UNASSIGNED: Recent advancements reveal saliva as a crucial source of diagnostic biomarkers for various diseases, notably gastric cancer. This systematic review evaluates these biomarkers, emphasizing their clinical applicability and potential in early detection.
UNASSIGNED: An extensive electronic search was conducted across PubMed/MEDLINE, Scopus, and Web of Science to identify relevant studies. Salivary biomarkers were analyzed as independent variables, with gastric cancer as the dependent variable. The study adhered to a protocol registered with PROSPERO (CRD42021259519).
UNASSIGNED: Our analysis identified a range of biomarkers, highlighting three proteins - cystatin-B (CSTB), triosephosphate isomerase (TPI1), and deleted in malignant brain tumors 1 protein (DMBT1) - as particularly accurate for gastric cancer diagnosis.
UNASSIGNED: Salivary biomarkers hold substantial promise for the early detection of gastric cancer. Future research should aim to refine study design and validation for enhancing the quality and applicability of these biomarkers.
UNASSIGNED: Avances recientes revelan la saliva como una fuente crucial de biomarcadores diagnósticos para diversas enfermedades, especialmente el cáncer gástrico. Esta revisión sistemática evalúa estos biomarcadores, con énfasis en su aplicabilidad clínica y potencial para la detección temprana.
UNASSIGNED: Se realizó una extensa búsqueda electrónica en PubMed/MEDLINE, Scopus y Web of Science para identificar estudios relevantes. Los biomarcadores salivales fueron analizados como variables independientes, con el cáncer gástrico como variable dependiente. El estudio siguió un protocolo registrado en PROSPERO (CRD42021259519).
UNASSIGNED: Nuestro análisis identificó una gama de biomarcadores entre los que destacan tres proteínas: cistatina-B (CSTB), triosa fosfato isomerasa (TPI1) y proteína 1 eliminada en tumores cerebrales malignos (DMBT1), como particularmente precisas para el diagnóstico del cáncer gástrico.
UNASSIGNED: : Los biomarcadores salivales tienen un gran potencial para la detección temprana del cáncer gástrico. La investigación futura debería apuntar a refinar el diseño del estudio y la validación para mejorar la calidad y aplicabilidad de estos biomarcadores.

The present systematic review and meta-analysis aimed to assess the association between salivary protein polymorphisms and the risk of periodontal diseases (PD).
The review incorporated cross-sectional, case-control, retrospective/prospective cohort, and randomized controlled trials assessing the influence of salivary protein polymorphisms on the risk of PD development were included in this review.
A thorough literature search was conducted across electronic databases, namely PubMed, Scopus, Embase, and Web of Science, without any restrictions on publication language and year.
A total of 168 studies were identified, of which 19 were eligible for inclusion. The risk of bias (RoB) assessment of the included studies was conducted at the methodological level.
A total of 16 studies were included. Polymorphism in the gene encoding TNF-α was found to be protective against gingivitis, while those encoding IL-1α and IL-1β were associated with developing gingivitis. Of the 42 proteins investigated, various gene polymorphisms were identified as protective or risk factors for periodontitis. Protective genes include CFH, DNMT1, OPRM1, and TLR9. Conversely, certain salivary protein genes (e.g., CRP, ERN1, FAM5C, IDH2, LTA, TET2, MPA, NLRP3, TLR4) were associated with periodontitis risk. Notably, IL6, MMP9, and MUC7 genes showed no association with PD, while MMP13 was linked to early implant loss. Overall, the meta-analysis found a statistically significant association between salivary proteins\' polymorphisms and risk of PD.
Salivary protein polymorphisms significantly influence PD, revealing protective and risk-associated genotypes. Despite limitations, findings suggest therapeutic targets, emphasizing the complex genetics-periodontal health interplay.
This study unveils salivary protein polymorphisms as pivotal factors in PD. Protective genes including CFH and TLR9, and risk-associated genes including CRP and TLR4, indicate a genetic basis for PD susceptibility.

BACKGROUND: Opiorphin has been reported to show a stronger analgesic effect than morphine without causing side effects brought about by morphine-like drugs. Functional opiorphin analogs have been created to enhance its metabolic stability and preserve its potent analgesic effect.
OBJECTIVE: We conducted a systematic review to summarize all opiorphin analogs and identify those with the strongest metabolic stability and antinociceptive effect.
METHODS: From a total of 122 articles, 11 made it to the quantitative synthesis phase. The included articles were categorized into the type of modifications used to improve the metabolic stability of the peptide, metabolism and toxicity profile, drug absorption and in vitro cytotoxicity, anti-nociceptive effect, the opiorphin analogs\' administration in animals or humans, and the type of the test used to test the antinociceptive effect.
RESULTS: The substitution of natural amino acid with a non-natural amino acid, side-chain modifications, or D-aminoacid substitution were the most used type of peptide modification to create opiorphin analogs. STR-324 and PEGylated liposomes loaded with opiorphin showed the best metabolism and toxicity performance. [C]-[(CH2)6]-QRF-[S-O-(CH2)8]-R showed high stability in human plasma and stronger inhibitory potency. YQRFSR and PEGylated liposomes loaded with opiorphin showed a stronger antinociceptive effect than the parent opiorphin or morphine, with an analgesic effect of PEGylated liposomes lasting more than 50%. Intravenous administration was the preferred method of opiorphin analog administration, and different tests were used to test the antinociceptive effect.
CONCLUSIONS: This paper presents the first systematic review discussing opiorphin and opiorphin analogs and identifies the most promising candidates for future research.

BACKGROUND: There have been many studies on MUC7 and bladder cancer (BC) that have been published; however, all sample sizes were not enough which led to their conclusions being based on small samples. Therefore, this meta-analysis aims to systematically analyze the diagnostic value of MUC7 for bladder cancer and provide a scientific basis for the diagnosis of bladder cancer.
METHODS: To obtain relevant literature on MUC7 diagnosed bladder cancer, databases such as PubMed, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wanfang data, Chongqing VIP, and Chinese Biomedical Literature Database were searched from the establishment of the database to July 11, 2023. According to established inclusion and exclusion criteria, literature was screened and data were extracted. The Quality Assessment of Diagnostic Accuracy Studies 2 was used to evaluate the risk of bias and applicability of included literature. Meta-disc1.4 and Stata12.0 software were used for Meta-analysis.
RESULTS: Twelve studies were included, including728 BC patients and 458 non-BC controls. The pooled sensitivity and pooled specificity were 0.74 (95% confidence interval [CI]: 0.71-0.77) and 0.92 (95% CI: 0.90-0.95), respectively. The pooled negative likelihood ratio was 0.27 (95% CI: 0.20-0.36), and the pooled positive likelihood ratio was 9.58 (95% CI: 5.40-17.00). The diagnostic odds ratio was 40.95 (95% CI: 20.31-82.59), and the area under the curve was 0.91 in the overall summary of the receiver operating characteristic curve.
CONCLUSIONS: MUC7 might be a potential biomarker for diagnosing BC. However, more large sample and multicenter studies are needed to prove whether it can be used in clinical diagnosis.

Oral squamous cell carcinoma (OSCC) is an aggressive malignancy with increased mortality, in which the early diagnosis is the most important step in increasing patients\' survival rate. Extensive research has evaluated the role of saliva as a source of diagnostic biomarkers, among which matrix metalloproteinases (MMPs) have shown a valuable potential for detecting even early stages of OSCC. The aim of this review was to present recent clinical data regarding the significance of salivary MMPs in the detection of early malignant transformation of the oral mucosa. A narrative review was conducted on articles published in PubMed, Cochrane Library, Web of Science, EBSCO and SciELO databases, using specific terms. Our search revealed that MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, MMP-10, MMP-12 and MMP-13 had significantly higher levels in saliva from patients with OSCC compared to controls. However, the strength of evidence is limited, as most information regarding their use as adjuvant diagnostic tools for OSCC comes from studies with a low number of participants, variable methodologies for saliva sampling and diagnostic assays, and insufficient adjustment for all covariates. MMP-1, MMP-3 and MMP-9 were considered the most promising candidates for salivary diagnosis of OSCC, but larger studies are needed in order to validate their clinical application.

Dental caries is a multifactorial chronic disease resulting from the intricate interplay among acid-generating bacteria, fermentable carbohydrates, and several host factors such as saliva. Saliva comprises several proteins which could be utilized as biomarkers for caries prevention, diagnosis, and prognosis. Mass spectrometry-based salivary proteomics approaches, owing to their sensitivity, provide the opportunity to investigate and unveil crucial cariogenic pathogen activity and host indicators and may demonstrate clinically relevant biomarkers to improve caries diagnosis and management. The present review outlines the published literature of human clinical proteomics investigations on caries and extensively elucidates frequently reported salivary proteins as biomarkers. This review also discusses important aspects while designing an experimental proteomics workflow. The protein-protein interactions and the clinical relevance of salivary proteins as biomarkers for caries, together with uninvestigated domains of the discipline are also discussed critically.

Salivary proteins play an important role in repairing mechanisms of damaged tissues and the maintenance of oral health. However, there is a dearth of information in the literature regarding the concentrations of salivary proteins in caries-free (CF) and caries-active (CA) subjects. Hence, this systematic review was conducted to update our previous systematic review published in 2013 that aimed to assess the association between caries and salivary proteins by comparing CF and CA individuals. Thereby, evaluating the possibility of whether salivary proteins can be regarded as biomarkers for caries. An extensive search of studies was conducted using PubMed, EMBASE, Clarivate Analytics\' Web of Science, and Elsevier\'s Scopus between July 2012 and January 2022, without any language restriction. Manual searching in Google Scholar and evaluation of bibliographies of the included studies were also undertaken. The Newcastle-Ottawa Scale was used to assess the risk of bias (RoB) within the included studies. Of 22 included studies, 1,551 human subjects (range: 30-213 participants) were recruited, of which 848 individuals (54.7%) were CA and 703 (45.3%) were CF. Regarding the utilization of DMFT as the caries index, high variability was observed across different articles. A statistically significant increase in the salivary levels of alpha-amylase, acidic proline-rich protein-1, histatin-5, lactoperoxidase, and mucin-1 was found in CA patients, while the salivary levels of carbonic anhydrase 6, proteinase-3, and statherin were observed to be significantly increased in CF subjects. Conflicting results were found regarding the salivary levels of immunoglobulin A and total proteins among CA and CF subjects. The included studies were categorized as low RoB (n = 15), medium RoB (n = 4), and high RoB (n = 3). Due to significant heterogeneity among the included studies, no meta-analysis could be performed. In conclusion, the salivary levels of protein(s) might be a useful biomarker for caries diagnosis, especially alpha-amylase, acidic proline-rich protein-1, histatin-5, lactoperoxidase, mucin-1, carbonic anhydrase 6, proteinase-3, and statherin. However, their diagnostic value must be verified by large-scale prospective studies.

OBJECTIVE: To assess the relationship between salivary biomarkers of oxidative stress and dental caries in children.
METHODS: Studies conducted in children up to 12 years old comparing salivary biomarkers of oxidative stress such as malondialdehyde (MDA), superoxide dismutase (SOD), uric acid, and total antioxidant capacity (TAC), considering children with dental caries lesions and caries-free ones were selected. In addition, salivary parameters such as salivary flow, pH, buffering capacity, calcium and total protein levels were evaluated. A systematic literature review was carried out in 8 databases. The standardized mean difference (SMD) was measured using inverse variance as a statistical method and random effects as an analysis model, corresponding to a 95% confidence interval (CI).
RESULTS: The TAC levels were higher in children affected by dental caries compared to caries-free ones (control group), regardless of age (SMD 2.66, CI 1.33, 3.98), or gender (SMD 0.98, CI 0.56, 1.39). When adjusted for normalized protein, MDA levels were lower in the dental caries group than in the control group (SMD -16.51, CI -29.02, -4.00), and SOD levels were higher in the dental caries group (SMD 5.09, CI 0.01.10.18). The total protein concentration in saliva of children with dental caries was higher than in the control group, regardless of age (SMD 0.98, CI 0.27, 1.69), or gender (SMD 0.77, CI 0.45, 1.10). The salivary parameters assessed had lower levels in children affected by dental caries (p < 0.05).
CONCLUSIONS: The levels of oxidative stress biomarkers and salivary parameters are altered in saliva of children with dental caries.

Entomological surveillance for malaria is inherently resource-intensive and produces crude population-level measures of vector exposure which are insensitive in low-transmission settings. Antibodies against Anopheles salivary proteins measured at the individual level may serve as proxy biomarkers for vector exposure and malaria transmission, but their relationship is yet to be quantified.
A systematic review of studies measuring antibodies against Anopheles salivary antigens (PROSPERO: CRD42020185449). Multilevel modelling (to account for multiple study-specific observations [level 1], nested within study [level 2], and study nested within country [level 3]) estimated associations between seroprevalence with Anopheles human biting rate (HBR) and malaria transmission measures.
From 3981 studies identified in literature searches, 42 studies across 16 countries were included contributing 393 study-specific observations of anti-Anopheles salivary antibodies determined in 42,764 samples. A positive association between HBR (log transformed) and seroprevalence was found; overall a twofold (100% relative) increase in HBR was associated with a 23% increase in odds of seropositivity (OR: 1.23, 95% CI: 1.10-1.37; p<0.001). The association between HBR and Anopheles salivary antibodies was strongest with concordant, rather than discordant, Anopheles species. Seroprevalence was also significantly positively associated with established epidemiological measures of malaria transmission: entomological inoculation rate, Plasmodium spp. prevalence, and malarial endemicity class.
Anopheles salivary antibody biomarkers can serve as a proxy measure for HBR and malaria transmission, and could monitor malaria receptivity of a population to sustain malaria transmission. Validation of Anopheles species-specific biomarkers is important given the global heterogeneity in the distribution of Anopheles species. Salivary biomarkers have the potential to transform surveillance by replacing impractical, inaccurate entomological investigations, especially in areas progressing towards malaria elimination.
Australian National Health and Medical Research Council, Wellcome Trust.

Sjögren\'s syndrome (SS) is a chronic autoimmune disease characterized by dry mouth and dry eyes, with lymphocytic infiltration of the exocrine glands. Saliva is becoming a useful tool to determine the clinical and pathological characteristics of SS because the collection method is easy and non-invasive. Since 1900, salivary proteomic analysis has been performed continuously using a variety of optimized analytical methods. Many studies have identified distinct characteristics of salivary proteins in patients with primary SS, and the changes were related to chronic inflammation and overproduction of immunoglobulins or downregulated secretory function. Several proteomic studies using whole or parotid saliva have evaluated whether several salivary proteins can be used to discriminate SS, including salivary β2-microglobulin, calprotectin, carbonic anhydrase VI, neutrophil gelatinase-associated lipocalin, sialic acid-binding immunoglobulin-like lectin-5, and tripartite motif-containing protein 29. In addition, salivary proinflammatory cytokine levels have been reported to be increased in patients with SS. Although these candidate salivary proteins have exhibited considerable differences in patients with SS, more data are needed to confirm their role as biomarkers. Moreover, the identification of salivary characteristics that can accurately reflect disease activity, predict treatment response and prognosis, and diagnose SS is anticipated.