UNASSIGNED: Tests capable of accurate prediction of spontaneous preterm birth (sPTB) are crucial to inform clinical decisions to prevent neonatal deaths and reduce the risk of morbidity in surviving infants. A systematic literature review and meta-analysis were performed to assess the utility of the quantitative fetal fibronectin (fFN) test to predict sPTB at different test concentration thresholds.
UNASSIGNED: Literature searches were conducted in MEDLINE, Embase, and the Cochrane Library in May 2022. Observational studies and clinical trials investigating the clinical utility of the quantitative fFN test in asymptomatic pregnancies prior to 37 weeks of gestation were eligible for inclusion. Meta-analysis quantified the risk of sPTB prior to four gestational age milestones (<28, <30, <34 and <37 weeks) based on quantitative fFN levels. No risk of bias assessment was performed however, clinical and methodological heterogeneity was explored to determine the feasibility of performing analyses.
UNASSIGNED: 11 studies showed a quantitative assessment of fFN can differentiate between very high and very low risks of sPTB in asymptomatic pregnancies with <10% of women with very low fFN (<10 ng/mL) versus 37-67% of women with very high fFN (>200 ng/mL) delivering before 34 weeks. A meta-analysis of two studies showed, albeit with a low number of events, the odds of sPTB prior to 28 weeks was nine times higher in women testing positive at ≥50 ng/mL, whereas the odds of sPTB was 25 times higher in women with fFN concentrations >200 ng/mL (versus <50 ng/mL reference). Similarly, pooling three studies showed the odds of sPTB prior to 37 weeks was four times higher in women who tested positive at ≥50 ng/ml whereas the odds of delivery before 37 weeks was seven times higher for women with fFN concentrations ≥200 ng/ml (versus <50 ng/mL reference).
UNASSIGNED: Quantitative fFN testing demonstrates increased predictive capabilities and utility of fFN testing in clinical practice, potentially preventing unnecessary intervention for women at very low risk and allowing an opportunity to optimize the management of asymptomatic patients at high risk of preterm delivery.

Metabolism of fibronectin, the protein that plays a key role in the healing of wounds, is changed in the patients with diabetes mellitus. Fibronectin can interact with other proteins and proteoglycans and organise them to form the extracellular matrix, the basis of the granulation tissue in healing wounds. However, diabetic foot ulcers (DFUs) suffer from inadequate deposition of this protein. Degradation prevails over fibronectin synthesis in the proteolytic inflammatory environment in the ulcers. Because of the lack of fibronectin in the wound bed, the assembly of the extracellular matrix and the deposition of the granulation tissue cannot be started. A number of methods have been designed that prevents fibronectin degradation, replace lacking fibronectin or support its formation in non-healing wounds in animal models of diabetes. The aim of this article is to review the metabolism of fibronectin in DFUs and to emphasise that it would be useful to pay more attention to fibronectin matrix assembly in the ulcers when laboratory methods are translated to clinical practice.

UNASSIGNED: The potential for cartilage repair using articular cartilage derived chondroprogenitors has recently gained popularity due to promising results from in-vitro and in-vivo studies. Translation of results from in-vitro to a clinical setting requires a sufficient number of animal studies displaying significant positive outcomes. Thus, this systematic review comprehensively discusses the available literature (January 2000-March 2022) on animal models employing chondroprogenitors for cartilage regeneration, highlighting the results and limitations associated with their use.As per Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a web-based search of PubMed and SCOPUS databases was performed for the following terminologies: \"chondroprogenitors\", \"cartilage-progenitors\", and \"chondrogenic-progenitors\", which yielded 528 studies. A total of 12 studies met the standardized inclusion criteria, which included chondroprogenitors derived from hyaline cartilage isolated using fibronectin adhesion assay (FAA) or migratory assay from explant cultures, further analyzing the role of chondroprogenitors using in-vivo animal models.
UNASSIGNED: Analysis revealed that FAA chondroprogenitors demonstrated the ability to attenuate osteoarthritis, repair chondral defects and form stable cartilage in animal models. They displayed better outcomes than bone marrow-derived mesenchymal stem cells but were comparable to chondrocytes. Migratory chondroprogenitors also demonstrated superiority to BM-MSCs in terms of higher chondrogenesis and lower hypertrophy, although a direct comparison to FAA-CPs and other cell types is warranted.
UNASSIGNED: Chondroprogenitors exhibit superior properties for chondrogenic repair; however, limited data on animal studies necessitates further studies to optimize their use before clinical translation for neo-cartilage formation.

Human papillomaviruses (HPVs) are common sexually transmitted infectious agents responsible for several anogenital and head and neck cancers. Cervical cancer (CC) is the fourth leading cause of death in women with cancer. The progression of a persistent HPV infection to cancer takes 15-20 years and can be preventable through screening. Cervical cytology (Pap smear) is the standard screening test for CC and precancerous lesions. For ASC-US and ASC-H lesions, a combination of Pap smear and HR-HPV analysis is recommended as a triage step before colposcopy. However, these tests cannot predict progression to CC. For this purpose, we summarized current scientific data on the role of p16/Ki-67 immunohistostaining, telomerase and fibronectin in predicting progression to CC. p16 and p16/Ki-67 dual staining (DS) were more specific than HR-HPV DNA testing for the detection of CIN2+/CIN3+ in women with ASC-US and LSIL. Similarly, hTERC FISH analysis significantly improved the specificity and positive predictive value of HPV DNA testing in differentiating CIN2+ from CIN2 cytological samples. In conclusion, p16 IHC, p16/Ki-67 DS and hTERC FISH amplification are all valid adjunctive biomarkers which significantly increase the sensitivity and specificity of cervical dysplasia diagnosis, especially when combined with HPV DNA testing. However, considering the global socioeconomic background, we can postulate that p16 and p16/ Ki-67 IHC can be used as a next step after positive cytology for ASC-US or LSIL specimens in low-income countries, instead of HPV DNA testing. Alternatively, if HPV DNA testing is covered by insurance, p16 or p16/Ki-67 DS and HPV DNA co-testing can be performed. In middle- and high-income countries, hTERC amplification can be performed as an adjunctive test to HPV DNA testing in women with ASC-US and LSIL.

Biological tissues are not uniquely composed of cells. A substantial part of their volume is extracellular space, which is primarily filled by an intricate network of macromolecules constituting the extracellular matrix (ECM). The ECM serves as the scaffolding for tissues and organs throughout the body, playing an essential role in their structural and functional integrity. Understanding the intimate interaction between the cells and their structural microenvironment is central to our understanding of the factors driving the formation of normal versus remodelled tissue, including the processes involved in chronic fibrotic diseases. The visualization of the ECM is a key factor to track such changes successfully. This review is focused on presenting several optical imaging microscopy modalities used to characterize different ECM components. In this review, we describe and provide examples of applications of a vast gamut of microscopy techniques, such as widefield fluorescence, total internal reflection fluorescence, laser scanning confocal microscopy, multipoint/slit confocal microscopy, two-photon excited fluorescence (TPEF), second and third harmonic generation (SHG, THG), coherent anti-Stokes Raman scattering (CARS), fluorescence lifetime imaging microscopy (FLIM), structured illumination microscopy (SIM), stimulated emission depletion microscopy (STED), ground-state depletion microscopy (GSD), and photoactivated localization microscopy (PALM/fPALM), as well as their main advantages, limitations.

Fibronectin (FN) circulating in the blood and produced by cells provides the basis of the extracellular matrix (ECM) formed in healing acute wounds. The time-dependent deposition of FN by macrophages, its synthesis by fibroblasts and myofibroblasts, and later degradation in the remodeled granulation tissue are a prerequisite for successful healing of wounds. However, the pattern of FN expression and deposition in skin lesions is disturbed. The degradation of the ECM components including FN in varicose veins prevails over ECM synthesis and deposition. FN is inconspicuous in the fibrotic lesions in lipodermatosclerosis, while tenascin-C containing FN-like peptide sequences are prominent. FN is produced in large amounts by fibroblasts at the edge of venous ulcers but FN deposition at the wound bed is impaired. Both the proteolytic environment in the wounds and the changed function of the ulcer fibroblasts may be responsible for the poor healing of venous ulcers. The aim of this review is to describe the current knowledge of FN pathophysiology in chronic venous diseases. In view of the fact that FN plays a crucial role in organizing the ECM, further research focused on FN metabolism in venous diseases may bring results applicable to the treatment of the diseases.

OBJECTIVE: Chondroprogenitors have recently gained prominence due to promising results seen in in vitro and animal studies as a potential contender in cell-based therapy for cartilage repair. Lack of consensus regarding nomenclature, isolation techniques, and expansion protocols create substantial limitations for translational research, especially given the absence of distinct markers of identification. The objective of this systematic review was to identify and collate information pertaining to hyaline cartilage-derived chondroprogenitors, with regard to their isolation, culture, and outcome measures.
METHODS: As per Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a web-based search of Scopus and PubMed databases was performed from January 2000 to May 2020, which yielded 509 studies. A total of 65 studies were identified that met the standardized inclusion criteria which comprised of, but was not limited to, progenitors derived from fibronectin adhesion, migrated subpopulation from explant cultures, and single-cell sorting.
RESULTS: Literature search revealed that progenitors demonstrated inherent chondrogenesis and minimal tendency for hypertrophy. Multiple sources also demonstrated significantly better outcomes that bone marrow-derived mesenchymal stem cells and comparable results to chondrocytes. With regard to progenitor subgroups, collated evidence points to better and consistent outcomes with the use of migratory progenitors when compared to fibronectin adhesion assay-derived progenitors, although a direct comparison between the two cell populations is warranted.
CONCLUSIONS: Since chondroprogenitors exhibit favorable properties for cartilage repair, efficient characterization of progenitors is imperative, to complete their phenotypic profile, so as to optimize their use in translational research for neocartilage formation.

Persistent corneal epithelial defects (PEDs or PCEDs) result from the failure of rapid re-epithelialization and closure within 10-14 days after a corneal injury, even with standard supportive treatment. Disruptions in the protective epithelial and stromal layers of the cornea can render the eye susceptible to infection, stromal ulceration, perforation, scarring, and significant vision loss. Although several therapies exist and an increasing number of novel approaches are emerging, treatment of PEDs can still be quite challenging. It is important to treat the underlying causative condition, which may include an infection, limbal stem cell deficiency, or diabetes, in order to facilitate wound healing. Standard treatments, such as bandage contact lenses (BCLs) and artificial tears (ATs), aim to provide barrier protection to the epithelial layer. Recently-developed medical treatments can target the re-epithelialization process by facilitating access to growth factors and anti-inflammatory agents, and novel surgical techniques can provide re-innervation to the cornea. PEDs should be treated within 7-10 days to avoid secondary complications. These interventions, along with a step-wise approach to management, can be useful in patients with PEDs that are refractory to standard medical treatment. In this review, we discuss the epidemiology, etiology, diagnosis, current and novel management, and prognosis of persistent epithelial defects.

OBJECTIVE: To identify all systematic reviews investigating the role of maternal and fetal biomarkers for predicting spontaneous preterm birth (SPTB).
METHODS: Medline and Web of Sciences databases were searched electronically. Studies exploring the association between maternal biomarkers and spontaneous delivery were considered suitable for inclusion. A synthesis of the systematic reviews was performed with the umbrella methodology. Statistical measures of association (Odd ratio, OR, relative risk, RR) and predictive accuracy (sensitivity, specificity, positive and negative likelihood ratios were used to synthesize results of the included studies.
RESULTS: 21,614 articles were identified, 542 were assessed with respect to their eligibility for inclusion and 14 systematic reviews included. Cervical fibronectin was the biomarkers which showed the highest strength of association with the occurrence of SPTB (delivery within 24 h OR 7, 95%CI 3-17; delivery <7 days (OR 12, 95%CI 8-16). Maternal serum alpha fetoprotein, was associated with an OR of 4 and 3 for early and late SPTB. C-reactive protein had an OR of 2 (95%CI 1-2) and 8 (95%CI 4-16) when detected in maternal plasma and amniotic fluid, respectively. Among cytokines, interleukin-6 had an OR and an LR + for SPTB of 2 and 12 when detected in maternal serum.
CONCLUSIONS: Cervical fetal fibronectin, alpha fetoprotein, C- reactive protein and interleukin 6 can have an overall good diagnostic accuracy in identifying pregnancies at risk of SPTB. Large prospective studies in different sub-set of women are needed to ascertain whether the combination of different serological and imaging marker can improve antenatal prediction of this condition.

The extracellular matrix (ECM) plays a key role in the modulation of cancer cell invasion. In urothelial carcinoma of the bladder (UC) the role of ECM proteins has been widely studied. The mechanisms, which are involved in the development of invasion, progression and generalization, are complex, depending on the interaction of ECM proteins with each other as well as with cancer cells. The following review will focus on the pathogenetic role and prognostic value of structural proteins, such as laminins, collagens, fibronectin (FN), tenascin (Tn-C) and thrombospondin 1 (TSP1) in UC. In addition, the role of integrins mediating the interaction of ECM molecules and cancer cells will be addressed, since integrin-mediated FN, Tn-C and TSP1 interactions seem to play an important role during tumor cell invasion and angiogenesis.