[Diagnostic values of anti-salivary gland protein-1 antibody combined with anti-parotid secretory protein antibody for Sjögren's syndrome].

OBJECTIVE: To assess the diagnostic value of anti-salivary gland protein-1 (SP1) antibody combined with anti-parotid secretory protein (PSP) antibody for Sjögren's syndrome (SS). METHODS: A total of 60 patients with primary SS (pSS) who were treated in the outpatient and inpatient department of Department of Rheumatology and Immunology of the Second Hospital of Hebei Medical University from January 2020 to December 2022 were collected. Thirty patients with other autoimmune diseases accompanied by dry mouth and/or dry eyes were collected as disease control group. Thirty healthy subjects from the physical examination center were collected for healthy control group, serum samples were obtained from all of them. Their general features and clinical information including clinical manifestations, laboratory examinations and other examinations were recorded. The 2016 American College of Rheumatology (ACR)/European League against Rheumatism (EULAR) classification criteria were adopted as the diagnostic standard of pSS. Immunoglobulin G (IgG) subtype of anti-SP1 antibody and anti-PSP antibody were detected by chemiluminescence immunoassay. The receiver operating characteristic (ROC) curve was used to evaluate the accuracy of anti-SP1 antibody and anti-PSP antibody in diagnosing pSS.The cli-nical characteristics of anti-SP1 antibody and anti-PSP antibody positive patients and negative patients in pSS group were further compared. Independent samples t test, Mann-Whitney U test, variance analysis, Kruskal-Wallis test, Chi-square test or Fisher's exact test and Spearman correlation analysis were used for statistical analysis. RESULTS: There was no significant difference in age (F=1.406, P=0.495) and gender (χ2=2.105, P=0.349) among pSS group, disease control group and healthy control group. The expression levels of anti-SP1 antibody (H=16.73, P < 0.001) and anti-PSP antibody (H=26.09, P < 0.001) were statistically different among the three groups. An intergroup comparison of anti-SP1 antibody expression levels showed that there was a statistically significant difference between pSS and healthy control group (P < 0.001), but no statistically significant difference between the other groups. Comparison of anti-PSP antibody expression levels between the groups showed that there were statistically significant differences between pSS and healthy control group (P < 0.001), and between disease control group and healthy control group (P=0.009), while no statistically significant differences between the other groups. The positive rate of anti-SP1 antibody in pSS group was significantly higher than that in disease control group and healthy control group (58.33% vs. 40.00% vs. 13.33%, P < 0.001). The positive rate of anti-PSP antibody in pSS group was significantly higher than that in disease control group and healthy control group (75.00% vs. 56.17% vs. 16.67%, P < 0.001). The area under the curve for anti-SP1 antibody was 0.688 (P < 0.001). The sensitivity and specificity of anti-SP1 antibody were 58.33% (35/60) and 70.00% (42/60) respectively, the positive predictive value was 66.04% (35/53) and the negative predictive value was 54.55% (42/77) of anti-SP1 antibody.The area under the curve of anti-PSP antibody was 0.720 (P < 0.001), with a sensitivity was 75.00% (45/60), and specificity was 63.33% (38/60).The positive predictive value and negative predictive value of anti-PSP antibody were 67.16% (45/67) and 71.70% (38/53) respectively. All the 13 pSS patients were negative for anti-Sjögren's syndrome A (SSA, including SSA52 and SSA60) antibody and anti- Sjögren's syndrome B (SSB) antibody. Among them, 11 patients were positive for both anti-SP1 antibody and anti-PSP antibody, 1 patient was positive for anti-SP1 antibody and 1 patient was positive for anti-PSP antibody. The clinical features of anti-SP1 antibody and anti-PSP antibody positive and negative groups were compared in pSS patients. The duration of disease in anti-SP1 antibody positive group was shorter (Z=-2.277, P=0.023) when compared with the negative patients. The patients with positive anti-PSP antibody were younger than those in the negative group (t=2.598, P < 0.05), the positive rate of rheumatoid factor (P=0.002) and the serum level of IgG (t=3.806, P=0.003) in anti-PSP antibody positive group were higher than in the negative group. Analysis of the correlation between anti-SP1 antibody and anti-PSP antibody in the pSS patients showed that there was significant correlation between them (r=0.801, P < 0.001). CONCLUSION: Both anti-SP1 antibody and anti-PSP antibody are valuable in the diagnosis of SS, and anti-SP1 antibody is helpful for the early diagnosis of pSS. The combined detection of anti-SP1 antibody and anti-PSP antibody is helpful for the early diagnosis of pSS patients with negative anti-SSA antibody and anti-SSB antibody.

Salp14 epitope-based mRNA vaccination induces early recognition of a tick bite.

Repeated exposure of animals to Ixodes scapularis ticks can result in acquired tick resistance (ATR). The first manifestation of ATR is erythema at the tick bite site, however, the specific peptide targets and mechanisms associated with this early aspect of ATR are not understood. In this study, we immunized guinea pigs with a lipid nanoparticle containing the mRNA encoding 25 amino acids in the carboxyl terminus of Salp14 (Salp14-C mRNA-LNP), an I. scapularis salivary protein. The animals produced high titers of IgG directed at the carboxyl terminus of Salp14. Guinea pigs immunized with Salp14-C mRNA-LNP and then exposed to I. scapularis, developed erythema at the tick bite site. Transcriptomics of the skin of guinea pigs at the I. scapularis bite sites elucidated selected pathways, including histamine activation, that are associated with the development of erythema. The study demonstrates that an mRNA vaccine encoding a small peptide can induce the initial phase of ATR in guinea pigs.

Comparative proteomic analysis of saliva from chewing tobacco users and oral cancer patients reveals shared biomarkers: A case control observational study.

OBJECTIVE: The aim of this study was to compare the salivary proteomic profile of smokeless tobacco users with that of non-users and oral cancer patients using Liquid Chromatography-Mass Spectrometry/ Mass Spectrometry (LC-MS/MS). METHODS: Saliva samples from 65 participants were collected in three groups: control (25 participants), smokeless tobacco users (25 participants), and oral cancer (15 participants). RESULTS: The analysis revealed 343 protein groups with significantly altered abundance in the saliva samples (P < 0.05). Among these, 43 out of 51 dysregulated proteins in the smokeless tobacco group were also dysregulated in the oral cancer group. Notably, Apolipoprotein A1 (ApoA1) and Pon1 were found to be significantly increased in both smokeless tobacco users and oral cancer patients (p < 0.05). Furthermore, six out of the 20 most significantly altered proteins were mitochondrial proteins, and all of these were decreased relative to controls in both smokeless tobacco users and cancer samples. CONCLUSION: The proteomic profile of users of chewing (smokeless) tobacco (SLT) shows substantial overlap in the altered pathways and dysregulated proteins with those altered in oral cancer samples, suggesting that SLT use induces a shift toward an oncogenic state. Specifically indicated pathways included blood microparticles, platelet α-granules and protease inhibitors as well as indicators of oxidative stress and exogenous compound processing. What differentiates oral cancer samples from SLT users is enrichment of alterations related to cytoskeletal organisation and tissue remodelling. CLINICAL SIGNIFICANCE: The findings emphasize the importance of salivary proteomic profiles because changes in certain proteins may be indicators for early oral cancer identification and risk assessment in smokeless tobacco users.

Salivary proteomic signatures in severe dental fluorosis.

The relationship between dental fluorosis and alterations in the salivary proteome remains inadequately elucidated. This study aimed to investigate the salivary proteome and fluoride concentrations in urine and drinking water among Thai individuals afflicted with severe dental fluorosis. Thirty-seven Thai schoolchildren, aged 6-16, were stratified based on Thylstrup and Fejerskov fluorosis index scores: 10 with scores ranging from 5 to 9 (SF) and 27 with a score of 0 (NF). Urinary and water fluoride levels were determined using an ion-selective fluoride electrode. Salivary proteomic profiling was conducted via LC-MS/MS, followed by comprehensive bioinformatic analysis. Results revealed significantly elevated urinary fluoride levels in the SF group (p = 0.007), whereas water fluoride levels did not significantly differ between the two cohorts. Both groups exhibited 104 detectable salivary proteins. The NF group demonstrated notable upregulation of LENG9, whereas the SF group displayed upregulation of LDHA, UBA1, S100A9, H4C3, and LCP1, all associated with the CFTR ion channel. Moreover, the NF group uniquely expressed 36 proteins, and Gene Ontology and pathway analyses suggested a link with various aspects of immune defense. In summary, the study hypothesized that the CFTR ion channel might play a predominant role in severe fluorosis and highlighted the depletion of immune-related salivary proteins, suggesting compromised immune defense in severe fluorosis. The utility of urinary fluoride might be a reliable indicator for assessing excessive fluoride exposure.

The human CD47 checkpoint is targeted by an immunosuppressive Aedes aegypti salivary factor to enhance arboviral skin infectivity.

The Aedes aegypti mosquito is a vector of many infectious agents, including flaviviruses such as Zika virus. Components of mosquito saliva have pleomorphic effects on the vertebrate host to enhance blood feeding, and these changes also create a favorable niche for pathogen replication and dissemination. Here, we demonstrate that human CD47, which is known to be involved in various immune processes, interacts with a 34-kilodalton mosquito salivary protein named Nest1. Nest1 is up-regulated in blood-fed female A. aegypti and facilitates Zika virus dissemination in human skin explants. Nest1 has a stronger affinity for CD47 than its natural ligand, signal regulatory protein α, competing for binding at the same interface. The interaction between Nest1 with CD47 suppresses phagocytosis by human macrophages and inhibits proinflammatory responses by white blood cells, thereby suppressing antiviral responses in the skin. This interaction elucidates how an arthropod protein alters the human response to promote arbovirus infectivity.

Opiorphin: an endogenous human peptide with intriguing application in diverse range of pathologies.

Mammalian zinc ectopeptidases have significant functions in deactivating neurological and hormonal peptide signals on the cell surface. The identification of Opiorphin, a physiological inhibitor of zinc ectopeptidases that inactivate enkephalin, has revealed its strong analgesic effects in both chemical and mechanical pain models. Opiorphin achieves this by increasing the transmission of endogenous opioids, which are dependent on the body's own opioid system. The function of opiorphin is closely linked to the rat sialorphin peptide, which inhibits pain perception by enhancing the activity of naturally occurring enkephalinergic pathways that depend on µ- and δ-opioid receptors. Opiorphin is highly intriguing in terms of its physiological implications within the endogenous opioidergic pathways, particularly in its ability to regulate mood-related states and pain perception. Opiorphin can induce antidepressant-like effects by influencing the levels of naturally occurring enkephalin, which are released in response to specific physical and/or psychological stimuli. This effect is achieved through the modulation of delta-opioid receptor-dependent pathways. Furthermore, research has demonstrated that opiorphin's impact on the cardiovascular system is facilitated by the renin-angiotensin system (RAS), sympathetic ganglia, and adrenal medulla, rather than the opioid system. Hence, opiorphin shows great potential as a solitary candidate for the treatment of several illnesses such as neurodegeneration, pain, and mood disorders.

Caffeine weakens the astringency of epigallocatechin gallate by inhibiting its interaction with salivary proteins.

The astringency of green tea is an integrated result of the synergic and antagonistic effects of individual tea components, whose mechanism is highly complex and not completely understood. Herein, we used an epigallocatechin gallate (EGCG)/caffeine (CAF)/saliva model to simulate the oral conditions during tea drinking. The effect of CAF on the interaction between EGCG and salivary proteins was first investigated using molecular docking and isothermal titration calorimetry (ITC). Then, the rheological properties and the micro-network structure of saliva were studied to relate the molecular interactions and perceived astringency. The results revealed that CAF partially occupied the binding sites of EGCG to salivary proteins, inhibiting their interaction and causing changes in the elastic network structure of the salivary film, thereby reducing astringency.

Plant viruses exploit insect salivary GAPDH to modulate plant defenses.

Salivary proteins of insect herbivores can suppress plant defenses, but the roles of many remain elusive. One such protein is glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from the saliva of the Recilia dorsalis (RdGAPDH) leafhopper, which is known to transmit rice gall dwarf virus (RGDV). Here we show that RdGAPDH was loaded into exosomes and released from salivary glands into the rice phloem through an exosomal pathway as R. dorsalis fed. In infected salivary glands of R. dorsalis, the virus upregulated the accumulation and subsequent release of exosomal RdGAPDH into the phloem. Once released, RdGAPDH consumed H2O2 in rice plants owing to its -SH groups reacting with H2O2. This reduction in H2O2 of rice plant facilitated R. dorsalis feeding and consequently promoted RGDV transmission. However, overoxidation of RdGAPDH could cause potential irreversible cytotoxicity to rice plants. In response, rice launched emergency defense by utilizing glutathione to S-glutathionylate the oxidization products of RdGAPDH. This process counteracts the potential cellular damage from RdGAPDH overoxidation, helping plant to maintain a normal phenotype. Additionally, salivary GAPDHs from other hemipterans vectors similarly suppressed H2O2 burst in plants. We propose a strategy by which plant viruses exploit insect salivary proteins to modulate plant defenses, thus enabling sustainable insect feeding and facilitating viral transmission.

Tick salivary proteome and lipidome with low glycan content correlate with allergic type reactions in the zebrafish model.

Ticks, as hematophagous ectoparasites, can manipulate host immune and metabolic processes, causing tick-borne allergies such as α-Gal syndrome (AGS). Glycolipids with bound galactose-alpha-1-3-galactose (α-Gal) are potential allergenic molecules associated with AGS. Nevertheless, proteins and lipids lacking α-Gal modifications may contribute to tick salivary allergies and be linked to AGS. In this study, we characterized the effect of deglycosylated tick salivary proteins without lipids on treated zebrafish fed with dog food formulated with mammalian (beef, lamb, pork) meat by quantitative proteomics analysis of intestinal samples. The characterization and functional annotations of tick salivary lipids with low representation of glycolipids was conducted using a lipidomics approach. Results showed a significant effect of treatment with saliva and saliva deglycosylated protein fraction on zebrafish abnormal or no feeding (p < 0.005). Treatment with this fraction affected multiple metabolic pathways, defense responses to pathogens and protein metabolism, which correlated with abnormal or no feeding. Lipidomics analysis identified 23 lipid classes with low representation of glycolipids (0.70% of identified lipids). The lipid class with highest representation was phosphatidylcholine (PC; 26.66%) and for glycolipids it corresponded to diacylglycerol (DG; 0.48%). Qualitative analysis of PC antibodies revealed that individuals bitten by ticks were more likely to produce PC-IgG antibodies (p < 0.001). DG levels were significantly higher in tick salivary glands (p < 0.05) compared with tick saliva and salivary fractions. The α-Gal content was higher in tick saliva than in deglycosylated saliva and lipid fractions. These results support a possible role for tick salivary proteins and lipids without α-Gal modifications in AGS.

Identification of potential differences in salivary proteomic profiles between estrus and diestrus stage of estrous cycle in dairy cows.

In the present study, a comparative global high-throughput proteomic analysis strategy was used to identify proteomic differences between estrus and diestrus stage of estrous cycle in dairy cows. Saliva was collected from cows during estrus and diestrus, and subjected to LC-MS/MS-based proteomic analysis. A total of 2842 proteins were detected in the saliva of cows, out of which, 2437 and 1428 non-redundant proteins were identified in estrous and diestrous saliva, respectively. Further, it was found that 1414 and 405 salivary proteins were specific to estrus and diestrus, respectively while 1023 proteins were common to both groups. Among the significantly dysregulated proteins, the expression of 56 proteins was down-regulated (abundance ratio <0.5) while 40 proteins were up-regulated (abundance ratio > 2) in estrous compared to diestrous saliva. The proteins, such as HSD17B12, INHBA, HSP70, ENO1, SRD5A1, MOS, AMH, ECE2, PDGFA, OPRK1, SYN1, CCNC, PLIN5, CETN1, AKR1C4, NMNAT1, CYP2E1, and CYP19A1 were detected only in the saliva samples derived from estrous cows. Considerable number of proteins detected in the saliva of estrous cows were found to be involved in metabolic pathway, PI3K-Akt signaling pathway, toll-like receptor signaling pathway, steroid biosynthesis pathway, insulin signaling pathway, calcium signaling pathway, estrogen signaling pathway, oxytocin signaling pathway, TGF-ß signaling pathway and oocyte meiosis. On the other hand, proteins detected in saliva of diestrous cows were involved mainly in metabolic pathway. Collectively, these data provide preliminary evidence of a potential difference in salivary proteins at different stages of estrous cycle in dairy cows.

Utility of plasma anti-gSG6-P1 IgG levels in determining changes in Anopheles gambiae bite rates in a rural area of Cameroon.

The applicability of the specific human IgG antibody response to Anopheles gambiae salivary Gland Protein-6 peptide 1 (gSG6-P1 salivary peptide) as a biomarker able to distinguish the level of exposure to mosquito bites according to seasonal variations has not yet been evaluated in Central African regions. The study aimed to provide the first reliable data on the IgG anti-gSG6-P1 response in rural area in Cameroon according to the dry- and rainy-season. Between May and December 2020, dry blood samples were collected from people living in the Bankeng village in the forest area of the Centre region of Cameroon. Malaria infection was determined by thick-blood smear microscopy and multiplex PCR. The level of IgG anti-gSG6-P1 response, was assessed by enzyme-linked immunosorbent assay. Anopheles density and aggressiveness were assessed using human landing catches. The prevalence of malaria infection remains significantly higher in the rainy season than in the dry season (77.57% vs 61.44%; p = 0.0001). The specific anti-gSG6-P1 IgG response could be detected in individuals exposed to few mosquito bites and showed inter-individual heterogeneity even when living in the same exposure area. In both seasons, the level of anti-gSG6-P1 IgG response was not significantly different between Plasmodium infected and non-infected individuals. Mosquito bites were more aggressive in the rainy season compared to the dry season (human biting rate-HBR of 15.05 b/p/n vs 1.5 b/p/n) where mosquito density was very low. Infected mosquitoes were found only during the rainy season (sporozoite rate = 10.63% and entomological inoculation rate-EIR = 1.42 ib/p/n). The level of IgG anti-gSG6-P1 response was significantly higher in the rainy season and correlated with HBR (p ˂ 0.0001). This study highlights the high heterogeneity of individual's exposure to the Anopheles gambiae s.l vector bites depending on the transmission season in the same area. These findings reinforce the usefulness of the anti-gSG6-P1 IgG response as an accurate immunological biomarker for detecting individual exposure to Anopheles gambiae s.l. bites during the low risk period of malaria transmission in rural areas and for the differentiating the level of exposure to mosquitoes.

Effect of Silencing subolesin and enolase impairs gene expression, engorgement and reproduction in Haemaphysalis longicornis (Acari: Ixodidae) ticks.

IMPORTANCE: Haemaphysalis longicornis is an obligate blood-sucking ectoparasite that has gained attention due its role of transmitting medically and veterinary significant pathogens and it is the most common tick species in Republic of Korea. The preferred strategy for controlling ticks is a multi-antigenic vaccination. Testing the efficiency of a combination antigen is a promising method for creating a tick vaccine. OBJECTIVE: The aim of the current research was to analyze the role of subolesin and enolase in feeding and reproduction of H. longicornis by gene silencing. METHODS: In this study, we used RNA interference to silence salivary enolase and subolesin in H. longicornis. Unfed female ticks injected with double-stranded RNA targeting subolesin and enolase were attached and fed normally on the rabbit's ear. Real-time polymerase chain reaction was used to confirm the extent of knockdown. RESULTS: Ticks in the subolesin or enolase dsRNA groups showed knockdown rates of 80% and 60% respectively. Ticks in the combination dsRNA (subolesin and enolase) group showed an 80% knockdown. Knockdown of subolesin and enolase resulted in significant depletion in feeding, blood engorgement weight, attachment rate, and egg laying. Silencing of both resulted in a significant (p < 0.05) reduction in tick engorgement, egg laying, egg hatching (15%), and reproduction. CONCLUSIONS AND RELEVANCE: Our results suggest that subolesin and enolase are an exciting target for future tick control strategies.

[A PhD completed. More insight into the origin and composition of salivary stones]. / Serie: Hora est. Meer inzicht in het ontstaan en de samenstelling van speekselstenen.

Salivary stones are hardened, stony calcifications that primarily develop in the drainage duct of a salivary gland. They can lead to obstruction of the saliva flow, resulting in swelling and pain. Since the aetiology of salivary stones remains largely unclear, this was further investigated in this PhD study. A case-control review of patient records showed that systemic diseases and lifestyle factors most likely do not play a role in their occurrence. The biochemical composition of salivary stones removed by oral-maxillofacial surgeons was examined, revealing that large salivary stones have a different inorganic composition than small salivary stones. Several salivary proteins were detected in submandibular salivary stones, including lysozyme, s-IgA, and -amylase. Clumping together of these proteins may play a role in the initial formation of salivary stones.

Insights into the Chemistry, Structure, and Biological Activity of Human Salivary MUC7 Fragments and Their Cu(II) and Zn(II) Complexes.

Mucin 7 (MUC7) is one of the salivary proteins whose role in the innate immune system is widely known, but still, neither its mechanism of action nor the impact of its metal coordination is fully understood. MUC7 and its fragments demonstrate potent antimicrobial activity, serving as a natural defense mechanism for organisms against pathogens. This study delves into the bioinorganic chemistry of MUC7 fragments (L1─EGRERDHELRHRRHHHQSPK; L2─EGRERDHELRHRR; L3─HHHQSPK) and their complexes with Cu(II) and Zn(II) ions. The antimicrobial characteristics of the investigated peptides and their complexes were systematically assessed against bacterial and fungal strains at pH 5.40 and pH 7.40. Our findings highlight the efficacy of these systems against Streptococcus sanguinis, a common oral cavity pathogen. Most interestingly, Zn(II) coordination increased (or triggered) the MUC7 antimicrobial activity, which underscores the pivotal role of metal ion coordination in governing the antimicrobial activity of human salivary MUC7 fragments against S. sanguinis.

Alterations of mannosylated glycopatterns recognized by Hippeastrum hybrid lectin in saliva of patients with lung cancer.

OBJECTIVES: Lung cancer (LC) is the malignant tumor with the highest mortality rate worldwide, and precise early diagnosis can improve patient prognosis. The purpose of this study was to investigate whether alterations in the glycopatterns recognized by the Hippeastrum hybrid lectin (HHL) in salivary proteins are associated with the development of LC. MATERIALS AND METHODS: First, we collected saliva samples from LC (15 lung adenocarcinoma (ADC); 15 squamous cell carcinoma (SCC); 15 small cell lung cancer (SCLC)) and 15 benign pulmonary disease (BPD) for high-throughput detection of abundance levels of HHL-recognized glycopatterns using protein microarrays, and then validated the pooled samples from each group with lectin blotting analysis. Finally, the N-glycan profiles of salivary glycoproteins isolated from the pooled samples using HHL-magnetic particle conjugates were characterized separately using MALDI-TOF/TOF-MS. RESULTS: The results showed that the abundance level of glycopatterns recognized by HHL in salivary proteins was elevated in LC compared to BPD. The proportion of mannosylated N-glycans was notably higher in ADC (31.7%), SCC (39.0%), and SCLC (46.6%) compared to BPD (23.3%). CONCLUSIONS: The altered salivary glycopatterns such as oligomannose, Manα1-3Man, or Manα1-6Man N-glycans recognized by HHL might serve as potential biomarkers for the diagnosis of LC patients. CLINICAL RELEVANCE: This study provides crucial information for studying changes in salivary to differentiate between BPD and LC and facilitate the discovery of biomarkers for LC diagnosis based on precise alterations of mannosylated N-glycans in saliva.

Longitudinal study of the role of salivary proteins on radiation-related caries onset in head and neck cancer patients using 5000 ppm fluoride dentifrice up to one-year post-intensity modulated radiotherapy.

OBJECTIVES: Longitudinal assessment of the role of specific proteins on radiotherapy caries (RC) onset in head and neck cancer patients(HNC) up to one-year post-IMRT using a 5000ppm fluoride paste daily. MATERIALS AND METHODS: Dental status/salivary protein data were obtained from 40 HNC patients pre-IMRT, six months (T1) and 12 months (T2) post-IMRT (ethical approval/consent). DMFT/salivary parameters were quantified, including flow rate, mucin 5B/7, Immunoglobulin A (IgA), cystatin S and α-amylase. RESULTS: 45% patients had at least one carious lesion at T2, a significant reduction in the number of remaining teeth (65% <21), salivary flow rate (< 50%) and, protein secretion (< 0.05) post-IMRT. T1 IgA concentration/secretion rate was associated with RC (p < 0.05). Finally, IgA and total protein concentration obtained at T1 could provide a predictive pattern (AUC 82.3%) for the patients more predisposed to developing RC at T2. CONCLUSIONS: This study demonstrated the significant association of RC with salivary proteins in HNC patients treated with IMRT, revealing the potential role of salivary proteins in the early diagnosis of RC. CLINICAL RELEVANCE: This research contributes to revealing salivary proteins association with RC, and its role in early diagnosis. Therefore, this could be the first step towards personalized medicine approaches to improve this group quality-of-life.

EP300 promotes tumor stemness via epigenetic activation of CRISP3 leading to lobaplatin resistance in triple-negative breast cancer.

Lobaplatin shows antitumor activity against a wide range of tumors, including triple-negative breast cancer (TNBC), and has been linked to cancer stem cell pool. Here, we investigated the molecular mechanisms behind lobaplatin resistance and stemness in vitro and in vivo. Two chemoresistance-related GEO data sets (GSE70690 and GSE103115) were included to screen out relevant genes. Cysteine-rich secretory protein 3 (CRISP3) was found to be overexpressed in lobaplatin-resistant TNBC and related to poor diagnosis. CRISP3 expression was significantly correlated with tumor stemness markers in lobaplatin-resistant cells. E1A-associated protein p300 (EP300) regulated CRISP3 expression by affecting the H3K27ac modification of the CRISP3 promoter. In addition, knocking down EP300 curbed the malignant biological behavior of lobaplatin-resistant cells, which was antagonized by CRISP3 overexpression. Collectively, our results highlight the EP300/CRISP3 axis as a key driver of lobaplatin resistance in TNBC and suggest that therapeutic targeting of this axis may be an effective strategy for enhancing platinum sensitivity in TNBC.

Salivary gland transcriptomics of the cotton aphid Aphis gossypii and comparative analysis with other sap-sucking insects.

Aphids are sap-sucking insects responsible for crop losses and a severe threat to crop production. Proteins in the aphid saliva are integral in establishing an interaction between aphids and plants and are responsible for host plant adaptation. The cotton aphid, Aphis gossypii (Hemiptera: Aphididae) is a major pest of Gossypium hirsutum. Despite extensive studies of the salivary proteins of various aphid species, the components of A. gossypii salivary glands are unknown. In this study, we identified 123,008 transcripts from the salivary gland of A. gossypii. Among those, 2933 proteins have signal peptides with no transmembrane domain known to be secreted from the cell upon feeding. The transcriptome includes proteins with more comprehensive functions such as digestion, detoxification, regulating host defenses, regulation of salivary glands, and a large set of uncharacterized proteins. Comparative analysis of salivary proteins of different aphids and other insects with A. gossypii revealed that 183 and 88 orthologous clusters were common in the Aphididae and non-Aphididae groups, respectively. The structure prediction for highly expressed salivary proteins indicated that most possess an intrinsically disordered region. These results provide valuable reference data for exploring novel functions of salivary proteins in A. gossypii with their host interactions. The identified proteins may help develop a sustainable way to manage aphid pests.

In vivo modification of the enamel pellicle and saliva resveratrol levels after use of resveratrol-containing orodispersible capsules.

OBJECTIVES: To evaluate in vivo 1) the bioavailability of trans-resveratrol when administered through sublingual capsules; 2) the effect of resveratrol on the protein composition of the acquired enamel pellicle (AEP). DESIGN: Ten volunteers received a sublingual capsule containing 50 mg of trans-resveratrol. Unstimulated saliva was then collected after 0, 30, 60, and 120 min and AEP was collected after 120 min following administration of the capsule. In the next week, the volunteers received a placebo sublingual capsule, and saliva and AEP were collected again. Saliva samples were analyzed for free trans-resveratrol using high-performance liquid chromatopgraphy (HPLC), and AEP samples were subjected to proteomic analysis (nLC-ESI-MS/MS). RESULTS: Trans-resveratrol was detected in saliva at all the time points evaluated, with the peak at 30 min. A total of 242 proteins were identified in both groups. Ninety-six proteins were increased and 23 proteins were decreased in the Resveratrol group. Among the up-regulated proteins, isoforms of cystatins, PRPs, Mucin-7, Histatin-1, Lactotrasnferrin and Lysozyme-C were increased and the isoforms of Protein S100, Neutrophil defensins, Albumin, PRPs, and, Statherin were decreased in Resveratrol group. CONCLUSION: The sublingual capsule is effective at increasing the bioavailability of trans-resveratrol in saliva. Several proteins involved in important processes to maintain systemic and oral health homeostasis were identified. These proteins differently expressed due to the presence of trans-resveratrol deserve attention for future studies, since they have important functions, mainly related to antimicrobial action.

Mechanism of complement inhibition by a mosquito protein revealed through cryo-EM.

Salivary complement inhibitors occur in many of the blood feeding arthropod species responsible for transmission of pathogens. During feeding, these inhibitors prevent the production of proinflammatory anaphylatoxins, which may interfere with feeding, and limit formation of the membrane attack complex which could damage arthropod gut tissues. Salivary inhibitors are, in many cases, novel proteins which may be pharmaceutically useful or display unusual mechanisms that could be exploited pharmaceutically. Albicin is a potent inhibitor of the alternative pathway of complement from the saliva of the malaria transmitting mosquito, Anopheles albimanus. Here we describe the cryo-EM structure of albicin bound to C3bBb, the alternative C3 convertase, a proteolytic complex that is responsible for cleavage of C3 and amplification of the complement response. Albicin is shown to induce dimerization of C3bBb, in a manner similar to the bacterial inhibitor SCIN, to form an inactive complex unable to bind the substrate C3. Size exclusion chromatography and structures determined after 30 minutes of incubation of C3b, factor B (FB), factor D (FD) and albicin indicate that FBb dissociates from the inhibited dimeric complex leaving a C3b-albicin dimeric complex which apparently decays more slowly.