In the present study, we hypothesized that HIV-1-induced occult HIV-associated nephropathy (HIVAN) would become apparent in the presence of adverse host factors. To test our hypothesis, Vpr mice (which display doxycycline-dependent Vpr expression in podocytes) with two, three, and four copies of the angiotensinogen (Agt) gene (Vpr-Agt-2, Vpr-Agt-3, and Vpr-Agt-4) were administered doxycycline for 3 weeks (to develop clinically occult HIVAN) followed by doxycycline-free water during the next 3 weeks. Subsequently, renal biomarkers were measured, and kidneys were harvested for renal histology. Vpr-Agt-2 developed neither proteinuria nor elevated blood pressure, and displayed minimal glomerular and tubular lesions only, without any microcyst formation. Vpr-Agt-3 showed mild glomerular and tubular lesions and microcyst formation, whereas Vpr-Agt-4 showed moderate proteinuria, hypertension, glomerular sclerosis, tubular dilation, microcysts, and expression of epithelial mesenchymal transition markers. Vpr-Agt-4 not only displayed enhanced renal tissue expression of Agt, renin, and angiotensin-converting enzyme, but also had higher renal tissue concentrations of angiotensin II. Moreover, renal cells in Vpr-Agt-4 showed enhanced expression of transforming growth factor-β, connective tissue growth factor, and vascular endothelial growth factor. These findings indicate that adverse host factors, such as the activation of the renin-angiotensin system, promote the progression of occult HIVAN to apparent HIVAN.

AT1R has been reported to play an important role in the progression of HIV-associated nephropathy (HIVAN); however, the effect of AT2R has not been studied. Age and sex matched control (FVB/N) and Tg26 mice aged 4, 8, and 16 weeks were studied for renal tissue expression of AT1R and AT2R (Protocol A). Renal tissue mRNA expression of AT2R was lower in Tg26 mice when compared with control mice. In protocol B, Tg26 mice were treated with either saline, telmisartan (TEL, AT1 blocker), PD123319 (PD, AT2R blocker), or TEL + PD for two weeks. TEL-receiving Tg26 (TRTg) displayed less advanced glomerular and tubular lesions when compared with saline-receiving Tg26 (SRTg). TRTgs displayed enhanced renal tissue AT2R expression when compared to SRTgs. Diminution of renal tissue AT2R expression was associated with advanced renal lesions in SRTgs; whereas, upregulation of AT2R expression in TRTgs was associated with attenuated renal lesions. PD-receiving Tg 26 mice (PDRTg) did not show any alteration in the course of HIVAN; whereas, PD + TEL-receiving Tg26 (PD-TRTg) showed worsening of renal lesions when compared to TRTgs. Interestingly, plasma as well as renal tissues of Tg26 mice displayed several fold higher concentration of Ang III, a ligand of AT2R.

In the present study, we evaluated the effect of inhibition of renin activity (aliskiren) on the progression of renal lesions in two different mouse models (Vpr and Tg26) of human immunodeficiency virus (HIV)-associated nephropathy (HIVAN). In protocol A, Vpr mice were fed either water (C-VprA) or doxycycline [Doxy (D-VprA)] in their drinking water for 6 wk. In protocols B and C, Vpr mice received either normal saline (C-VprB/C), Doxy + normal saline (D-VprB/C), or Doxy + aliskiren (AD-VprB/C) for 6 wk ( protocol B) or 12 wk ( protocol C). In protocols D and E, Vpr mice were fed Doxy for 6 wk followed by kidney biopsy. Subsequently, half of the mice were administered either normal saline (D-VprD/E) or aliskiren (AD-VprD/E) for 4 wk ( protocol D) or 8 ( protocol E) wk. All D-VprA mice showed renal lesions in the form of focal segmental glomerular sclerosis and dilatation of tubules. In protocols B and C, aliskiren diminished both progression of renal lesions and proteinuria. In protocol C, aliskiren also diminished ( P < 0.01) the rise in blood urea. In all groups, Doxy-treated mice displayed increased serum ANG I levels (the product of plasma renin activity); on the other hand, all aliskiren-treated mice displayed diminished serum ANG I levels. Renal tissues of D-VprC displayed increased ANG II content; however, aliskiren attenuated renal tissue ANG II production in AD-VprC. In protocol D, AD-VprD showed a 24.2% increase in the number of sclerosed glomeruli compared with 139.2% increase in sclerosed glomeruli in D-VprD ( P < 0.01) from their baseline. The attenuating effect of aliskiren on the progression of renal lesions continued in AD-VprE. Aliskiren also diminished blood pressure, proteinuria, and progression of renal lesions in Tg26 mice. These findings indicate that inhibition of renin activity has a potential to slow down the progression of HIVAN.

During aerobic and anaerobic decomposition of plant and animal reside a complex aggregate of brown to dark coloured amorphous substances is obtained which is called as Humus. It includes humic substances and resynthesizes products of microorganisms. These products are stable and a part of the soil. Humus is categorised according to their molecular weights and solubility into humus, humic acids and fulvic acids. Humic substances are the organic material naturally present in soil. Humic substances positively effect’s soil quality and fertility by increasing its water holding capacity, stabilisation of soil structure, soil microbial activity, plant physiology. It also influence nutrient uptake and root architecture act like phytohormones for phosphorus acquisition, and improving plant adaptation to saline condition. Humus is the primary microhabitat for microorganism such as dictyostelids, myxomycetes, some species of protostelids, members of the genus Copromyxella etc. Other than that auxin like activity of Humic Substances has also been demonstrated in recent studies. The research suggested that it could be the main biological factor that exhibits positive effect on plant physiology. Based on that fertiliser factory also trying to produce are bio- stimulants, based on humic substances and other organic compounds.