The role of lymphoid tissue SPARC in the pathogenesis and response to treatment of multiple myeloma.

BACKGROUND: Despite the significant progress in the treatment of multiple myeloma (MM), the disease remains untreatable and its cure is still an unmet clinical need. Neoplastic transformation in MM is initiated in the germinal centers (GCs) of secondary lymphoid tissue (SLT) where B cells experience extensive somatic hypermutation induced by follicular dendritic cells (FDCs) and T-cell signals. OBJECTIVE: We reason that secreted protein acidic and rich in cysteine (SPARC), a common stromal motif expressed by FDCs at the origin (SLTs) and the destination (BM) of MM, plays a role in the pathogenesis of MM, and, here, we sought to investigate this role. METHODS: There were 107 BM biopsies from 57 MM patients (taken at different time points) together with 13 control specimens assessed for SPARC gene and protein expression and compared with tonsillar tissues. In addition, regulation of myeloma-promoting genes by SPARC-secreting FDCs was assessed in in vitro GC reactions (GCRs). RESULTS: SPARC gene expression was confirmed in both human primary (BM) and secondary (tonsils) lymphoid tissues, and the expression was significantly higher in the BM. Sparc was detectable in the BM and tonsillar lysates, co-localized with the FDC markers in both tissues, and stimulation of FDCs in vitro induced significantly higher levels of SPARC expression than unstimulated controls. In addition, SPARC inversely correlated with BM PC infiltration, ISS staging, and ECOG performance of the MM patients, and in vitro addition of FDCs to lymphocytes inhibited the expression of several oncogenes associated with malignant transformation of PCs. CONCLUSION: FDC-SPARC inhibits several myelomagenic gene expression and inversely correlates with PC infiltration and MM progression. Therapeutic induction of SPARC expression through combinations of the current MM drugs, repositioning of non-MM drugs, or novel drug discovery could pave the way to better control MM in clinically severe and drug-resistant patients

First Report of Meloidogyne enterolobii Yang & Eisenback, 1983 (Guava Root-knot Nematode) Infecting Guava (Psidium guajava) in Egypt

Meloidogyne enterolobii Yang & Eisenback, 1983 (guava root-knot nematode) is an important disease in subtropical to tropical climate in several areas of the world (Subbotin et al., 2021). It is a highly polyphagous root-knot nematode species causing major damage to a range of economically important crops. The expansion of this species is increasing worldwide creating a potential problem to the maintenance of resistance genes to other major Meloidogyne species (Castagnone-Sereno and Castillo, 2020). Additionally, the diagnosis of M. enterolobii can be challenging due to morphological similarities with other root-knot nematode species (Castagnone-Sereno, 2012). In the African continent, it has been cited in several countries of Equatorial and South Africa (Subbotin et al., 2021), but not in North Africa. Two guava groves (at Bany Salama, Natrn vally, El Beheira governorate, 30.322043N, 30.518529E; and Izbat Al Halawijah, Monshaah Alaweyah, Abu El Matamir, El Beheira governorate 30.9398050N, 30.1484430E), in Egypt, were found with significant symptoms of tree decline and root galling damage. The presence of egg masses and females of root-knot nematodes were found inside the galls (Figure 1A, B). Nematodes were extracted from soil samples with levels of 12300 and 12600 second-stage juveniles (J2s)/250 g of soil using a modified Baerman method (Hooper, 1986), respectively. Nematode root density was 24367 eggs/g of root, using the protocol described in Hussey and Barker (1973) for Izbat Al Halawijah population. For morphological and morphometrical identification, J2s and females were fixed using a hot formalin solution (4% v/v). DNA was isolated from single J2s specimen for: i) testing multiplex specific-PCR assay for M. incognita, M. javanica and M. arenaria (Kiewnick et al., 2013), and ii) amplifying and sequencing of cytochrome oxidase subunit II (COII) and the 16S rRNA mitochondrial region using the primer pair C2F3 (5'-GGTCAATGTTCAGAAATTTGTGG-3') (Powers and Harris, 1993) and MRH106 (5'- AATTTCTAAAGACTTTTCTTAGT-3') (Stanton et al., 1997). Perineal patterns of females for Izbat Al Halawijah population were typical of the species (Fig. 1D), body size (L: 520-774 µm; W: 214-487 µm), stylet length (12.5-13.7 µm) and ratio from distance from anterior end to excretory pore and stylet length (4.2) in females (n = 18), fitting with original description and others (Subbotin et al., 2021). J2s from Izbat Al Halawijah population (n=13) (Fig. 1C, E-H) showed: body length (393.5-475 µm), stylet length (11.5-13.5), excretory pore to anterior end (89-95.5 µm), tail length (50.0-60.0 µm), tail hyaline region (12.0-21.0 µm), a ratio (24.2-32.5), b ratio (4.9-6.5), c ratio (7.3-8.6) and c' (5.0-6.4), also fitting with original description and others (Subbotin et al., 2021). Specific PCR did not amplify any band (Kiewnick et al., 2013). Four J2s individuals were sequenced for COII-16S rRNA region for each population showing M. enterolobii as unique species and without intraspecific variability. Two identical DNA fragments of 814 bp obtained for both populations (OP434400 and OP434401) were compared with those in GenBank. A BLAST search indicated the sequences were 100% identical to several sequences of M. enterolobii (MF467278 and KX823371). On the basis of these results, the root-knot nematodes isolated from these two guava groves in Egypt were confirmed as M. enterolobii. This is a well-known pathogen of guava, causing important losses in this crop (Castagnone-Sereno and Castillo, 2020) and it is regulated as quarantine nematode in the Mediterranean region (EPPO).Peer reviewe