it affects some 57.4 million people all over the world. Impairment of autophagy in age-related diseases, such as dementia, deserves deep investigation for the detection of novel disease-modifying approaches. Several drugs belonging to different classes were suggested to be effective in managing Alzheimer's disease (AD) by means of autophagy induction. Useful autophagy inducers in AD should be endowed with a direct, measurable effect on autophagy, have a safe tolerability profile, and have the capability to cross the blood-brain barrier, at least with poor penetration. According to the PRISMA 2020 recommendations, we propose here a systematic review to appraise the measurable effectiveness of autophagy inducers in the improvement of cognitive decline and neuropsychiatric symptoms in clinical trials and retrospective studies. The systematic search retrieved 3067 records, 10 of which met the eligibility criteria. The outcomes most influenced by the treatment were cognition and executive functioning, pointing at a role for metformin, resveratrol, masitinib and TPI-287, with an overall tolerable safety profile. Differences in sample power, intervention, patients enrolled, assessment, and measure of outcomes prevents generalization of results. Moreover, the domain of behavioral symptoms was found to be less investigated, thus prompting new prospective studies with homogeneous design. PROSPERO registration: CRD42023393456.
Topics: Humans; Alzheimer Disease; Cognition; Cognitive Dysfunction; Prospective Studies; Retrospective Studies; Autophagy; Neurodegenerative Diseases
PubMed: 38279266
DOI: 10.3390/ijms25021264 -
Current Pharmaceutical Design 2023Artemisinin (ART) has been found to exert anti-tumor activity by regulating the cell cycle, inducing apoptosis, inhibiting angiogenesis and tumor invasion and...
Artemisinin (ART) has been found to exert anti-tumor activity by regulating the cell cycle, inducing apoptosis, inhibiting angiogenesis and tumor invasion and metastasis. Its derivatives (ARTs) can regulate the expression of drug-resistant proteins and reverse the multidrug resistance (MDR) of tumor cells by inhibiting intracellular drug efflux, inducing apoptosis and autophagy of tumor cells, thus enhancing the sensitivity of tumor cells to chemotherapy and radiotherapy. Recent studies have shown that nanodrugs play an important role in the diagnosis and treatment of cancer, which can effectively solve the shortcomings of poor hydrophilicity and low bioavailability of ARTs in the human body, prolong the in vivo circulation time, improve the targeting of drugs (including tumor tissues or specific organelles), and control the release of drugs in target tissues, thereby reducing the side effect. This review systematically summarized the latest research progress of nano-strategies of ARTs to enhance the efficiency of MDR reversal in breast cancer (BC) from the following two aspects: (1) Chemicals encapsulated in nanomaterials based on innovative anti-proliferation mechanism: non-ABC transporter receptor candidate related to ferroptosis (dihydroartemisinin/DHA analogs). (2) Combination therapy strategy of nanomedicine (drug-drug combination therapy, drug-gene combination, and chemical-physical therapy). Self-assembled nano-delivery systems enhance therapeutic efficacy through increased drug loading, rapid reactive release, optimized delivery sequence, and realization of cascade-increasing effects. New nanotechnology methods must be designed for specific delivery routines to achieve targeting administration and overcome MDR without affecting normal cells. The significance of this review is to expect that ART and ARTs can be widely used in clinical practice. In the future, nanotechnology can help people to treat multidrug resistance of breast cancer more accurately and efficiently.
Topics: Female; Humans; Artemisinins; Breast Neoplasms; Drug Resistance, Multiple; Drug Therapy, Combination
PubMed: 38270162
DOI: 10.2174/0113816128282248231205105408 -
Frontiers in Pharmacology 2023Recently, multiple preclinical studies have reported the beneficial effect of berberine in the treatment of Alzheimer's disease (AD). Nevertheless, the neuroprotective...
Recently, multiple preclinical studies have reported the beneficial effect of berberine in the treatment of Alzheimer's disease (AD). Nevertheless, the neuroprotective effects and possible mechanisms of berberine against AD are not universally recognized. This study aimed to conduct a systematic review and meta-analysis by integrating relevant animal studies to assess the neuroprotective effects and potential mechanisms of berberine on AD. We systematically searched PubMed, Embase, Scopus and Web of Science databases that reported the effects of berberine on AD models up to 1 February 2023. The escape latency, times of crossing platform, time spent in the target quadrant and pro-oligomerized amyloid beta 42 (Aβ) were included as primary outcomes. The secondary outcomes were the Tau-ps 204, Tau-ps 404, β-site of APP cleaving enzyme (BACE1), amyloid precursor protein (APP), acetylcholine esterase (AChE), tumor necrosis factor ⍺ (TNF-α), interleukin 1β (IL-1β), IL-6, nitric oxide (NO), glial fibrillary acidic protein (GFAP), malonaldehyde (MDA), glutathione S-transferase (GST), glutathione (GSH), glutathione peroxidase (GPx), Beclin-1 and neuronal apoptosis cells. This meta-analysis was conducted using RevMan 5.4 and STATA 15.1. The SYRCLE's risk of bias tool was used to assess the methodological quality. Twenty-two studies and 453 animals were included in the analysis. The overall results showed that berberine significantly shortened the escape latency ( < 0.00001), increased times of crossing platform ( < 0.00001) and time spent in the target quadrant ( < 0.00001), decreased Aβ deposition ( < 0.00001), Tau-ps 202 ( < 0.00001) and Tau-ps 404 ( = 0.002), and improved BACE1, APP, AChE, Beclin-1, neuronal apoptosis cells, oxidative stress and inflammation levels. Berberine may be a promising drug for the treatment of AD based on preclinical evidence (especially when the dose was 5-260 mg/kg). The potential mechanisms for these protective effects may be closely related to anti-neuroinflammation, anti-oxidative stress, modulation of autophagy, inhibition of neuronal apoptosis and protection of cholinergic system. However, these results may be limited by the quality of existing research. Larger and methodologically more rigorous preclinical research are needed to provide more convincing evidence.
PubMed: 38259291
DOI: 10.3389/fphar.2023.1287750 -
Pathogens (Basel, Switzerland) Dec 2023is an intracellular bacillus that causes leprosy, a neglected disease that affects macrophages and Schwann cells. Leprosy reactions are acute inflammatory responses to... (Review)
Review
BACKGROUND
is an intracellular bacillus that causes leprosy, a neglected disease that affects macrophages and Schwann cells. Leprosy reactions are acute inflammatory responses to mycobacterial antigens, classified as type1 (T1R), a predominant cellular immune response, or type2 (T2R), a humoral phenomenon, leading to a high number of bacilli in infected cells and nerve structures. Xenophagy is a type of selective autophagy that targets intracellular bacteria for lysosomal degradation; however, its immune mechanisms during leprosy reactions are still unclear. This review summarizes the relationship between the autophagic process and elimination during leprosy reactions.
METHODS
Three databases, PubMed/Medline (n = 91), Scopus (n = 73), and ScienceDirect (n = 124), were searched. After applying the eligibility criteria, articles were selected for independent peer reviewers in August 2023.
RESULTS
From a total of 288 studies retrieved, eight were included. In multibacillary (MB) patients who progressed to T1R, xenophagy blockade and increased inflammasome activation were observed, with IL-1β secretion before the reactional episode occurrence. On the other hand, recent data actually observed increased IL-15 levels before the reaction began, as well as IFN-γ production and xenophagy induction.
CONCLUSION
Our search results showed a dichotomy in the T1R development and their relationship with xenophagy. No T2R studies were found.
PubMed: 38133338
DOI: 10.3390/pathogens12121455 -
Biomedicine & Pharmacotherapy =... Jan 2024Development of therapeutic agents that have fewer adverse effects and have higher efficacy for diseases, such as cancer, metabolic disorders, neurological diseases,... (Review)
Review
Development of therapeutic agents that have fewer adverse effects and have higher efficacy for diseases, such as cancer, metabolic disorders, neurological diseases, infections, cardiovascular diseases, and respiratory diseases, are required. Recent studies have focused on identifying novel sources for pharmaceutical molecules to develop therapies against these diseases. Among the sources for potentially new therapies, animal venom-derived molecules have generated much interest. Various animal venom-derived proteins and peptides have been isolated, identified, synthesized, and tested to develop drugs. Venom-derived peptides have several biomedical properties, such as proapoptotic, cell migration, and autophagy regulation activities in cancer cell models; induction of vasodilation by nitric oxide and regulation of angiotensin II; modification of insulin response by controlling calcium and potassium channels; regulation of pain receptor activity; modulation of immune cell activity; alteration of motor neuron activity; degradation or inhibition of β-amyloid plaque formation; antibacterial, antifungal, antiviral, and antiprotozoal activities; increase in sperm motility and potentiation of erectile function; reduction of intraocular pressure; anticoagulation, fibrinolytic, and antithrombotic activities; etc. This systematic review compiles these biomedical properties and potential biomedical applications of synthesized animal venom-derived peptides reported in the latest research. In addition, the limitations and areas of opportunity in this research field are discussed so that new studies can be developed based on the data presented.
Topics: Animals; Male; Venoms; Sperm Motility; Peptides; Angiotensin II
PubMed: 38113629
DOI: 10.1016/j.biopha.2023.116015 -
Cancer Letters Feb 2024Cancer is considered as the second leading cause of mortality, and cancer incidence is still growing rapidly worldwide, which poses an increasing global health burden.... (Review)
Review
Cancer is considered as the second leading cause of mortality, and cancer incidence is still growing rapidly worldwide, which poses an increasing global health burden. Although chemotherapy is the most widely used treatment for cancer, its effectiveness is limited by drug resistance and severe side effects. Mitophagy is the principal mechanism that degrades damaged mitochondria via the autophagy/lysosome pathway to maintain mitochondrial homeostasis. Emerging evidence indicates that mitophagy plays crucial roles in tumorigenesis, particularly in cancer therapy. Mitophagy can exhibit dual effects in cancer, with both cancer-inhibiting or cancer-promoting function in a context-dependent manner. A variety of natural compounds have been found to affect cancer cell death and display anticancer properties by modulating mitophagy. In this review, we provide a systematic overview of mitophagy signaling pathways, and examine recent advances in the utilization of natural compounds for cancer therapy through the modulation of mitophagy. Furthermore, we address the inquiries and challenges associated with ongoing investigations concerning the application of natural compounds in cancer therapy based on mitophagy. Overcoming these limitations will provide opportunities to develop novel interventional strategies for cancer treatment.
Topics: Humans; Autophagy; Cell Death; Mitochondria; Mitophagy; Neoplasms
PubMed: 38097131
DOI: 10.1016/j.canlet.2023.216590 -
Frontiers in Cardiovascular Medicine 2023Recently, attention has been paid to the protective properties of active ingredients in (AISM) against organ toxicity induced by chemotherapy drugs. Purpose of the... (Review)
Review
BACKGROUND
Recently, attention has been paid to the protective properties of active ingredients in (AISM) against organ toxicity induced by chemotherapy drugs. Purpose of the present systematic review is to evaluate the chemoprotective effects and mechanisms of AISM on models of doxorubicin-induced cardiotoxicity (DIC).
METHODS
According to the PRISMA guideline, the current systematic review was conducted in the Web of Science, PubMed, Embase, and the Cochrane Library to collect all relevant studies on "the role of AISM on DIC" published up until May 2023. The SYRCLE's tool was used to identify potential risk of bias.
RESULTS
Twenty-two eligible articles were included in this systematic review. Eleven types of active ingredients in were used for DIC, which have the following effects: improvement of physical signs and biochemical indicators, reduction of cardiac function damage caused by DIC, protection of heart tissue structure, enhancement of myocardial cell viability, prevention of cardiomyocyte apoptosis, increase of the chemosensitivity of cancer cells to Doxorubicin, . The cardioprotective mechanism of AISM involves inhibiting apoptosis, attenuating oxidative stress, suppressing endoplasmic reticulum (ER) stress, decreasing inflammation, improving mitochondrial structure and function, affecting cellular autophagy and calcium homeostasis. The quality scores of included studies ranged from 4 to 7 points (a total of 10 points), according to SYRCLE's risk of bias tool.
CONCLUSION
This systematic review demonstrated that AISM have chemoprotective effects on DIC and models through several main mechanisms such as anti-apoptosis, antioxidant effects, anti-ER stress, and anti-inflammatory.
PubMed: 37915739
DOI: 10.3389/fcvm.2023.1267525 -
Frontiers in Neuroscience 2023Spinal cord injury (SCI) is a catastrophic condition with few therapeutic options. Astaxanthin (AST), a natural nutritional supplement with powerful antioxidant...
Spinal cord injury (SCI) is a catastrophic condition with few therapeutic options. Astaxanthin (AST), a natural nutritional supplement with powerful antioxidant activities, is finding its new application in the field of SCI. Here, we performed a systematic review to assess the neurological roles of AST in rats following SCI, and assessed the potential for clinical translation. Searches were conducted on PubMed, Embase, Cochrane Library, the Web of Science, China National Knowledge Infrastructure, WanFang data, Vip Journal Integration Platform, and SinoMed databases. Animal studies that evaluated the neurobiological roles of AST in a rat model of SCI were included. A total of 10 articles were included; most of them had moderate-to-high methodological quality, while the overall quality of evidence was not high. Generally, the meta-analyses revealed that rats treated with AST exhibited an increased Basso, Beattie, and Bresnahan (BBB) score compared with the controls, and the weighted mean differences (WMDs) between those two groups showed a gradual upward trend from days 7 (six studies, n = 88, WMD = 2.85, 95% CI = 1.83 to 3.87, < 0.00001) to days 28 (five studies, n = 76, WMD = 6.42, 95% CI = 4.29 to 8.55, < 0.00001) after treatment. AST treatment was associated with improved outcomes in spared white matter area, motor neuron survival, and SOD and MDA levels. Subgroup analyses indicated there were differences in the improvement of BBB scores between distinct injury types. The trial sequential analysis then firmly proved that AST could facilitate the locomotor recovery of rats following SCI. In addition, this review suggested that AST could modulate oxidative stress, neuroinflammation, neuron loss, and autophagy multiple signaling pathways for treating SCI. Collectively, with a protective effect, good safety, and a systematic action mechanism, AST is a promising candidate for future clinical trials of SCI. Nonetheless, in light of the limitations of the included studies, larger and high-quality studies are needed for verification.
PubMed: 37881327
DOI: 10.3389/fnins.2023.1255755