Development of natural product-based targeted protein degraders as anticancer agents.

Targeted protein degradation (TPD) has emerged as a powerful approach for eliminating cancer-causing proteins through an "event-driven" pharmacological mode. Proteolysis-targeting chimeras (PROTACs), molecular glues (MGs), and hydrophobic tagging (HyTing) have evolved into three major classes of TPD technologies. Natural products (NPs) are a primary source of anticancer drugs and have played important roles in the development of TPD technology. NPs potentially expand the toolbox of TPD by providing a variety of E3 ligase ligands, protein of interest (POI) warheads, and hydrophobic tags (HyTs). As a promising direction in the TPD field, NP-based degraders have shown great potential for anticancer therapy. In this review, we summarize recent advances in the development of NP-based degraders (PROTACs, MGs and HyTing) with anticancer applications. Moreover, we put forward the challenges while presenting potential opportunities for the advancement of future targeted protein degraders derived from NPs.

Biomechanical analysis of the effect of Class II traction configurations and aligner overtreatment on molar distalization: a finite-element study.

OBJECTIVE: This study aimed to evaluate the biomechanical effects of aligner overtreatment on molar distalization using clear aligners. METHODS: Various models were created and integrated into finite-element software. Six distinct study models were devised for analysis. The first three models examined second molar distalization with different configurations of attachments, i.e. no attachment, horizontal or vertical attachment on the second molar. For the fourth and fifth models, Class II elastic traction, either implemented via a precision cut or button on canines, was applied. Lastly, aligner overtreatment with varying degrees of root distal tipping (0°, 2°, 4°, 6°, 8°, 10°, and 12°) for the second molar was designed in the last study model. RESULTS: Distalization of the second molar produced buccal tipping, distal tipping and intrusion of the second molar, and labial proclination and intrusion of the central incisor. These displacement tendencies were enhanced by adding attachments on the second molar, especially the vertical attachment. Class II elastic tractions enhanced molar distalization and diminish anchorage loss, with the precision-cut configuration being biomechanically superior to the button design. Aligner overtreatment produced bodily molar distalization and mitigated adverse biomechanical effects on anchorage teeth. LIMITATIONS: The study's limitations include the use of finite-element models, which may not fully represent real clinical scenarios, and the lack of consideration for individual patient variability. CONCLUSIONS: We suggest that Class II elastic traction via the precision-cut configuration and the design of vertical attachment on the second molar be applied for molar distalization. Appropriate aligner overtreatment helps achieve bodily molar distalization and minimizes adverse biomechanical effects on anchorage teeth.

Primary aldosteronism and lower-extremity arterial disease: a two-sample Mendelian randomization study.

BACKGROUND AND AIMS: Primary aldosteronism (PA) is an adrenal disorder of autonomous aldosterone secretion which promotes arterial injury. We aimed to explore whether PA is causally associated with lower-extremity arterial disease (LEAD). METHODS: We included 39,713 patients with diabetes and 419,312 participants without diabetes from UK Biobank. We derived a polygenic risk score (PRS) for PA based on previous genome-wide association studies (GWAS). Outcomes included LEAD and LEAD related gangrene or amputation. We conducted a two-sample Mendelian randomization analysis for PA and outcomes to explore their potential causal relationship. RESULTS: In whole population, individuals with a higher PA PRS had an increased risk of LEAD. Among patients with diabetes, compared to the subjects in the first tertile of PA PRS, subjects in the third tertile showed a 1.24-fold higher risk of LEAD (OR 1.24, 95% CI 1.03-1.49) and a 2.09-fold higher risk of gangrene (OR 2.09, 95% CI 1.27-3.44), and 1.72-fold higher risk of amputation (OR 1.72, 95% CI 1.10-2.67). Among subjects without diabetes, there was no significant association between PA PRS and LEAD, gangrene or amputation. Two-sample Mendelian randomization analysis indicated that genetically predictors of PA was significantly associated with higher risks of LEAD and gangrene (inverse variance weighted OR 1.20 [95% CI 1.08-1.34]) for LEAD, 1.48 [95% CI 1.28-1.70] for gangrene), with no evidence of significant heterogeneity or directional pleiotropy. CONCLUSIONS: Primary aldosteronism is genetically and causally associated with higher risks of LEAD and gangrene, especially among patients with diabetes. Targeting on the autonomous aldosterone secretion may prevent LEAD progression.

A comparison of maxillofacial growth in Chinese children with isolated cleft palate treated with two different palatoplasty techniques without relaxing incisions: a preliminary study.

OBJECTIVE: To assess the maxillofacial growth of patients with isolated cleft palate following the Sommerlad-Furlow modified technique and compare it with the effect of the Sommerlad technique. STUDY DESIGN: A Retrospective Cohort Study. METHODS: A total of 90 participants, 60 patients with non-syndromic isolated soft and hard cleft palate (ISHCP) underwent primary palatoplasty without relaxing incision (30 patients received the Sommerlad-Furlow modified (S-F) technique and 30 received Sommerlad (S) technique). While the other 30 were healthy noncleft participants with skeletal class I pattern (C group). All participants had lateral cephalometric radiographs at least 5 years old age. All the study variables were measured by using stable landmarks, including 11 linear and 9 angular variants. RESULTS: The means age at collection of cephalograms were 6.03 ± 0.80 (5-7 yrs) in the S group, 5.96 ± 0.76 (5-7 yrs) in the S-F group, and 5.91 ± 0.87 (5-7 yrs) in the C group. Regarding cranial base, the results showed that there were no statistically significant differences between the three groups in S-N and S-N-Ba. The S group had a significantly shortest S-Ba than the S-F & C groups (P = 0.01), but there was no statistically significant difference between S-F and C groups (P = 0.80). Regarding skeletal maxillary growth, the S group had significantly shorter Co-A, S- PM and significantly less SNA angle than the C group (P = < 0.01). While there was no significant difference between S-F & C groups (P = 0.42). The S group had significantly more MP-SN inclination than the C group (P = < 0.01). Regarding skeletal mandibular growth, there were no statistically significant differences in all linear and angular mandibular measurements between the three groups, except Co-Gn of the S group had a significantly shorter length than the C group (P = 0.05). Regarding intermaxillary relation, the S-F group had no significant differences in Co-Gn-Co-A and ANB as compared with the C group. The S group had significantly less ANB angle than S-F & C groups (P = 0.01 & P = < 0.01). In addition, there were no significant differences in all angular occlusal measurements between the three groups. CONCLUSION: As a preliminary report, Sommerlad-Furlow modified technique showed that maxillary positioning in the face tended to be better, and the intermaxillary relationship was more satisfactory than that in Sommerlad technique when compared them in healthy noncleft participants.

Distribution and drug sensitivity of pathogenic bacteria in diabetic foot ulcer patients with necrotizing fasciitis at a diabetic foot center in China.

BACKGROUND: Diabetic foot ulcer is one of the major complications for patients with diabetes, and has become an important cause of non-traumatic amputation. Necrotizing fasciitis is a life-threatening soft-tissue infection involving the fascia and subcutaneous tissue. When diabetic foot ulcers are complicated by necrotizing fasciitis (DNF), this increases the risk for amputation and mortality, making DNF treatment more complicated, and eventually leading to amputation and mortality. However, studies on pathogenic bacteria's distribution and drug sensitivity in DNF patients remain lacking. This study investigated the distribution and susceptibility of pathogenic bacteria in DNF patients, and provided empirical antibacterial guidance for the clinic. METHODS: In a single diabetic foot center, the results from microbial cultures and drug susceptibility tests of patients with DNF from October 2013 to December 2020 were collected and analyzed. RESULTS: A total of 101 DNF patients were included in this study, of whom 94 had positive culture test results. A total of 124 pathogens were cultured, including 76 Gram-positive bacterial strains, 42 Gram-negative bacterial strains, and six fungal strains. Polymicrobial infections accounted for 26.7% and monomicrobial infections accounted for 66.3%. Staphylococcus aureus was the most common bacterium isolated, followed by Enterococcus faecalis and Streptococcus agalactiae. Pseudomonas aeruginosa, Klebsiella pneumoniae, and Proteus mirabilis were the most common Gram-negative bacteria. Thirty-five strains of multi-drug resistant bacteria were isolated, representing 28.2% of the total isolates. Gram-positive bacteria were more sensitive to levofloxacin, moxifloxacin, vancomycin, teicoplanin, tigecycline, and linezolid, while Gram-negative bacteria were more sensitive to amikacin, piperacillin/tazobactam, cefoperazone/sulbactam, ceftazidime, cefepime, imipenem, and meropenem. CONCLUSIONS: Gram-positive bacteria were the main bacteria isolated from DNF patients. The bacterial composition, the proportion of multi-drug resistant bacteria among the pathogens, and the high risk for amputation should be fully considered in the initial empirical medication, and broad-spectrum antibacterials are recommended.

Molecular mechanism in trigeminal nerve and treatment methods related to orthodontic pain.

BACKGROUND: Orthodontic treatment is the main treatment approach for malocclusion. Orthodontic pain is an inevitable undesirable adverse reaction during orthodontic treatment. It is reported orthodontic pain has become one of the most common reason that patients withdraw from orthodontic treatment. Therefore, understanding the underlying mechanism and finding treatment of orthodontic pain are in urgent need. AIMS: This article aims to sort out the mechanisms and treatments of orthodontic pain, hoping to provide some ideas for future orthodontic pain relief. MATERIALS: Tooth movement will cause local inflammation. Certain inflammatory factors and cytokines stimulating the trigeminal nerve and further generating pain perception, as well as drugs and molecular targeted therapy blocking nerve conduction pathways, will be reviewed in this article. METHOD: We review and summaries current studies related to molecular mechanisms and treatment approaches in orthodontic pain control. RESULTS: Orthodontics pain related influencing factors and molecular mechanisms has been introduced. Commonly used clinical methods in orthodontic pain control has been evaluated. DISCUSSION: With the clarification of more molecular mechanisms, the direction of orthodontic pain treatment will shift to targeted drugs.

Panax Notoginseng Saponins Combined with Dual Antiplatelet Drugs Potentiates Anti-Thrombotic Effect with Alleviated Gastric Injury in A Carotid Artery Thrombosis Rat Model.

OBJECTIVE: To observe the combination effects of Panax notoginseng saponins (PNS)and dual antiplatelet drugs (DAPT), and to explore the mechanism via cyclooxygenase /prostaglandin pathway. METHODS: Right carotid artery thrombosis was induced in Wistar rats by infiltration with 70% FeCl3, and the animals were randomly divided into sham group, model group, DAPT group and PNS + DAPT group, intragastrically treated for 4 weeks. The cerebral pia mater microcirculation was observed in vivo after anesthetizing by anatomical microscope. The wet weight of carotid artery thrombosis was measured. Gastric mucosal injury was observed by hematoxylin and eosin staining. Platelet aggregation rate was detected with adenosine diphosphate -induced turbidimetry. Platelet CD62p expression was detected by flow cytometry. Concentrations of 6-Ketoprostaglandin F1 alpha, prostaglandin E2 in gastric mucosa and thromboxane B2, 6-Ketoprostaglandin F1 alpha, tissue plasminogen activator, plasminogen activator inhibitor, and fibrin fragment D in the plasma were measured by radioimmunoassay. RESULTS: PNS and DAPT increased the blood flow volume of cerebral pia mater and decreased erythrocyte aggregation and leukocyte adhesion of model rats. Compared to DAPT, PNS and DAPT further reduced the weight of carotid artery thrombosis with enhanced inhibition of platelet aggregation, increased tissue plasminogen activator levels and decreased fibrin fragment D levels. PNS and DAPT alleviated gastric injury induced by dual antiplatelet drugs and upregulated the expression of 6-Ketoprostaglandin F1 alpha in the gastric mucosa compared with DAPT. CONCLUSIONS: PNS combined with DAPT increased anti-thrombosis effects of DAPT and mitigated DAPT-related gastric injury. The underlying mechanisms may be associated with enhanced antiplatelet aggregation and activation of the fibrinolytic system and up-regulation of 6-Ketoprostaglandin F1 alpha expression in gastric mucosa.

Attention-Guided Image Captioning through Word Information.

Image captioning generates written descriptions of an image. In recent image captioning research, attention regions seldom cover all objects, and generated captions may lack the details of objects and may remain far from reality. In this paper, we propose a word guided attention (WGA) method for image captioning. First, WGA extracts word information using the embedded word and memory cell by applying transformation and multiplication. Then, WGA applies word information to the attention results and obtains the attended feature vectors via elementwise multiplication. Finally, we apply WGA with the words from different time steps to obtain previous word guided attention (PW) and current word attention (CW) in the decoder. Experiments on the MSCOCO dataset show that our proposed WGA can achieve competitive performance against state-of-the-art methods, with PW results of a 39.1 Bilingual Evaluation Understudy score (BLEU-4) and a 127.6 Consensus-Based Image Description Evaluation score (CIDEr-D); and CW results of a 39.1 BLEU-4 score and a 127.2 CIDER-D score on a Karpathy test split.

Adipose Lipolysis Regulates Cardiac Glucose Uptake and Function in Mice under Cold Stress.

The heart primarily uses fatty acids as energy substrates. Adipose lipolysis is a major source of fatty acids, particularly under stress conditions. In this study, we showed that mice with selective inactivation of the lipolytic coactivator comparative gene identification-58 (CGI-58) in adipose tissue (FAT-KO mice), relative to their littermate controls, had lower circulating FA levels in the fed and fasted states due to impaired adipose lipolysis. They preferentially utilized carbohydrates as energy fuels and were more insulin sensitive and glucose tolerant. Under cold stress, FAT-KO versus control mice had >10-fold increases in glucose uptake in the hearts but no increases in other tissues examined. Plasma concentrations of atrial natriuretic peptide and cardiac mRNAs for atrial and brain-type natriuretic peptides, two sensitive markers of cardiac remodeling, were also elevated. After one week of cold exposure, FAT-KO mice showed reduced cardiac expression of several mitochondrial oxidative phosphorylation proteins. After one month of cold exposure, hearts of these animals showed depressed functions, reduced SERCA2 protein, and increased proteins for MHC-ß, collagen I proteins, Glut1, Glut4 and phospho-AMPK. Thus, CGI-58-dependent adipose lipolysis critically regulates cardiac metabolism and function, especially during cold adaptation. The adipose-heart axis may be targeted for the management of cardiac dysfunction.

Radiographic evaluation of immature traumatized incisors following different endodontic treatments.

BACKGROUND/AIMS: Indirect pulp capping, pulpotomy, and apexification are three common endodontic treatments for immature traumatized incisors. They all affect tooth root development to some extent. The aim of this retrospective study was to compare the influence of these treatments on root development of immature permanent incisors following dental trauma. MATERIALS AND METHODS: Twenty-one indirect pulp capping, 48 pulpotomy, and 58 apexification cases with a mean age of 8.4 ± 1.0 years and median follow up of 12 months were included. NIH ImageJ with TurboReg plug-in was used to correct angular differences between the pre-operative and recall periapical radiographs, and to calculate variations of root length, dentin wall thickness, and apical closure. Kruskal-Wallis ANOVA followed by pairwise comparisons was applied to compare the radiographic variations. The type of apical closure was assessed qualitatively and analyzed using Fisher's exact test. RESULTS: The apexification group had a lower trend toward apical closure than the other two groups (P < .05). It also showed thinner dentin wall thickness compared with the pulpotomy group (P = .001). There was no significant difference between pulpotomy and indirect pulp capping in the trend to apical closure (P > .05) or dentin wall thickness (P = .775). There was no significant difference in the variation of root length among the three groups (P = .06). There was a moderate correlation between the treatment and the type of apical closure (Cramer's V Coefficient = .375). Pulpotomy tended to form a normal apical constriction rather than a calcific barrier while apexification showed the opposite inclination. Indirect pulp capping had no specific inclination toward any type of apical closure. CONCLUSIONS: Apexification resulted in an abnormal root development mostly by affecting the dentin wall thickness and apical closure. Pulpotomy was beneficial for normal root development of immature traumatized teeth.

A plant RNA virus activates selective autophagy in a UPR-dependent manner to promote virus infection.

Autophagy is an evolutionarily conserved pathway in eukaryotes that delivers unwanted cytoplasmic materials to the lysosome/vacuole for degradation/recycling. Stimulated autophagy emerges as an integral part of plant immunity against intracellular pathogens. In this study, we used turnip mosaic virus (TuMV) as a model to investigate the involvement of autophagy in plant RNA virus infection. The small integral membrane protein 6K2 of TuMV, known as a marker of the virus replication site and an elicitor of the unfolded protein response (UPR), upregulates the selective autophagy receptor gene NBR1 in a UPR-dependent manner. NBR1 interacts with TuMV NIb, the RNA-dependent RNA polymerase of the virus replication complex (VRC), and the autophagy cargo receptor/adaptor protein ATG8f. The NIb/NBR1/ATG8f interaction complexes colocalise with the 6K2-stained VRC. Overexpression of NBR1 or ATG8f enhances TuMV replication, and deficiency of NBR1 or ATG8f inhibits virus infection. In addition, ATG8f interacts with the tonoplast-specific protein TIP1 and the NBR1/ATG8f-containing VRC is enclosed by the TIP1-labelled tonoplast. In TuMV-infected cells, numerous membrane-bound viral particles are evident in the vacuole. Altogether these results suggest that TuMV activates and manipulates UPR-dependent NBR1-ATG8f autophagy to target the VRC to the tonoplast to promote viral replication and virion accumulation.

An enantioselective assembly of naphthopyran via NHC-catalyzed [3 + 3] annulation of bromoenal with ß-tetralone.

An asymmetric assembly of naphthopyran was realized via the N-heterocyclic carbene (NHC)-catalyzed formal [3 + 3] annulation of bromoenal and ß-tetralone. The key advantages of this protocol include ready availability of starting materials, mild reaction conditions, good yields and excellent enantioselectivities.

Antibacterial activity of indolyl-quinolinium derivatives and study their mode of action.

Filamenting temperature-sensitive mutant Z (FtsZ) is recognized as a promising target for new antibiotics development because of its high conservatism and pivotal role in the bacteria cell division. The aromatic heterocyclic scaffold of indole is known showing merit medical functions in antiviral and antimicrobial. In the present study, a series of 1-methylquinolinium derivatives, which were integrated with an indole fragment at its 2-position and a variety of amino groups (cyclic or linear, mono- or di-amine) at the 4-position were synthesized and their antibacterial activities were evaluated. The results of antibacterial study show that the representative compounds can effectively inhibit the growth of testing strains including MRSA and VRE, with MIC values of 1-4 µg/mL by bactericidal mode. The mode of action assays revealed that c2 can effectively disrupt the rate of GTP hydrolysis and dynamic polymerization of FtsZ, and thus inhibits bacterial cell division and then causes bacterial cell death. In addition, the result of resistance generation experiment reveals that c2 is not likely to induce resistance in S. aureus.

Orthodontic Practitioners' Knowledge and Education Demand on Clear Aligner Therapy.

OBJECTIVES: Clear aligner therapy (CAT) has been gaining popularity amongst the orthodontic community. No systematic course on CAT has been reported to date. The objectives of this study were to determine practitioners' knowledge and to offer insights for future tailored courses on CAT. METHODS: An online questionnaire was distributed. The questionnaire comprised personal background information, predictability of tooth movement through CAT, and CAT knowledge that practitioners demanded to learn. Four senior expert orthodontists' answers to the predictability of tooth movement through CAT were averaged to be a standard reference. Descriptive statistics, 1-way analysis of variance (ANOVA), principal component analysis, Student t test, and multivariate logistics regression analysis were performed with significance set at P < .05. RESULTS: In total, 190 practitioners participated in this study. As compared to the standard reference, participants overestimated the predictability of difficult-to-be-achived tooth movements (eg, molar mesialisation; P < .0001). Strategy of managing troubleshooting cases and extraction cases ranked the highest CAT knowledge that participants requested to learn. Practice type, number of completed CAT cases, number of undergoing CAT cases, years of practice, education background, and time of using CAT were the influencing factors of the questions regarding the predictability of tooth movement through CAT and CAT knowledge that were demanded to be learned. CONCLUSIONS: The predictability of difficult-to-be-achieved tooth movement through CAT is often overestimated by practitioners with limited clinical experience. Tailored education on CAT, especially managing troubleshooting cases and extraction cases, should be designed for all practitioners.

The role of competing endogenous RNA network in the development of hepatocellular carcinoma: potential therapeutic targets.

The current situation of hepatocellular carcinoma (HCC) management is challenging due to its high incidence, mortality, recurrence and metastasis. Recent advances in gene genetic and expression regulation have unveiled the significant role of non-coding RNA (ncRNA) in various cancers. This led to the formulation of the competing endogenous RNA (ceRNA) hypothesis, which posits that both coding RNA and ncRNA, containing miRNA response elements (MRE), can share the same miRNA sequence. This results in a competitive network between ncRNAs, such as lncRNA and mRNA, allowing them to regulate each other. Extensive research has highlighted the crucial role of the ceRNA network in HCC development, impacting various cellular processes including proliferation, metastasis, cell death, angiogenesis, tumor microenvironment, organismal immunity, and chemotherapy resistance. Additionally, the ceRNA network, mediated by lncRNA or circRNA, offers potential in early diagnosis and prevention of HCC. Consequently, ceRNAs are emerging as therapeutic targets for HCC. The complexity of these gene networks aligns with the multi-target approach of traditional Chinese medicine (TCM), presenting a novel perspective for TCM in combating HCC. Research is beginning to show that TCM compounds and prescriptions can affect HCC progression through the ceRNA network, inhibiting proliferation and metastasis, and inducing apoptosis. Currently, the lncRNAs TUG1, NEAT1, and CCAT1, along with their associated ceRNA networks, are among the most promising ncRNAs for HCC research. However, this field is still in its infancy, necessitating advanced technology and extensive basic research to fully understand the ceRNA network mechanisms of TCM in HCC treatment.

Improving the solubility and interfacial absorption of hempseed protein via a novel high pressure homogenization-assisted pH-shift strategy.

A pH shift treatment aided by high pressure homogenization (HPH) with various pressures (0-120 MPa) was employed to structurally modify hempseed protein isolate (HPI). Compared with individual pH shift or HPH treatment, HPH-assisted pH shift improved the structural flexibility of HPI, as revealed by the increased random coil in protein secondary structure. With the incorporation of HPH into pH shift, the intrinsic fluorescence intensity was remarkably attenuated and redshifted, whereas the surface hydrophobicity was pronouncedly boosted, indicating the extensive unfolding of protein structure. Moreover, the cotreated HPI exhibited a smaller and more homogenous particle size, notably at a higher pressure. Consequently, the solubility was drastically raised by the cooperated treatments, to the maximum value (62.8 %) at 120 MPa. These physicochemical changes in the cotreated HPI facilitated a consolidated interfacial activity. Moreover, the cooperated treatment, especially highly pressured (120 MPa), facilitated the penetration and rearrangement of proteins at the oil-water interface.

Erratum: Author correction to 'Co-delivery of nigericin and decitabine using hexahistidine-metal nanocarriers for pyroptosis-induced immunotherapeutics' [Acta Pharm Sin B 12 (2022) 4458-4471].

[This corrects the article DOI: 10.1016/j.apsb.2022.11.002.].

Metabolic reprogramming in hepatocellular carcinoma: a bibliometric and visualized study from 2011 to 2023.

Background and aims: Metabolic reprogramming has been found to be a typical feature of tumors. Hepatocellular carcinoma (HCC), a cancer with high morbidity and mortality, has been extensively studied for its metabolic reprogramming-related mechanisms. Our study aims to identify the hotspots and frontiers of metabolic reprogramming research in HCC and to provide guidance for future scientific research and decision-making in HCC metabolism. Methods: Relevant studies on the metabolic reprogramming of HCC were derived from the Web of Science Core Collection (WoSCC) database up until November 2023. The bibliometrix tools in R were used for scientometric analysis and visualization. Results: From 2011 to 2023, a total of 575 publications were obtained from WoSCC that met the established criteria. These publications involved 3,904 researchers and 948 organizations in 37 countries, with an average annual growth rate of 39.11% in research. These studies were published in 233 journals, with Cancers (n = 29) ranking first, followed by Frontiers in Oncology (n = 20) and International Journal of Molecular Sciences (n = 19). The top ten journals accounted for 26% of the 575 studies. The most prolific authors were Wang J (n = 14), Li Y (n = 12), and Liu J (n = 12). The country with the most publications is China, followed by the United States, Italy, and France. Fudan University had the largest percentage of research results with 15.48% (n = 89). Ally A's paper in Cell has the most citations. A total of 1,204 keywords were analyzed, with the trend themes such as "glycolysis," "tumor microenvironment," "Warburg effect," "mitochondria," "hypoxia ," etc. Co-occurrence network and cluster analysis revealed the relationships between keywords, authors, publications, and journals. Moreover, the close collaboration between countries in this field was elucidated. Conclusion: This bibliometric and visual analysis delves into studies related to metabolic reprogramming in HCC between 2012 and 2023, elucidating the characteristics of research in this field, which has gradually moved away from single glycolipid metabolism studies to the integration of overall metabolism in the body, pointing out the trend of research topics, and the dynamics of the interaction between the tumor microenvironment and metabolic reprogramming will be the future direction of research, which provides blueprints and inspirations for HCC prevention and treatment programs to the researchers in this field.Systematic Review Registration: [https://www.bibliometrix.org].

GAPDH suppresses adenovirus-induced oxidative stress and enables a superfast production of recombinant adenovirus.

Recombinant adenovirus (rAdV) is a commonly used vector system for gene transfer. Efficient initial packaging and subsequent production of rAdV remains time-consuming and labor-intensive, possibly attributable to rAdV infection-associated oxidative stress and reactive oxygen species (ROS) production. Here, we show that exogenous GAPDH expression mitigates adenovirus-induced ROS-associated apoptosis in HEK293 cells, and expedites adenovirus production. By stably overexpressing GAPDH in HEK293 (293G) and 293pTP (293GP) cells, respectively, we demonstrated that rAdV-induced ROS production and cell apoptosis were significantly suppressed in 293G and 293GP cells. Transfection of 293G cells with adenoviral plasmid pAd-G2Luc yielded much higher titers of Ad-G2Luc at day 7 than that in HEK293 cells. Similarly, Ad-G2Luc was amplified more efficiently in 293G than in HEK293 cells. We further showed that transfection of 293GP cells with pAd-G2Luc produced much higher titers of Ad-G2Luc at day 5 than that of 293pTP cells. 293GP cells amplified the Ad-G2Luc much more efficiently than 293pTP cells, indicating that exogenous GAPDH can further augment pTP-enhanced adenovirus production. These results demonstrate that exogenous GAPDH can effectively suppress adenovirus-induced ROS and thus accelerate adenovirus production. Therefore, the engineered 293GP cells represent a superfast rAdV production system for adenovirus-based gene transfer and gene therapy.

The effect of antibiotics on the periodontal treatment of diabetic patients with periodontitis: A systematic review and meta-analysis.

Background: The aim of this meta-analysis was to compare the effects of periodontal treatment with or without adjunctive antibiotic on periodontal status and blood glucose level in diabetic patients with periodontitis. Methods: A search using electronic database (MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials) and a manual search were performed up to July 2022. Eligible 13 RCTs were included according to inclusion and exclusion criteria. Reviewers independently performed data screening, data selection, data extraction, and risk of bias. Quality assessment was performed according to the Cochrane Handbook for Systematic Reviews of Interventions. Weighted mean differences and 95% confidence intervals (CIs) for continuous outcomes were calculated using random or fixed-effects models. This review is registered in the PROSPERO database (CRD42022347803). Results: Of the 13 included articles, eight were on the use of systemic antibiotics and five on topical antibiotics. The results showed statistically significant improvement in periodontal status (probing depth, clinical attachment loss and bleeding on probing) at 6 months with systematic antibiotics use (PD-6M p = 0.04, BOP-6M p < 0.0001, CAL-6M p = 0.002). The improvement in PD with topical antibiotics was statistically significant at 1 month (p = 0.0006). However, there was no statistically significant improvement in periodontal status at 3 months with adjuvant systemic antibiotics. Conclusion: Antibiotics can improve the periodontal condition of diabetic patients with periodontitis to a certain extent. In clinical practice, it is necessary to comprehensively consider the balance of benefits and risks before deciding whether to use antibiotics. Systematic Review Registration: Identifier CRD42022347803, https://www.crd.york.ac.uk/PROSPERO/.