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1.
Trends Biochem Sci ; 2024 May 06.
Article in English | MEDLINE | ID: mdl-38714376

ABSTRACT

Protein lipoylation, a crucial post-translational modification (PTM), plays a pivotal role in mitochondrial function and emerges as a key player in cell death through cuproptosis. This novel copper-driven cell death pathway is activated by excessive copper ions binding to lipoylated mitochondrial proteins, disrupting energy production and causing lethal protein aggregation and cell death. The intricate relationship among protein lipoylation, cellular energy metabolism, and cuproptosis offers a promising avenue for regulating essential cellular functions. This review focuses on the mechanisms of lipoylation and its significant impact on cell metabolism and cuproptosis, emphasizing the key genes involved and their implications for human diseases. It offers valuable insights into targeting dysregulated cellular metabolism for therapeutic purposes.

2.
Int J Surg ; 2024 May 03.
Article in English | MEDLINE | ID: mdl-38701514

ABSTRACT

BACKGROUND: Ageing population is a worldwide phenomenon with correspondingly higher proportion of older patients being treated in the hospital setting. Sarcopenia, which increases with age, has serious negative implications on health, hospitalization and overall postoperative recovery. There is no mutual consensus on perioperative management of sarcopenia in surgical patients in Singapore. The purpose of this study is to create greater clarity pertaining to the recognition of sarcopenia, the application of assessment criteria of sarcopenia and perioperative management of surgical patients in Singapore. METHODS: A modified Delphi consensus consisting of a panel of experts from Singapore forming a multidisciplinary team, including surgeons, geriatricians, anesthesiologists, physiotherapists and dieticians. Eight recommendations were proposed by the steering committee. Literature search from MEDLINE, Embase and Scopus for articles up till June 2023 were performed to support recommendation statements. The expert panel voted on agreement to recommendation statements and graded the level of evidence supporting each statement through surveys to achieve consensus, set at 85% a priori. RESULTS: The panelists underwent two rounds of anonymized, independent voting before reaching consensus for all eight statements. After the first round, seven statements reached consensus, including the corresponding grading for level of evidence. The statement which did not achieve consensus was revised with supporting literature and after the second round of survey, all eight statements and level of evidence reached consensus, completing the Delphi process. These eight statements covered themes to (1) encourage the identification of sarcopenia, (2) guide pre-operative and (3) post-operative management of sarcopenia. CONCLUSION: With the varying approaches in perioperative management, poor understanding of and identification of sarcopenia can result in suboptimal management of sarcopenia in surgical patients. Given the abundance of evidence linking beneficial impact on recovery and post-operative complications with prudent management of sarcopenia, it is imperative and urgent to achieve awareness and consensus.

3.
J Alzheimers Dis ; 99(1): 291-305, 2024.
Article in English | MEDLINE | ID: mdl-38669534

ABSTRACT

Background: The complement system plays crucial roles in cognitive impairment and acute ischemic stroke (AIS). High levels of complement proteins in plasma astrocyte-derived exosomes (ADEs) were proven to be associated with Alzheimer's disease. We aimed to investigate the relationship of complement proteins in serum ADEs with poststroke cognitive impairment in type 2 diabetes mellitus (T2DM) patients. Methods: This study analyzed 197 T2DM patients who suffered AIS. The Beijing version of the Montreal Cognitive Assessment (MoCA) was used to assess cognitive function. Complement proteins in serum ADEs were quantified using ELISA kits. Results: Mediation analyses showed that C5b-9 and C3b in serum ADEs partially mediate the impact of obstructive sleep apnea (OSA), depression, small vessel disease (SVD), and infarct volume on cognitive function at the acute phase of AIS in T2DM patients. After adjusting for age, sex, time, and interaction between time and complement proteins in serum ADEs, the mixed linear regression showed that C3b and complement protein Factor B in serum ADEs were associated with MoCA scores at three-, six-, and twelve-months after AIS in T2DM patients. Conclusions: Our study suggested that the impact of OSA, depression, SVD, and infarct volume on cognitive impairment in the acute stage of AIS may partially mediate through the complement proteins in serum ADEs. Additionally, the complement proteins in serum ADEs at the acute phase of AIS associated with MoCA scores at three-, six-, twelve months after AIS in T2DM patients.REGISTRATION: URL: http://www.chictr.org.cn/,ChiCTR1900021544.


Subject(s)
Astrocytes , Cognitive Dysfunction , Diabetes Mellitus, Type 2 , Exosomes , Humans , Male , Female , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/blood , Cognitive Dysfunction/blood , Cognitive Dysfunction/etiology , Exosomes/metabolism , Aged , Middle Aged , Astrocytes/metabolism , Complement System Proteins/metabolism , Ischemic Stroke/blood , Ischemic Stroke/complications , Ischemic Stroke/psychology , Stroke/blood , Stroke/complications , Stroke/psychology
4.
Poult Sci ; 103(6): 103728, 2024 Apr 03.
Article in English | MEDLINE | ID: mdl-38688194

ABSTRACT

E2F transcription factor 5 (E2F5) gene is a transcription factor, plays an important role in the development of a variety of cells. E2F5 is expressed in human and mouse adipocytes, but its specific function in adipogenesis is unclear. Krüppel-like factor 7 (KLF7) facilitates proliferation and inhibits differentiation in chicken preadipocytes. Our previous KLF7 chromatin immunoprecipitation-sequencing analysis revealed a KLF7-binding peak in the 3' flanking region of the E2F5, indicating a regulatory role of KLF7 in this region. In the present study, we investigated E2F5 potential role, the overexpression and knockdown analyses revealed that E2F5 inhibited the differentiation and promoted the proliferation of chicken preadipocytes. Moreover, we identified enhancer activity in the 3' flanking region (nucleotides +22661/+22900) of E2F5 and found that KLF7 overexpression increased E2F5 expression and luciferase activity in this region. Deleting the putative KLF7-binding site eliminated the promoting effect of KLF7 overexpression on E2F5 expression. Further, E2F5 reversed the KLF7-induced decrease in preadipocyte differentiation and increase in preadipocyte proliferation. Taken together, our findings demonstrate that KLF7 inhibits differentiation and promotes proliferation in preadipocytes by enhancing E2F5 transcription.

5.
World J Gastrointest Surg ; 16(3): 777-789, 2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38577068

ABSTRACT

BACKGROUND: Colorectal cancer is the third most common cancer and the second highest cause of cancer-related mortality worldwide. About 5%-10% of patients are diagnosed with locally advanced rectal cancer (LARC) on presentation. For LARC invading into other structures (i.e. T4b), multivisceral resection (MVR) and/or pelvic exenteration (PE) remains the only potential curative surgical treatment. MVR and/or PE is a major and complex surgery with high post-operative morbidity. Minimally invasive surgery (MIS) has been shown to improve short-term post-operative outcomes in other gastrointestinal malignancies, but there is little evidence on its use in MVR, especially so for robotic MVR. AIM: To assess the feasibility and safety of minimally invasive MVR (miMVR), and compare post-operative outcomes between robotic and laparoscopic MVR. METHODS: This is a single-center retrospective cohort study from 1st January 2015 to 31st March 2023. Inclusion criteria were patients diagnosed with cT4b rectal cancer and underwent MVR, or stage 4 disease with resectable systemic metastases. Patients who underwent curative MVR for locally recurrent rectal cancer, or metachronous rectal cancer were also included. Exclusion criteria were patients with systemic metastases with non-resectable disease. All patients planned for elective surgery were enrolled into the standard enhanced recovery after surgery pathway with standard peri-operative management for colorectal surgery. Complex surgery was defined based on technical difficulty of surgery (i.e. total PE, bladder-sparing prostatectomy, pelvic lymph node dissection or need for flap creation). Our primary outcomes were the margin status, and complication rates. Categorical values were described as percentages and analysed by the chi-square test. Continuous variables were expressed as median (range) and analysed by Mann-Whitney U test. Cumulative overall survival (OS) and recurrence-free survival (RFS) were analysed using Kaplan-Meier estimates with life table analysis. Log-rank test was performed to determine statistical significance between cumulative estimates. Statistical significance was defined as P < 0.05. RESULTS: A total of 46 patients were included in this study [open MVR (oMVR): 12 (26.1%), miMVR: 36 (73.9%)]. Patients' American Society of Anesthesiologists score, body mass index and co-morbidities were comparable between oMVR and miMVR. There is an increasing trend towards robotic MVR from 2015 to 2023. MiMVR was associated with lower estimated blood loss (EBL) (median 450 vs 1200 mL, P = 0.008), major morbidity (14.7% vs 50.0%, P = 0.014), post-operative intra-abdominal collections (11.8% vs 50.0%, P = 0.006), post-operative ileus (32.4% vs 66.7%, P = 0.04) and surgical site infection (11.8% vs 50.0%, P = 0.006) compared with oMVR. Length of stay was also shorter for miMVR compared with oMVR (median 10 vs 30 d, P = 0.001). Oncological outcomes-R0 resection, recurrence, OS and RFS were comparable between miMVR and oMVR. There was no 30-d mortality. More patients underwent robotic compared with laparoscopic MVR for complex cases (robotic 57.1% vs laparoscopic 7.7%, P = 0.004). The operating time was longer for robotic compared with laparoscopic MVR [robotic: 602 (400-900) min, laparoscopic: Median 455 (275-675) min, P < 0.001]. Incidence of R0 resection was similar (laparoscopic: 84.6% vs robotic: 76.2%, P = 0.555). Overall complication rates, major morbidity rates and 30-d readmission rates were similar between laparoscopic and robotic MVR. Interestingly, 3-year OS (robotic 83.1% vs 58.6%, P = 0.008) and RFS (robotic 72.9% vs 34.3%, P = 0.002) was superior for robotic compared with laparoscopic MVR. CONCLUSION: MiMVR had lower post-operative complications compared to oMVR. Robotic MVR was also safe, with acceptable post-operative complication rates. Prospective studies should be conducted to compare short-term and long-term outcomes between robotic vs laparoscopic MVR.

6.
Heliyon ; 10(7): e28312, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38571578

ABSTRACT

Hydropower stations that are part of the grid system frequently encounter challenges related to the uneven distribution of power generation and associated benefits, primarily stemming from delays in obtaining timely load data. This research addresses this issue by developing a scheduling model that combines power load prediction and dual-objective optimization. The practical application of this model is demonstrated in a real-case scenario, focusing on the Shatuo Hydropower Station in China. In contrast to current models, the suggested model can achieve optimal dispatch for grid-connected hydropower stations even when power load data is unavailable. Initially, the model assesses various prediction models for estimating power load and subsequently incorporates the predictions into the GA-NSGA-II algorithm, specifically an enhanced elite non-dominated sorting genetic algorithm. This integration is performed while considering the proposed objective functions to optimize the discharge flow of the hydropower station. The outcomes reveal that the CNN-GRU model, denoting Convolutional Neural Network-Gated Recursive Unit, exhibits the highest prediction accuracy, achieving R-squared and RMSE (i.e., Root Mean Square Error) values of 0.991 and 0.026, respectively. The variance between scheduling based on predicted load values and actual load values is minimal, staying within 5 (m3/s), showcasing practical effectiveness. The optimized scheduling outcomes in the real case study yield dual advantages, meeting both the demands of ship navigation and hydropower generation, thus achieving a harmonious balance between the two requirements. This approach addresses the real-world challenges associated with delayed load data collection and insufficient scheduling, offering an efficient solution for managing hydropower station scheduling to meet both power generation and navigation needs.

7.
Zootaxa ; 5415(1): 117-143, 2024 Feb 20.
Article in English | MEDLINE | ID: mdl-38480212

ABSTRACT

Recent collection in Panti Forest Reserve in Johor, Peninsular Malaysia offered us the opportunity to better understand the species in southern Malay Peninsula. Two new species and one new genus of Meconematini are described here: Cercoteratura reflexa sp. n. and Platycercotura caricauda gen. et sp. n. We present new locality records for Peracca macritchiensis Tan & Ingrisch, 2014, Viriacca viridis Ingrisch, 1998; Lipotactes (Dialipotactes) maculatus Hebard, 1922; Asiophlugis rete Gorochov, 1998; and Arnobia pilipes tropica Gorochov, 1998, all of which were previously recorded in Pahang (Peninsular Malaysia) and Singapore, suggest that the distribution of these species is continuous between Pahang and Singapore. New locality record for Asiophlugis temasek temasek Gorochov & Tan, 2011, previously known only from Singapore, indicates that this subspecies is no longer endemic to Singapore.


Subject(s)
Orthoptera , Animals , Malaysia , Animal Distribution
8.
Zootaxa ; 5410(2): 267-279, 2024 Feb 13.
Article in English | MEDLINE | ID: mdl-38480244

ABSTRACT

The taxonomy of the crickets from the genus Odontogryllodes Chopard, 1969 is reviewed. Two species new to science are described here, one from Peninsular Malaysia (part of Malay Peninsula) and another from East Malaysia (part of Borneo): Odontogryllodes undatus Tan, Muhammad & Abdullah sp. nov. from Panti Forest Reserve and Odontogryllodes magnus Tan, Japir & Chung sp. nov. from Tenompok Forest Reserve, respectively. We also present an updated key to the species of Odontogryllodes. In total, nine species are currently known.


Subject(s)
Gryllidae , Animals , Animal Distribution
9.
Zootaxa ; 5424(1): 61-79, 2024 Mar 12.
Article in English | MEDLINE | ID: mdl-38480300

ABSTRACT

A new species of Itara (Phormincter) is described from Mindanao in the Philippines: Itara (Phormincter) mindanao Tan, Grumo, Gono & Bahoy, sp. nov. This represents the first record of this subgenus in the Philippines, having previously known only from Borneo, Java, Malay Peninsula and Sumatra; as well as only the second species of Itara known from the Philippines and the first from Mindanao Island. The male calling song of the holotype was also recorded and is described here. Additionally, the male calling song of another congener, Itara (Singitara) singularis Gorochov, 1997 from Sabah, is described here. A new species of Itara (Bornitara) is also described from Sabah in Borneo: Itara (Bornitara) tenompok Tan, Japir & Chung, sp. nov.


Subject(s)
Orthoptera , Male , Animals , Malaysia , Philippines , Animal Distribution
10.
Zootaxa ; 5419(4): 584-600, 2024 Mar 08.
Article in English | MEDLINE | ID: mdl-38480307

ABSTRACT

Based on recent field sampling in the highlands of western Sabah, a new species of Depressacca Ingrisch, 1998 (Conocephalinae: Agraeciini) is described from Tenompok, Depressacca macrolima sp. nov., that can be easily distinguish from two other known congeners by the presence of numerous large and falcate spines on the legs numerous large and falcate spines on its legs. Based on the new material, we also document here the live images and/or new locality records for other katydids of the tribes Agraeciini and Meconematini: Bispinolakis longicauda Ingrisch, 1998, Palaeoagraecia philippina (Karny, 1926) and Salomona borneensis Willemse, 1959; Alloteratura (Meconemopsis) longa Gorochov, 2008, Borneratura kinabaluana (Bey-Bienko, 1971) and Rhinoteratura pulchra Gorochov, 2008.


Subject(s)
Orthoptera , Animals , Malaysia , Animal Distribution
11.
Heliyon ; 10(3): e24746, 2024 Feb 15.
Article in English | MEDLINE | ID: mdl-38318012

ABSTRACT

Objective: Half of the patients with acute large artery occlusion (LAO) have poor outcomes after endovascular treatment (EVT). Early complications such as cerebral edema and symptomatic intracranial hemorrhage (sICH) can lead to early neurological deterioration (END), which correlates with hemodynamics. This study aimed to identify the hemodynamic predictors of END and outcomes in LAO patients after EVT. Methods: A total of 76 patients with anterior circulation LAO who underwent EVT and received transcranial Doppler (TCD) monitoring were included. Bilateral middle cerebral artery (MCA) blood flow velocities (BFVs) were measured repeatedly within 1 week. Mean flow velocities (MFV) and MFV index (ipsilateral MFV/contralateral MFV) were calculated. The primary outcome was the incidence of END within 72 h. The secondary outcome was the functional outcome at 90 days-a good outcome was defined as a modified Rankin scale (mRS) score of 0-2, while a poor outcome was defined as an mRS score of 3-6. Results: A total of 13 patients (17.1 %) experienced END within 72 h, including 5 (38.5 %) with cerebral edema, 5 (38.5 %) with sICH, and 3 (23.0 %) with infarct progression. Multivariable logistic regression analysis showed that a higher 24 h MFV index was independently associated with END (aOR 10.5; 95 % CI 2.28-48.30, p = 0.003) and a poor 90-day outcome (aOR 5.10; 95 % CI 1.38-18.78, p = 0.014). The area under the receiver operating characteristic (ROC) curve (AUC) of the 24 h MFV index for predicting END was 0.807 (95 % CI 0.700-0.915, p = 0.0005), the sensitivity was 84.6 %, and the specificity was 66.7 %. At the 1-week TCD follow-up, patients who had poor 90-day outcomes showed significantly higher 1-week iMFV [73.5 (58.4-99.0) vs. 57.7 (45.3-76.3), p = 0.004] and MFV index [1.24 (0.98-1.57) vs.1.0 (0.87-1.15) p = 0.007]. A persistent high MFV index (PHMI) was independently associated with a poor outcome (aOR 7.77, 95 % CI 1.81-33.3, p = 0.006). Conclusion: TCD monitoring within 24 h after EVT in LAO patients can help predict END, while dynamic follow-up within 1 week is valuable in predicting clinical outcomes.

12.
ACS Nano ; 18(8): 6673-6689, 2024 Feb 27.
Article in English | MEDLINE | ID: mdl-38353701

ABSTRACT

The current live rotavirus (RV) vaccines show reduced effectiveness in developing countries, calling for vaccine strategies with improved efficacy and safety. We generated pseudovirus nanoparticles (PVNPs) that display multiple ectodomains of RV viral protein 4 (VP4), named S-VP4e, as a nonreplicating RV vaccine candidate. The RV spike protein VP4s that bind host receptors and facilitate viral entry are excellent targets for vaccination. In this study, we developed scalable methods to produce three S-VP4e PVNPs, each displaying the VP4e antigens from one of the three predominant P[8], P[4], and P[6] human RVs (HRVs). These PVNPs were recognized by selected neutralizing VP4-specific monoclonal antibodies, bound glycan receptors, attached to permissive HT-29 cells, and underwent cleavage by trypsin between VP8* and VP5*. 3D PVNP models were constructed to understand their structural features. A trivalent PVNP vaccine containing the three S-VP4e PVNPs elicited high and well-balanced VP4e-specific antibody titers in mice directed against the three predominant HRV P types. The resulting antisera neutralized the three HRV prototypes at high titers; greater than 4-fold higher than the neutralizing responses induced by a trivalent vaccine consisting of the S60-VP8* PVNPs. Finally, the trivalent S-VP4e PVNP vaccine provided 90-100% protection against diarrhea caused by HRV challenge. Our data supports the trivalent S-VP4e PVNPs as a promising nonreplicating HRV vaccine candidate for parenteral delivery to circumvent the suboptimal immunization issues of all present live HRV vaccines. The established PVNP-permissive cell and PVNP-glycan binding assays will be instrumental for further investigating HRV-host cell interactions and neutralizing effects of VP4-specific antibodies and antivirals.


Subject(s)
Rotavirus , Viral Vaccines , Animals , Mice , Humans , Nanovaccines , Viral Proteins/metabolism , Antibodies, Neutralizing , Polysaccharides , Immunity , Antibodies, Viral
13.
Nat Prod Res ; : 1-6, 2024 Feb 19.
Article in English | MEDLINE | ID: mdl-38372270

ABSTRACT

A new isopimarane-type diterpene clinacanoid A (1) together with seven known terpenoids (2-8) were obtained from the Clinacanthus nutans. Their structures were elucidated based on extensive spectroscopic analysis (NMR, HR-ESI-MS), and the absolute configuration of 1 was established based on single crystal X-ray diffraction. The inhibitory activity of all the compounds on NO production in lipopolysaccharide-induced (LPS) mouse leukemic monocyte macrophage RAW264.7 cells was evaluated. Among them, compounds 1 and 3 showed potential anti-inflammatory activities, with IC50 values of 13.3 ± 0.3 and 12.4 ± 0.4 µM, respectively.

14.
Genes (Basel) ; 15(2)2024 Feb 07.
Article in English | MEDLINE | ID: mdl-38397203

ABSTRACT

Carotid intima-media thickness (CIMT) is a surrogate indicator for atherosclerosis and has been shown to predict cardiovascular risk in multiple large studies. Identification of molecular markers for carotid atheroma plaque formation can be critical for early intervention and prevention of atherosclerosis. This study performed transcription factor (TF) network analysis of global gene expression data focusing on two TF genes, ZNF385D and HAND2, whose polymorphisms have been recently reported to show association with CIMT. Genome-wide gene expression data were measured from pieces of carotid endarterectomy collected from 34 hypertensive patients (atheroma plaque of stages IV and above according to the Stary classification) each paired with one sample of distant macroscopically intact tissue (stages I and II). Transcriptional regulation networks or the regulons were reconstructed for ZNF385D (5644 target genes) and HAND2 (781 target genes) using network inference. Their association with the progression of carotid atheroma was examined using gene-set enrichment analysis with extremely high statistical significance for regulons of both ZNF385D and HAND2 (p < 6.95 × 10-7) suggesting the involvement of expression quantitative loci (eQTL). Functional annotation of the regulon genes found heavy involvement in the immune system's response to inflammation and infection in the development of atherosclerosis. Detailed examination of the regulation and correlation patterns suggests that activities of the two TF genes could have high clinical and interventional impacts on impairing carotid atheroma plaque formation and preventing carotid atherosclerosis.


Subject(s)
Atherosclerosis , Carotid Artery Diseases , Plaque, Atherosclerotic , Humans , Plaque, Atherosclerotic/genetics , Transcription Factors/genetics , Carotid Intima-Media Thickness , Risk Factors , Carotid Artery Diseases/genetics , Gene Expression Regulation
15.
BMC Infect Dis ; 24(1): 20, 2024 Jan 02.
Article in English | MEDLINE | ID: mdl-38166673

ABSTRACT

BACKGROUND: Bacterial vaginosis (BV) is a widely occurring vaginal inflammation in women of childbearing age caused by dysbiosis of the vaginal flora. Few studies have investigated the effect of serum carotenoids on the development and pathogenesis of BV. This study thus aimed to explore the correlation between serum carotenoids and BV in American women. METHOD: The analysis included 1252 participants with BV from the National Health and Nutrition Examination Survey (NHANES) between 2001 and 2004. Multiple logistic regression was conducted to explore the correlation between BV and serum carotenoids, while smooth curve fitting was utilized to examine potential nonlinear correlations. Furthermore, stratified subgroup analyses and sensitivity analyses were conducted. ORs reflected the correlation between BV and serum carotenoids. RESULT: Results of multiple logistic regression indicated that total serum carotenoids and BV had an inverse correlation. In the fully adjusted model II, the quartile with the highest levels of α-carotene and ß-cryptoxanthin had a substantially lower incidence of BV. Smooth curve fitting revealed a significant negative linear correlation between serum carotenoids and the incidence of BV. The negative correlation between serum carotenoids and BV was relatively stable in stratified analyses. Moreover, in sensitivity analyses, the association between serum carotenoids and BV persisted, and ß-carotene became significantly negatively correlated with BV. CONCLUSION: This study found an inverse correlation between serum carotenoids and the prevalence of BV.


Subject(s)
Vaginosis, Bacterial , Humans , Female , United States/epidemiology , Nutrition Surveys , Vaginosis, Bacterial/epidemiology , Carotenoids , beta Carotene , Antioxidants
16.
Zootaxa ; 5397(2): 264-272, 2024 Jan 04.
Article in English | MEDLINE | ID: mdl-38221205

ABSTRACT

Only one species of Pendleburyella Chopard, 1969 (Gryllidae, Pentacentrinae) was previously known to occur in Borneo: Pendleburyella eirmosa Tan, Muhammad & Wahab, 2023 from Brunei Darussalam. Here, two additional new species of crickets from the genus Pendleburyella are described from the highlands of Sabah, Borneo: Pendleburyella eremita sp. nov. from Bukit Hampuan and Pendleburyella nimba sp. nov. from Mount Trus Madi. In total, six species of Pendleburyella are currently known, three from Borneo and three from Malay Peninsula. It is likely that many more species are awaiting discovery owing to its cryptic morphology and elusive nature.


Subject(s)
Cricket Sport , Gryllidae , Animals , Malaysia , Borneo
17.
Dalton Trans ; 53(5): 2143-2152, 2024 Jan 30.
Article in English | MEDLINE | ID: mdl-38189098

ABSTRACT

Mitophagy, a selective autophagic process, has emerged as a pathway involved in degrading dysfunctional mitochondria. Herein, new platinum(II)-based chemotherapeutics with mitophagy-targeting properties are proposed. Four novel binuclear anticancer Pt(II) complexes with 4'-substituted-2,2':6',2''-terpyridine derivatives (tpy1-tpy4), i.e., [Pt2(tpy1)(DMSO)2Cl4]·CH3OH (tpy1Pt), [Pt(tpy2)Cl][Pt(DMSO)Cl3]·CH3COCH3 (tpy2Pt), [Pt(tpy3)Cl][Pt(DMSO)Cl3] (tpy3Pt), and [Pt(tpy4)Cl]Cl·CH3OH (tpy4Pt), were designed and prepared. Moreover, their potential antitumor mechanism was studied. Tpy1Pt-tpy4Pt exhibited more selective cytotoxicity against cisplatin-resistant SK-OV-3/DDP (SKO3cisR) cancer cells compared with those against ovarian SK-OV-3 (SKO3) cancer cells and normal HL-7702 liver (H702) cells. This selective cytotoxicity of Tpy1Pt-tpy4Pt was better than that of its ligands (i.e., tpy1-tpy4), the clinical drug cisplatin, and cis-Pt(DMSO)2Cl2. The results of various experiments indicated that tpy1Pt and tpy2Pt kill SKO3cisR cancer cells via a mitophagy pathway, which involves the disruption of the mitophagy-related protein expression, dissipation of the mitochondrial membrane potential, elevation of the [Ca2+] and reactive oxygen species levels, promotion of mitochondrial DNA damage, and reduction in the adenosine triphosphate and mitochondrial respiratory chain levels. Furthermore, in vivo experiments indicated that the dinuclear anticancer Pt(II) coordination compound (tpy1Pt) has remarkable therapeutic efficiency (ca. 52.4%) and almost no toxicity. Therefore, the new 4'-substituted-2,2':6',2''-terpyridine Pt(II) coordination compound (tpy1Pt) is a potential candidate for next-generation mitophagy-targeting dinuclear Pt(II)-based anticancer drugs.


Subject(s)
Antineoplastic Agents , Cisplatin , Cisplatin/pharmacology , Platinum/pharmacology , Dimethyl Sulfoxide , Cell Line, Tumor , Organoplatinum Compounds/pharmacology , Antineoplastic Agents/pharmacology , Apoptosis
18.
Ultrasonics ; 138: 107234, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38171227

ABSTRACT

The development of alternative techniques to efficiently inactivate bacterial suspensions is crucial to prevent transmission of waterborne illness, particularly when commonly used techniques such as heating, filtration, chlorination, or ultraviolet treatment are not practical or feasible. We examine the effect of MHz-order acoustic wave irradiation in the form of surface acoustic waves (SAWs) on Gram-positive (Escherichia coli) and Gram-negative (Brevibacillus borstelensis and Staphylococcus aureus) bacteria suspended in water droplets. A significant increase in the relative bacterial load reduction of colony-forming units (up to 74%) can be achieved by either increasing (1) the excitation power, or, (2) the acoustic treatment duration, which we attributed to the effect of the acoustic radiation force exerted on the bacteria. Consequently, by increasing the maximum pressure amplitude via a hybrid modulation scheme involving a combination of amplitude and pulse-width modulation, we observe that the bacterial inactivation efficiency can be further increased by approximately 14%. By combining this scalable acoustic-based bacterial inactivation platform with plasma-activated water, a 100% reduction in E. coli is observed in less than 10 mins, therefore demonstrating the potential of the synergistic effects of MHz-order acoustic irradiation and plasma-activated water as an efficient strategy for water decontamination.


Subject(s)
Bacteria , Escherichia coli , Bacteria/radiation effects , Sound , Acoustics , Water
19.
Int J Biol Macromol ; 260(Pt 2): 129613, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38246440

ABSTRACT

The effects of pulsed electric field combined with ultrasound (PEF-US) on the recovery of polyphenols from litchi peels were investigated. In addition, the optimal purification parameters for polyphenol extracts and their biological activities were also explored in this study. Single-factor and orthogonal experiments were used to optimize the extraction conditions of polyphenols. After optimization, the total phenol content (TPC) of the sample extracted by PEF-US was 2.30 times higher than that of the sample extracted by traditional hot-water extraction. The mechanism of PEF-US enhancing polyphenol recovery was also revealed by morphological analysis of the powder surface. LX-7 was the best resin by comparing the purification effect of nine macroporous resins. The optimum conditions for purification of litchi peel polyphenols by LX-7 resin were also optimized through adsorption and desorption experiments. UHPLC-MS and HPLC results revealed that gentisic acid, catechin, procyanidin A2 and procyanidin B1 are four main substances in purified samples. The results of bioactivity experiments showed that the purified polyphenol samples had strong antioxidant and antibacterial activity. Overall, PEF-US is an efficient method for recovering polyphenols from litchi peels. Our study also provides a strategy for the comprehensive utilization of fruit processing waste.


Subject(s)
Litchi , Polyphenols , Fruit/chemistry , Plant Extracts , Antioxidants/pharmacology
20.
Virol J ; 21(1): 35, 2024 01 31.
Article in English | MEDLINE | ID: mdl-38297280

ABSTRACT

BACKGROUND: Progressive hepatitis B virus (HBV) infection can result in cirrhosis, hepatocellular cancer, and chronic hepatitis. While antiviral drugs that are now on the market are efficient in controlling HBV infection, finding a functional cure is still quite difficult. Identifying host factors involved in regulating the HBV life cycle will contribute to the development of new antiviral strategies. Zinc finger proteins have a significant function in HBV replication, according to earlier studies. Zinc finger protein 148 (ZNF148), a zinc finger transcription factor, regulates the expression of various genes by specifically binding to GC-rich sequences within promoter regions. The function of ZNF148 in HBV replication was investigated in this study. METHODS: HepG2-Na+/taurocholate cotransporting polypeptide (HepG2-NTCP) cells and Huh7 cells were used to evaluate the function of ZNF148 in vitro. Northern blotting and real-time PCR were used to quantify the amount of viral RNA. Southern blotting and real-time PCR were used to quantify the amount of viral DNA. Viral protein levels were elevated, according to the Western blot results. Dual-luciferase reporter assays were used to examine the transcriptional activity of viral promoters. ZNF148's impact on HBV in vivo was investigated using an established rcccDNA mouse model. RESULTS: ZNF148 overexpression significantly decreased the levels of HBV RNAs and HBV core DNA in HBV-infected HepG2-NTCP cells and Huh7 cells expressing prcccDNA. Silencing ZNF148 exhibited the opposite effects in both cell lines. Furthermore, ZNF148 inhibited the activity of HBV ENII/Cp and the transcriptional activity of cccDNA. Mechanistic studies revealed that ZNF148 attenuated retinoid X receptor alpha (RXRα) expression by binding to the RXRα promoter sequence. RXRα binding site mutation or RXRα overexpression abolished the suppressive effect of ZNF148 on HBV replication. The inhibitory effect of ZNF148 was also observed in the rcccDNA mouse model. CONCLUSIONS: ZNF148 inhibited HBV replication by downregulating RXRα transcription. Our findings reveal that ZNF148 may be a new target for anti-HBV strategies.


Subject(s)
Hepatitis B virus , Hepatitis B , Animals , Mice , Humans , Hepatitis B virus/physiology , Virus Replication , Hep G2 Cells , Transcription Factors/genetics , Transcription Factors/metabolism , DNA, Viral/genetics
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